Rada Savic, PhD

Co-Vice Dean of Graduate Pharmacy Education Programs
Professor
Department of Bioengineering and Therapeutic Sciences
Savic
[email protected]
Phone: +1 415 502-0640
1700 4th St, Rm 503C
UCSF Box 2552
San Francisco, CA 94158
United States

Links

Savic Lab UCSF Profiles Division of Clinical Pharmacology & Experimental Therapeutics

Affiliations

Education programs

Pharmaceutical Sciences and Pharmacogenomics Graduate Program (PSPG)

UCSF centers, institutes, and research programs

Quantitative Biosciences Institute (QBI)

What I do

I co-lead the School’s plans for developing graduate education programs in the computational and experimental sciences, along with Brian Shoichet, PhD. These programs are geared toward giving the School’s PharmD students greater career opportunities throughout biomedicine.

As a faculty member in the Department of Bioengineering and Therapeutic Sciences, I investigate optimal drug discovery and development approaches using computational methods. I integrate data and knowledge to determine the optimal choices of precise and personalized treatments.

Departmental research area

drug development and regulatory sciences
computational biology and systems pharmacology

My research expertise

Pharmacometrics, precision dosing, clinical pharmacology, systems pharmacology, precision medicine, pharmacogenetics, translational sciences, nonlinear mixed effects models, Infectious diseases, tuberculosis, malaria, HIV cure, developmental pharmacology, disease progression models, drug development, NONMEM, modeling and simulations, clinical trial design, pediatrics, pharmacokinetics, pharmacodynamics, data science

Professional background

Degrees

PhD, Pharmacometrics, Uppsala University, Uppsala, Sweden, 2008
MS, Biomedical Sciences, Uppsala University, Uppsala, Sweden, 2004
BSc, Pharmacy, University of Belgrade, Serbia, 2003

Biography

My research uses computational methods to study the dynamic interplay between disease progression, treatment regimen, and drug and biomarker response across relevant scales (molecule, cell, tissue, organ & whole body) to determine causal links underlying variability in (safety and efficacy) clinical outcomes. By integrating multi-scale, and multi-level clinical data, we aim to determine the right dose, schedule, and treatment duration of various therapies, potentially bringing novel, precise and personalized treatment options to patients with unmet need more quickly.

Research keywords

  • Nonlinear mixed effects models
  • Pyrazinamide
  • quantitative pharmacology
  • tuberculosis
  • Meningeal
  • Infectious diseases
  • Precision Dosing
  • precision medicine
  • Pulmonary
  • HIV Cure
  • Data Science
  • Pregnancy Complications
  • Parasitic
  • Antitubercular Agents
  • Developmental Pharmacology
  • Quinolines
  • Rifampin
  • Systems Pharmacology
  • malaria
  • pharmacology
  • clinical
  • Drug Dosage Calculations
  • Isoniazid
  • Pharmacometrics
  • Translational Sciences
  • Disease progression models
  • clinical pharmacology
  • Artemisinins
  • pharmacogenetics
  • antibiotics
  • Antitubercular
  • Multidrug-Resistant
  • Multiple sclerosis
  • pharmacokinetics
  • tuberculosis
  • Rifampin
  • Isoniazid
  • Latent Tuberculosis
  • Pyrazinamide
  • Pregnancy Complications, Parasitic
  • Tuberculosis, Pulmonary
  • Tuberculosis, Multidrug-Resistant
  • Antibiotics, Antitubercular
  • Artemisinins
  • pharmacokinetics
  • Antimalarials
  • Mycobacterium tuberculosis
  • Antitubercular Agents
  • Quinolines

Publications

Ali AM, Wallender E, Hughes E, Dorsey G, Savic RM. Interplay among malnutrition, chemoprevention, and the risk of malaria in young Ugandan children: Longitudinal pharmacodynamic and growth analysis. CPT Pharmacometrics Syst Pharmacol. 2023 Mar 14.
Solans BP, Béranger A, Radtke K, Mohamed A, Mirzayev F, Gegia M, Linh NN, Schumacher SG, Nahid P, Savic RM. Effectiveness and pharmacokinetic exposures of first-line drugs used to treat drug-susceptible tuberculosis in children: a systematic review and meta-analysis. Clin Infect Dis. 2023 Jan 04.
Chang V, Phillips PPJ, Imperial MZ, Nahid P, Savic RM. A comparison of clinical development pathways to advance tuberculosis regimen development. BMC Infect Dis. 2022 Dec 09; 22(1):920.
Garcia-Cremades M, Vucicevic K, Hendrix CW, Jayachandran P, Jarlsberg L, Grant R, Celum CL, Martin M, Baeten JM, Marrazzo J, Anderson P, Choopanya K, Vanichseni S, Glidden DV, Savic RM. Characterizing HIV-Preventive, Plasma Tenofovir Concentrations-A Pooled Participant-level Data Analysis From Human Immunodeficiency Virus Preexposure Prophylaxis Clinical Trials. Clin Infect Dis. 2022 11 30; 75(11):1873-1882.
Hughes JA, Solans BP, Draper HR, Schaaf HS, Winckler JL, van der Laan L, Radtke KK, Fourie B, Wiesner L, Hesseling AC, Savic RM, Garcia-Prats AJ. Pharmacokinetics and Safety of Bedaquiline in Human Immunodeficiency Virus (HIV)-Positive and Negative Older Children and Adolescents With Rifampicin-Resistant Tuberculosis. Clin Infect Dis. 2022 11 14; 75(10):1772-1780.
Béranger A, Bekker A, Solans BP, Cotton MF, Mirochnick M, Violari A, Wang J, Cababasay M, Wiesner L, Browning R, Moye J, Capparelli EV, Savic RM. Influence of NAT2 Genotype and Maturation on Isoniazid Exposure in Low-Birth-Weight and Preterm Infants With or Without Human Immunodeficiency Virus (HIV) Exposure. Clin Infect Dis. 2022 09 29; 75(6):1037-1045.
Hughes E, Wallender E, Kajubi R, Jagannathan P, Ochieng T, Kakuru A, Kamya MR, Clark TD, Rosenthal PJ, Dorsey G, Aweeka F, Savic RM. Piperaquine-Induced QTc Prolongation Decreases With Repeated Monthly Dihydroartemisinin-Piperaquine Dosing in Pregnant Ugandan Women. Clin Infect Dis. 2022 08 31; 75(3):406-415.
Fox WS, Strydom N, Imperial MZ, Jarlsberg L, Savic RM. Examining nonadherence in the treatment of tuberculosis: The patterns that lead to failure. Br J Clin Pharmacol. 2022 Aug 29.
Garcia-Cremades M, Hendrix CW, Jayachandran P, Strydom N, Jarlsberg L, Grant R, Celum CL, Martin M, Baeten JM, Marrazzo J, Anderson P, Choopanya K, Vanichseni S, Glidden DV, Savic RM. Modeling the Probability of HIV Infection over Time in High-Risk Seronegative Participants Receiving Placebo in Five Randomized Double-Blind Placebo-Controlled HIV Pre-Exposure Prophylaxis Trials: A Patient-Level Pooled Analysis. Pharmaceutics. 2022 Aug 27; 14(9).
Yun HY, Chang MJ, Jung H, Chang V, Wang Q, Strydom N, Yoon YR, Savic RM. Prothionamide Dose Optimization Using Population Pharmacokinetics for Multidrug-Resistant Tuberculosis Patients. Antimicrob Agents Chemother. 2022 09 20; 66(9):e0189321.
Wilkins JJ, Svensson EM, Ernest JP, Savic RM, Simonsson USH, McIlleron H. Pharmacometrics in tuberculosis: progress and opportunities. Int J Antimicrob Agents. 2022 Sep; 60(3):106620.
Alffenaar JWC, Stocker SL, Forsman LD, Garcia-Prats A, Heysell SK, Aarnoutse RE, Akkerman OW, Aleksa A, van Altena R, de Oñata WA, Bhavani PK, Van't Boveneind-Vrubleuskaya N, Carvalho ACC, Centis R, Chakaya JM, Cirillo DM, Cho JG, D Ambrosio L, Dalcolmo MP, Denti P, Dheda K, Fox GJ, Hesseling AC, Kim HY, Köser CU, Marais BJ, Margineanu I, Märtson AG, Torrico MM, Nataprawira HM, Ong CWM, Otto-Knapp R, Peloquin CA, Silva DR, Ruslami R, Santoso P, Savic RM, Singla R, Svensson EM, Skrahina A, van Soolingen D, Srivastava S, Tadolini M, Tiberi S, Thomas TA, Udwadia ZF, Vu DH, Zhang W, Mpagama SG, Schön T, Migliori GB. Clinical standards for the dosing and management of TB drugs. Int J Tuberc Lung Dis. 2022 06 01; 26(6):483-499.
Imperial MZ, Nedelman JR, Conradie F, Savic RM. Proposed Linezolid Dosing Strategies to Minimize Adverse Events for Treatment of Extensively Drug-Resistant Tuberculosis. Clin Infect Dis. 2022 05 30; 74(10):1736-1747.
Lopez-Varela E, Abulfathi AA, Strydom N, Goussard P, van Wyk AC, Demers AM, Deventer AV, Garcia-Prats AJ, van der Merwe J, Zimmerman M, Carter CL, Janson J, Morrison J, Reuter H, Decloedt EH, Seddon JA, Svensson EM, Warren R, Savic RM, Dartois V, Hesseling AC. Drug concentration at the site of disease in children with pulmonary tuberculosis. J Antimicrob Chemother. 2022 05 29; 77(6):1710-1719.
Mathad JS, Savic R, Britto P, Jayachandran P, Wiesner L, Montepiedra G, Norman J, Zhang N, Townley E, Chakhtoura N, Bradford S, Patil S, Popson S, Chipato T, Rouzier V, Langat D, Chalermchockcharoentkit A, Kamthunzi P, Gupta A, Dooley KE. Pharmacokinetics and Safety of 3 Months of Weekly Rifapentine and Isoniazid for Tuberculosis Prevention in Pregnant Women. Clin Infect Dis. 2022 05 03; 74(9):1604-1613.
Radtke KK, Hesseling AC, Winckler JL, Draper HR, Solans BP, Thee S, Wiesner L, van der Laan LE, Fourie B, Nielsen J, Schaaf HS, Savic RM, Garcia-Prats AJ. Moxifloxacin Pharmacokinetics, Cardiac Safety, and Dosing for the Treatment of Rifampicin-Resistant Tuberculosis in Children. Clin Infect Dis. 2022 04 28; 74(8):1372-1381.
Green ML, Savic RM, Tonda M, Jorga K, Washington CB. Model-informed drug development of voxelotor in sickle cell disease: Exposure-response analysis to support dosing and confirm mechanism of action. CPT Pharmacometrics Syst Pharmacol. 2022 06; 11(6):698-710.
Savic RM, Green ML, Jorga K, Zager M, Washington CB. Model-informed drug development of voxelotor in sickle cell disease: Population pharmacokinetics in whole blood and plasma. CPT Pharmacometrics Syst Pharmacol. 2022 06; 11(6):687-697.
Radtke KK, Svensson EM, van der Laan LE, Hesseling AC, Savic RM, Garcia-Prats AJ. Emerging data on rifampicin pharmacokinetics and approaches to optimal dosing in children with tuberculosis. Expert Rev Clin Pharmacol. 2022 Feb; 15(2):161-174.
Kaya F, Ernest JP, LoMauro K, Gengenbacher M, Madani A, Aragaw WW, Zimmerman MD, Sarathy JP, Alvarez N, Daudelin I, Wang H, Lanni F, Weiner DM, Via LE, Barry CE, Olivier KN, Dick T, Podell BK, Savic RM, Dartois V. A Rabbit Model to Study Antibiotic Penetration at the Site of Infection for Nontuberculous Mycobacterial Lung Disease: Macrolide Case Study. Antimicrob Agents Chemother. 2022 03 15; 66(3):e0221221.
Yun HY, Chang V, Radtke KK, Wang Q, Strydom N, Chang MJ, Savic RM. Model-Based Efficacy and Toxicity Comparisons of Moxifloxacin for Multidrug-Resistant Tuberculosis. Open Forum Infect Dis. 2022 Mar; 9(3):ofab660.
Imperial MZ, Phillips PPJ, Nahid P, Savic RM. Precision-Enhancing Risk Stratification Tools for Selecting Optimal Treatment Durations in Tuberculosis Clinical Trials. Am J Respir Crit Care Med. 2021 11 01; 204(9):1086-1096.
Garcia-Cremades M, Solans BP, Strydom N, Vrijens B, Pillai GC, Shaffer C, Thomas B, Savic RM. Emerging Therapeutics, Technologies, and Drug Development Strategies to Address Patient Nonadherence and Improve Tuberculosis Treatment. Annu Rev Pharmacol Toxicol. 2022 01 06; 62:197-210.
Hills NK, Lyimo J, Nahid P, Savic RM, Lienhardt C, Phillips PPJ. A systematic review of endpoint definitions in late phase pulmonary tuberculosis therapeutic trials. Trials. 2021 Aug 03; 22(1):515.
Huddart S, Savic RM, Cattamanchi A. Is Glycemic Control the Secret to Tuberculosis Control? Am J Respir Crit Care Med. 2021 08 01; 204(3):254-255.
Zhang N, Savic RM, Boeree MJ, Peloquin CA, Weiner M, Heinrich N, Bliven-Sizemore E, Phillips PPJ, Hoelscher M, Whitworth W, Morlock G, Posey J, Stout JE, Mac Kenzie W, Aarnoutse R, Dooley KE, Tuberculosis Trials Consortium (TBTC) and Pan African Consortium for the Evaluation of Antituberculo. Optimising pyrazinamide for the treatment of tuberculosis. Eur Respir J. 2021 07; 58(1).
Ernest JP, Sarathy J, Wang N, Kaya F, Zimmerman MD, Strydom N, Wang H, Xie M, Gengenbacher M, Via LE, Barry CE, Carter CL, Savic RM, Dartois V. Lesion Penetration and Activity Limit the Utility of Second-Line Injectable Agents in Pulmonary Tuberculosis. Antimicrob Agents Chemother. 2021 09 17; 65(10):e0050621.
Gewitz AD, Solans BP, Mac Kenzie WR, Heilig C, Whitworth WC, Johnson JL, Nsubuga P, Dorman S, Weiner M, Savic RM, Tuberculosis Trials Consortium of the Centers for Disease Control and Prevention. Longitudinal Model-Based Biomarker Analysis of Exposure-Response Relationships in Adults with Pulmonary Tuberculosis. Antimicrob Agents Chemother. 2021 09 17; 65(10):e0179420.
Bigelow KM, Deitchman AN, Li SY, Barnes-Boyle K, Tyagi S, Soni H, Dooley KE, Savic RM, Nuermberger EL. Pharmacodynamic Correlates of Linezolid Activity and Toxicity in Murine Models of Tuberculosis. J Infect Dis. 2021 06 04; 223(11):1855-1864.
Walter ND, Born SEM, Robertson GT, Reichlen M, Dide-Agossou C, Ektnitphong VA, Rossmassler K, Ramey ME, Bauman AA, Ozols V, Bearrows SC, Schoolnik G, Dolganov G, Garcia B, Musisi E, Worodria W, Huang L, Davis JL, Nguyen NV, Nguyen HV, Nguyen ATV, Phan H, Wilusz C, Podell BK, Sanoussi ND, de Jong BC, Merle CS, Affolabi D, McIlleron H, Garcia-Cremades M, Maidji E, Eshun-Wilson F, Aguilar-Rodriguez B, Karthikeyan D, Mdluli K, Bansbach C, Lenaerts AJ, Savic RM, Nahid P, Vásquez JJ, Voskuil MI. Mycobacterium tuberculosis precursor rRNA as a measure of treatment-shortening activity of drugs and regimens. Nat Commun. 2021 05 18; 12(1):2899.
Dorman SE, Nahid P, Kurbatova EV, Phillips PPJ, Bryant K, Dooley KE, Engle M, Goldberg SV, Phan HTT, Hakim J, Johnson JL, Lourens M, Martinson NA, Muzanyi G, Narunsky K, Nerette S, Nguyen NV, Pham TH, Pierre S, Purfield AE, Samaneka W, Savic RM, Sanne I, Scott NA, Shenje J, Sizemore E, Vernon A, Waja Z, Weiner M, Swindells S, Chaisson RE, AIDS Clinical Trials Group, Tuberculosis Trials Consortium. Four-Month Rifapentine Regimens with or without Moxifloxacin for Tuberculosis. N Engl J Med. 2021 05 06; 384(18):1705-1718.
Hughes E, Wallender E, Mohamed Ali A, Jagannathan P, Savic RM. Malaria PK/PD and the Role Pharmacometrics Can Play in the Global Health Arena: Malaria Treatment Regimens for Vulnerable Populations. Clin Pharmacol Ther. 2021 10; 110(4):926-940.
Vora B, Brackman DJ, Zou L, Garcia-Cremades M, Sirota M, Savic RM, Giacomini KM. Oxypurinol pharmacokinetics and pharmacodynamics in healthy volunteers: Influence of BCRP Q141K polymorphism and patient characteristics. Clin Transl Sci. 2021 07; 14(4):1431-1443.
Jayachandran P, Knox SJ, Garcia-Cremades M, Savic RM. Clinical Pharmacokinetics of Oral Sodium Selenite and Dosing Implications in the Treatment of Patients with Metastatic Cancer. Drugs R D. 2021 Jun; 21(2):169-178.
Garcia-Prats AJ, Salazar-Austin N, Conway JH, Radtke K, LaCourse SM, Maleche-Obimbo E, Hesseling AC, Savic RM, Nachman S. Coronavirus Disease 2019 (COVID-19) Pharmacologic Treatments for Children: Research Priorities and Approach to Pediatric Studies. Clin Infect Dis. 2021 03 15; 72(6):1067-1073.
Ordonez AA, Tucker EW, Anderson CJ, Carter CL, Ganatra S, Kaushal D, Kramnik I, Lin PL, Madigan CA, Mendez S, Rao J, Savic RM, Tobin DM, Walzl G, Wilkinson RJ, Lacourciere KA, Via LE, Jain SK. Visualizing the dynamics of tuberculosis pathology using molecular imaging. J Clin Invest. 2021 03 01; 131(5).
Weiner M, Gelfond J, Johnson-Pais TL, Engle M, Johnson JL, Whitworth WC, Bliven-Sizemore E, Nsubuga P, Dorman SE, Savic R, Pharmacokinetics/Pharmacodynamics Group of Tuberculosis Trials Consortium. Decreased plasma rifapentine concentrations associated with AADAC single nucleotide polymorphism in adults with tuberculosis. J Antimicrob Chemother. 2021 02 11; 76(3):582-586.
Jayachandran P, Garcia-Cremades M, Vucicevic K, Bumpus NN, Anton P, Hendrix C, Savic R. A Mechanistic In Vivo/Ex Vivo Pharmacokinetic-Pharmacodynamic Model of Tenofovir for HIV Prevention. CPT Pharmacometrics Syst Pharmacol. 2021 03; 10(3):179-187.
Kang WH, Lee JY, Chae JW, Lee KR, Baek IH, Kim MS, Back HM, Jung S, Shaffer C, Savic R, Yun HY. Population Pharmacokinetic Method to Predict Within-Subject Variability Using Single-Period Clinical Data. Pharmaceuticals (Basel). 2021 Feb 03; 14(2).
Radtke KK, Hibma JE, Hesseling AC, Savic RM. Pragmatic global dosing recommendations for the 3-month, once-weekly rifapentine and isoniazid preventive TB regimen in children. Eur Respir J. 2021 01; 57(1).
Hughes E, Imperial M, Wallender E, Kajubi R, Huang L, Jagannathan P, Zhang N, Kakuru A, Natureeba P, Mwima MW, Muhindo M, Mwebaza N, Clark TD, Opira B, Nakalembe M, Havlir D, Kamya M, Rosenthal PJ, Dorsey G, Aweeka F, Savic RM. Piperaquine Exposure Is Altered by Pregnancy, HIV, and Nutritional Status in Ugandan Women. Antimicrob Agents Chemother. 2020 11 17; 64(12).
Hibma JE, Radtke KK, Dorman SE, Jindani A, Dooley KE, Weiner M, McIlleron HM, Savic RM. Rifapentine Population Pharmacokinetics and Dosing Recommendations for Latent Tuberculosis Infection. Am J Respir Crit Care Med. 2020 09 15; 202(6):866-877.
Nicol MR, Joshi A, Rizk ML, Sabato PE, Savic RM, Wesche D, Zheng JH, Cook J. Pharmacokinetics and Pharmacological Properties of Chloroquine and Hydroxychloroquine in the Context of COVID-19 Infection. Clin Pharmacol Ther. 2020 12; 108(6):1135-1149.
Fors J, Strydom N, Fox WS, Keizer RJ, Savic RM. Mathematical model and tool to explore shorter multi-drug therapy options for active pulmonary tuberculosis. PLoS Comput Biol. 2020 08; 16(8):e1008107.
Ernest JP, Strydom N, Wang Q, Zhang N, Nuermberger E, Dartois V, Savic RM. Development of New Tuberculosis Drugs: Translation to Regimen Composition for Drug-Sensitive and Multidrug-Resistant Tuberculosis. Annu Rev Pharmacol Toxicol. 2021 01 06; 61:495-516.
Garcia-Cremades M, Solans BP, Hughes E, Ernest JP, Wallender E, Savic RM. Response to "Quantitative Clinical Pharmacology INPUT to SARS-CoV-2 Therapeutics Should be Based on Robust Data". Clin Pharmacol Ther. 2020 08; 108(2):189.
Garcia-Cremades M, Solans BP, Hughes E, Ernest JP, Wallender E, Aweeka F, Luetkemeyer AF, Savic RM. Optimizing Hydroxychloroquine Dosing for Patients With COVID-19: An Integrative Modeling Approach for Effective Drug Repurposing. Clin Pharmacol Ther. 2020 08; 108(2):253-263.
Walsh KF, McAulay K, Lee MH, Vilbrun SC, Mathurin L, Jean Francois D, Zimmerman M, Kaya F, Zhang N, Saito K, Ocheretina O, Savic R, Dartois V, Johnson WD, Pape JW, Nathan C, Fitzgerald DW. Early Bactericidal Activity Trial of Nitazoxanide for Pulmonary Tuberculosis. Antimicrob Agents Chemother. 2020 04 21; 64(5).
Lee SA, Telwatte S, Hatano H, Kashuba ADM, Cottrell ML, Hoh R, Liegler TJ, Stephenson S, Somsouk M, Hunt PW, Deeks SG, Yukl S, Savic RM. Antiretroviral Therapy Concentrations Differ in Gut vs. Lymph Node Tissues and Are Associated With HIV Viral Transcription by a Novel RT-ddPCR Assay. J Acquir Immune Defic Syndr. 2020 04 15; 83(5):530-537.
Dooley KE, Savic R, Gupte A, Marzinke MA, Zhang N, Edward VA, Wolf L, Sebe M, Likoti M, Fyvie MJ, Shibambo I, Beattie T, Chaisson RE, Churchyard GJ, DOLPHIN Study Team. Once-weekly rifapentine and isoniazid for tuberculosis prevention in patients with HIV taking dolutegravir-based antiretroviral therapy: a phase 1/2 trial. Lancet HIV. 2020 06; 7(6):e401-e409.
Zhang N, Strydom N, Tyagi S, Soni H, Tasneen R, Nuermberger EL, Savic RM. Mechanistic Modeling of Mycobacterium tuberculosis Infection in Murine Models for Drug and Vaccine Efficacy Studies. Antimicrob Agents Chemother. 2020 02 21; 64(3).
Vernon A, Fielding K, Savic R, Dodd L, Nahid P. The importance of adherence in tuberculosis treatment clinical trials and its relevance in explanatory and pragmatic trials. PLoS Med. 2019 12; 16(12):e1002884.
Knox SJ, Jayachandran P, Keeling CA, Stevens KJ, Sandhu N, Stamps-DeAnda SL, Savic R, Shura L, Buyyounouski MK, Grimes K. Results from a Phase 1 Study of Sodium Selenite in Combination with Palliative Radiation Therapy in Patients with Metastatic Cancer. Transl Oncol. 2019 Nov; 12(11):1525-1531.
Radtke KK, Dooley KE, Dodd PJ, Garcia-Prats AJ, McKenna L, Hesseling AC, Savic RM. Alternative dosing guidelines to improve outcomes in childhood tuberculosis: a mathematical modelling study. Lancet Child Adolesc Health. 2019 09; 3(9):636-645.
Friedman N, Pancer Z, Savic R, Tseng F, Lee MS, Mclean L, Bagli DJ, Tessaro MO. Accuracy of point-of-care ultrasound by pediatric emergency physicians for testicular torsion. J Pediatr Urol. 2019 Dec; 15(6):608.e1-608.e6.
Dooley KE, Hanna D, Mave V, Eisenach K, Savic RM. Advancing the development of new tuberculosis treatment regimens: The essential role of translational and clinical pharmacology and microbiology. PLoS Med. 2019 07; 16(7):e1002842.
Garcia-Prats AJ, Schaaf HS, Draper HR, Garcia-Cremades M, Winckler J, Wiesner L, Hesseling AC, Savic RM. Pharmacokinetics, optimal dosing, and safety of linezolid in children with multidrug-resistant tuberculosis: Combined data from two prospective observational studies. PLoS Med. 2019 04; 16(4):e1002789.
Sarathy J, Blanc L, Alvarez-Cabrera N, O'Brien P, Dias-Freedman I, Mina M, Zimmerman M, Kaya F, Ho Liang HP, Prideaux B, Dietzold J, Salgame P, Savic RM, Linderman J, Kirschner D, Pienaar E, Dartois V. Fluoroquinolone Efficacy against Tuberculosis Is Driven by Penetration into Lesions and Activity against Resident Bacterial Populations. Antimicrob Agents Chemother. 2019 05; 63(5).
Strydom N, Gupta SV, Fox WS, Via LE, Bang H, Lee M, Eum S, Shim T, Barry CE, Zimmerman M, Dartois V, Savic RM. Tuberculosis drugs' distribution and emergence of resistance in patient's lung lesions: A mechanistic model and tool for regimen and dose optimization. PLoS Med. 2019 04; 16(4):e1002773.
Wallender E, Zhang N, Conrad M, Kakuru A, Muhindo M, Tumwebaze P, Kajubi R, Mota D, Legac J, Jagannathan P, Havlir D, Kamya M, Dorsey G, Aweeka F, Rosenthal PJ, Savic RM. Modeling Prevention of Malaria and Selection of Drug Resistance with Different Dosing Schedules of Dihydroartemisinin-Piperaquine Preventive Therapy during Pregnancy in Uganda. Antimicrob Agents Chemother. 2019 02; 63(2).
Imperial MZ, Nahid P, Phillips PPJ, Davies GR, Fielding K, Hanna D, Hermann D, Wallis RS, Johnson JL, Lienhardt C, Savic RM. Publisher Correction: A patient-level pooled analysis of treatment-shortening regimens for drug-susceptible pulmonary tuberculosis. Nat Med. 2019 Jan; 25(1):190.
Blanc L, Daudelin IB, Podell BK, Chen PY, Zimmerman M, Martinot AJ, Savic RM, Prideaux B, Dartois V. High-resolution mapping of fluoroquinolones in TB rabbit lesions reveals specific distribution in immune cell types. Elife. 2018 11 14; 7.
Imperial MZ, Nahid P, Phillips PPJ, Davies GR, Fielding K, Hanna D, Hermann D, Wallis RS, Johnson JL, Lienhardt C, Savic RM. A patient-level pooled analysis of treatment-shortening regimens for drug-susceptible pulmonary tuberculosis. Nat Med. 2018 11; 24(11):1708-1715.
Lee SA, Elliott JH, McMahon J, Hartogenesis W, Bumpus NN, Lifson JD, Gorelick RJ, Bacchetti P, Deeks SG, Lewin SR, Savic RM. Population Pharmacokinetics and Pharmacodynamics of Disulfiram on Inducing Latent HIV-1 Transcription in a Phase IIb Trial. Clin Pharmacol Ther. 2019 03; 105(3):692-702.
Savic RM, Jagannathan P, Kajubi R, Huang L, Zhang N, Were M, Kakuru A, Muhindo MK, Mwebaza N, Wallender E, Clark TD, Opira B, Kamya M, Havlir DV, Rosenthal PJ, Dorsey G, Aweeka FT. Intermittent Preventive Treatment for Malaria in Pregnancy: Optimization of Target Concentrations of Dihydroartemisinin-Piperaquine. Clin Infect Dis. 2018 09 14; 67(7):1079-1088.
Blanc L, Sarathy JP, Alvarez Cabrera N, O'Brien P, Dias-Freedman I, Mina M, Sacchettini J, Savic RM, Gengenbacher M, Podell BK, Prideaux B, Ioerger T, Dick T, Dartois V. Impact of immunopathology on the antituberculous activity of pyrazinamide. J Exp Med. 2018 08 06; 215(8):1975-1986.
Rifat D, Prideaux B, Savic RM, Urbanowski ME, Parsons TL, Luna B, Marzinke MA, Ordonez AA, DeMarco VP, Jain SK, Dartois V, Bishai WR, Dooley KE. Pharmacokinetics of rifapentine and rifampin in a rabbit model of tuberculosis and correlation with clinical trial data. Sci Transl Med. 2018 04 04; 10(435).
Wallender E, Vucicevic K, Jagannathan P, Huang L, Natureeba P, Kakuru A, Muhindo M, Nakalembe M, Havlir D, Kamya M, Aweeka F, Dorsey G, Rosenthal PJ, Savic RM. Predicting Optimal Dihydroartemisinin-Piperaquine Regimens to Prevent Malaria During Pregnancy for Human Immunodeficiency Virus-Infected Women Receiving Efavirenz. J Infect Dis. 2018 03 05; 217(6):964-972.
Guiastrennec B, Ramachandran G, Karlsson MO, Kumar AKH, Bhavani PK, Gangadevi NP, Swaminathan S, Gupta A, Dooley KE, Savic RM. Suboptimal Antituberculosis Drug Concentrations and Outcomes in Small and HIV-Coinfected Children in India: Recommendations for Dose Modifications. Clin Pharmacol Ther. 2018 10; 104(4):733-741.
Denti P, Garcia-Prats AJ, Draper HR, Wiesner L, Winckler J, Thee S, Dooley KE, Savic RM, McIlleron HM, Schaaf HS, Hesseling AC. Levofloxacin Population Pharmacokinetics in South African Children Treated for Multidrug-Resistant Tuberculosis. Antimicrob Agents Chemother. 2018 02; 62(2).
Savic RM, Novakovic AM, Ekblom M, Munafo A, Karlsson MO. Population Pharmacokinetics of Cladribine in Patients with Multiple Sclerosis. Clin Pharmacokinet. 2017 10; 56(10):1245-1253.
Bartelink IH, Prideaux B, Krings G, Wilmes L, Lee PRE, Bo P, Hann B, Coppé JP, Heditsian D, Swigart-Brown L, Jones EF, Magnitsky S, Keizer RJ, de Vries N, Rosing H, Pawlowska N, Thomas S, Dhawan M, Aggarwal R, Munster PN, Esserman LJ, Ruan W, Wu AHB, Yee D, Dartois V, Savic RM, Wolf DM, van 't Veer L. Heterogeneous drug penetrance of veliparib and carboplatin measured in triple negative breast tumors. Breast Cancer Res. 2017 Sep 11; 19(1):107.
Wilkinson RJ, Rohlwink U, Misra UK, van Crevel R, Mai NTH, Dooley KE, Caws M, Figaji A, Savic R, Solomons R, Thwaites GE, Tuberculous Meningitis International Research Consortium. Tuberculous meningitis. Nat Rev Neurol. 2017 Oct; 13(10):581-598.
Bartelink IH, Zhang N, Keizer RJ, Strydom N, Converse PJ, Dooley KE, Nuermberger EL, Savic RM. New Paradigm for Translational Modeling to Predict Long-term Tuberculosis Treatment Response. Clin Transl Sci. 2017 Sep; 10(5):366-379.
Alsultan A, Savic R, Dooley KE, Weiner M, Whitworth W, Mac Kenzie WR, Peloquin CA, Tuberculosis Trials Consortium. Population Pharmacokinetics of Pyrazinamide in Patients with Tuberculosis. Antimicrob Agents Chemother. 2017 06; 61(6).
Savic RM, Weiner M, MacKenzie WR, Engle M, Whitworth WC, Johnson JL, Nsubuga P, Nahid P, Nguyen NV, Peloquin CA, Dooley KE, Dorman SE, Tuberculosis Trials Consortium of the Centers for Disease Control and Prevention. Defining the optimal dose of rifapentine for pulmonary tuberculosis: Exposure-response relations from two phase II clinical trials. Clin Pharmacol Ther. 2017 Aug; 102(2):321-331.
Nguyen TH, Mouksassi MS, Holford N, Al-Huniti N, Freedman I, Hooker AC, John J, Karlsson MO, Mould DR, Pérez Ruixo JJ, Plan EL, Savic R, van Hasselt JG, Weber B, Zhou C, Comets E, Mentré F, Model Evaluation Group of the International Society of Pharmacometrics (ISoP) Best Practice Committe. Model Evaluation of Continuous Data Pharmacometric Models: Metrics and Graphics. CPT Pharmacometrics Syst Pharmacol. 2017 02; 6(2):87-109.
Rizk ML, Zou L, Savic RM, Dooley KE. Importance of Drug Pharmacokinetics at the Site of Action. Clin Transl Sci. 2017 05; 10(3):133-142.
Bartelink IH, Lalmohamed A, van Reij EM, Dvorak CC, Savic RM, Zwaveling J, Bredius RG, Egberts AC, Bierings M, Kletzel M, Shaw PJ, Nath CE, Hempel G, Ansari M, Krajinovic M, Théorêt Y, Duval M, Keizer RJ, Bittencourt H, Hassan M, Güngör T, Wynn RF, Veys P, Cuvelier GD, Marktel S, Chiesa R, Cowan MJ, Slatter MA, Stricherz MK, Jennissen C, Long-Boyle JR, Boelens JJ. Association of busulfan exposure with survival and toxicity after haemopoietic cell transplantation in children and young adults: a multicentre, retrospective cohort analysis. Lancet Haematol. 2016 Nov; 3(11):e526-e536.
Jayakumar A, Savic RM, Everett CK, Benator D, Alland D, Heilig CM, Weiner M, Friedrich SO, Martinson NA, Kerrigan A, Zamudio C, Goldberg SV, Whitworth WC, Davis JL, Nahid P. Xpert MTB/RIF Assay Shows Faster Clearance of Mycobacterium tuberculosis DNA with Higher Levels of Rifapentine Exposure. J Clin Microbiol. 2016 12; 54(12):3028-3033.
Goswami S, Yee SW, Xu F, Sridhar SB, Mosley JD, Takahashi A, Kubo M, Maeda S, Davis RL, Roden DM, Hedderson MM, Giacomini KM, Savic RM. A Longitudinal HbA1c Model Elucidates Genes Linked to Disease Progression on Metformin. Clin Pharmacol Ther. 2016 Nov; 100(5):537-547.
Hibma JE, Zur AA, Castro RA, Wittwer MB, Keizer RJ, Yee SW, Goswami S, Stocker SL, Zhang X, Huang Y, Brett CM, Savic RM, Giacomini KM. The Effect of Famotidine, a MATE1-Selective Inhibitor, on the Pharmacokinetics and Pharmacodynamics of Metformin. Clin Pharmacokinet. 2016 06; 55(6):711-21.
Conde MB, Mello FC, Duarte RS, Cavalcante SC, Rolla V, Dalcolmo M, Loredo C, Durovni B, Armstrong DT, Efron A, Barnes GL, Marzinke MA, Savic RM, Dooley KE, Cohn S, Moulton LH, Chaisson RE, Dorman SE. A Phase 2 Randomized Trial of a Rifapentine plus Moxifloxacin-Based Regimen for Treatment of Pulmonary Tuberculosis. PLoS One. 2016; 11(5):e0154778.
Bahr NC, Marais S, Caws M, van Crevel R, Wilkinson RJ, Tyagi JS, Thwaites GE, Boulware DR, Tuberculous Meningitis International Research Consortium. GeneXpert MTB/Rif to Diagnose Tuberculous Meningitis: Perhaps the First Test but not the Last. Clin Infect Dis. 2016 May 01; 62(9):1133-5.
Larsen MS, Keizer R, Munro G, Mørk A, Holm R, Savic R, Kreilgaard M. Pharmacokinetic/Pharmacodynamic Relationship of Gabapentin in a CFA-induced Inflammatory Hyperalgesia Rat Model. Pharm Res. 2016 May; 33(5):1133-43.
Gupta A, Mathad JS, Abdel-Rahman SM, Albano JD, Botgros R, Brown V, Browning RS, Dawson L, Dooley KE, Gnanashanmugam D, Grinsztejn B, Hernandez-Diaz S, Jean-Philippe P, Kim P, Lyerly AD, Mirochnick M, Mofenson LM, Montepiedra G, Piper J, Sahin L, Savic R, Smith B, Spiegel H, Swaminathan S, Watts DH, White A. Toward Earlier Inclusion of Pregnant and Postpartum Women in Tuberculosis Drug Trials: Consensus Statements From an International Expert Panel. Clin Infect Dis. 2016 Mar 15; 62(6):761-769.
Elliott JH, McMahon JH, Chang CC, Lee SA, Hartogensis W, Bumpus N, Savic R, Roney J, Hoh R, Solomon A, Piatak M, Gorelick RJ, Lifson J, Bacchetti P, Deeks SG, Lewin SR. Short-term administration of disulfiram for reversal of latent HIV infection: a phase 2 dose-escalation study. Lancet HIV. 2015 Dec; 2(12):e520-9.
Savic RM, Ruslami R, Hibma JE, Hesseling A, Ramachandran G, Ganiem AR, Swaminathan S, McIlleron H, Gupta A, Thakur K, van Crevel R, Aarnoutse R, Dooley KE. Pediatric tuberculous meningitis: Model-based approach to determining optimal doses of the anti-tuberculosis drugs rifampin and levofloxacin for children. Clin Pharmacol Ther. 2015 Dec; 98(6):622-9.
Sundell K, Jagannathan P, Huang L, Bigira V, Kapisi J, Kakuru MM, Savic R, Kamya MR, Dorsey G, Aweeka F. Variable piperaquine exposure significantly impacts protective efficacy of monthly dihydroartemisinin-piperaquine for the prevention of malaria in Ugandan children. Malar J. 2015 Sep 24; 14:368.
Via LE, Savic R, Weiner DM, Zimmerman MD, Prideaux B, Irwin SM, Lyon E, O'Brien P, Gopal P, Eum S, Lee M, Lanoix JP, Dutta NK, Shim T, Cho JS, Kim W, Karakousis PC, Lenaerts A, Nuermberger E, Barry CE, Dartois V. Host-Mediated Bioactivation of Pyrazinamide: Implications for Efficacy, Resistance, and Therapeutic Alternatives. ACS Infect Dis. 2015 May 08; 1(5):203-214.
Long-Boyle JR, Savic R, Yan S, Bartelink I, Musick L, French D, Law J, Horn B, Cowan MJ, Dvorak CC. Population pharmacokinetics of busulfan in pediatric and young adult patients undergoing hematopoietic cell transplant: a model-based dosing algorithm for personalized therapy and implementation into routine clinical use. Ther Drug Monit. 2015 Apr; 37(2):236-45.
Dooley KE, Savic RM, Park JG, Cramer Y, Hafner R, Hogg E, Janik J, Marzinke MA, Patterson K, Benson CA, Hovind L, Dorman SE, Haas DW, ACTG A5311 Study Team. Novel dosing strategies increase exposures of the potent antituberculosis drug rifapentine but are poorly tolerated in healthy volunteers. Antimicrob Agents Chemother. 2015; 59(6):3399-405.
Bartelink IH, Savic RM, Dorsey G, Ruel T, Gingrich D, Scherpbier HJ, Capparelli E, Jullien V, Young SL, Achan J, Plenty A, Charlebois E, Kamya M, Havlir D, Aweeka F. The effect of malnutrition on the pharmacokinetics and virologic outcomes of lopinavir, efavirenz and nevirapine in food insecure HIV-infected children in Tororo, Uganda. Pediatr Infect Dis J. 2015 Mar; 34(3):e63-70.
Dorman SE, Savic RM, Goldberg S, Stout JE, Schluger N, Muzanyi G, Johnson JL, Nahid P, Hecker EJ, Heilig CM, Bozeman L, Feng PJ, Moro RN, MacKenzie W, Dooley KE, Nuermberger EL, Vernon A, Weiner M, Tuberculosis Trials Consortium. Daily rifapentine for treatment of pulmonary tuberculosis. A randomized, dose-ranging trial. Am J Respir Crit Care Med. 2015 Feb 01; 191(3):333-43.
Sheffield JS, Siegel D, Mirochnick M, Heine RP, Nguyen C, Bergman KL, Savic RM, Long J, Dooley KE, Nesin M. Designing drug trials: considerations for pregnant women. Clin Infect Dis. 2014 Dec 15; 59 Suppl 7:S437-44.
Vreeman RC, Nyandiko WM, Liechty EA, Busakhala N, Bartelink IH, Savic RM, Scanlon ML, Ayaya SO, Blaschke TF. Impact of adherence and anthropometric characteristics on nevirapine pharmacokinetics and exposure among HIV-infected Kenyan children. J Acquir Immune Defic Syndr. 2014 Nov 01; 67(3):277-86.
Dooley KE, Luetkemeyer AF, Park JG, Allen R, Cramer Y, Murray S, Sutherland D, Aweeka F, Koletar SL, Marzan F, Bao J, Savic R, Haas DW, AIDS Clinical Trials Group A5306 Study Team. Phase I safety, pharmacokinetics, and pharmacogenetics study of the antituberculosis drug PA-824 with concomitant lopinavir-ritonavir, efavirenz, or rifampin. Antimicrob Agents Chemother. 2014 Sep; 58(9):5245-52.
Goswami S, Yee SW, Stocker S, Mosley JD, Kubo M, Castro R, Mefford JA, Wen C, Liang X, Witte J, Brett C, Maeda S, Simpson MD, Hedderson MM, Davis RL, Roden DM, Giacomini KM, Savic RM. Genetic variants in transcription factors are associated with the pharmacokinetics and pharmacodynamics of metformin. Clin Pharmacol Ther. 2014 Sep; 96(3):370-9.
Savic RM, Lu Y, Bliven-Sizemore E, Weiner M, Nuermberger E, Burman W, Dorman SE, Dooley KE. Population pharmacokinetics of rifapentine and desacetyl rifapentine in healthy volunteers: nonlinearities in clearance and bioavailability. Antimicrob Agents Chemother. 2014 Jun; 58(6):3035-42.
Weiner M, Savic RM, Kenzie WR, Wing D, Peloquin CA, Engle M, Bliven E, Prihoda TJ, Gelfond JA, Scott NA, Abdel-Rahman SM, Kearns GL, Burman WJ, Sterling TR, Villarino ME, Tuberculosis Trials Consortium PREVENT TB Pharmacokinetic Group. Rifapentine Pharmacokinetics and Tolerability in Children and Adults Treated Once Weekly With Rifapentine and Isoniazid for Latent Tuberculosis Infection. J Pediatric Infect Dis Soc. 2014 Jun; 3(2):132-45.
Bartelink IH, Savic RM, Mwesigwa J, Achan J, Clark T, Plenty A, Charlebois E, Kamya M, Young SL, Gandhi M, Havlir D, Cohan D, Aweeka F. Pharmacokinetics of lopinavir/ritonavir and efavirenz in food insecure HIV-infected pregnant and breastfeeding women in Tororo, Uganda. J Clin Pharmacol. 2014 Feb; 54(2):121-32.
Savic RM, Cowan MJ, Dvorak CC, Pai SY, Pereira L, Bartelink IH, Boelens JJ, Bredius RG, Wynn RF, Cuvelier GD, Shaw PJ, Slatter MA, Long-Boyle J. Effect of weight and maturation on busulfan clearance in infants and small children undergoing hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2013 Nov; 19(11):1608-14.
Yee SW, Nguyen AN, Brown C, Savic RM, Zhang Y, Castro RA, Cropp CD, Choi JH, Singh D, Tahara H, Stocker SL, Huang Y, Brett CM, Giacomini KM. Reduced renal clearance of cefotaxime in asians with a low-frequency polymorphism of OAT3 (SLC22A8). J Pharm Sci. 2013 Sep; 102(9):3451-7.
Savic RM, Barrail-Tran A, Duval X, Nembot G, Panhard X, Descamps D, Verstuyft C, Vrijens B, Taburet AM, Goujard C, Mentré F, ANRS 134–COPHAR 3 Study Group. Effect of adherence as measured by MEMS, ritonavir boosting, and CYP3A5 genotype on atazanavir pharmacokinetics in treatment-naive HIV-infected patients. Clin Pharmacol Ther. 2012 Nov; 92(5):575-83.
Stocker SL, McLachlan AJ, Savic RM, Kirkpatrick CM, Graham GG, Williams KM, Day RO. The pharmacokinetics of oxypurinol in people with gout. Br J Clin Pharmacol. 2012 Sep; 74(3):477-89.
Crawford KW, Ripin DH, Levin AD, Campbell JR, Flexner C, participants of Conference on Antiretroviral Drug Optimization. Optimising the manufacture, formulation, and dose of antiretroviral drugs for more cost-efficient delivery in resource-limited settings: a consensus statement. Lancet Infect Dis. 2012 Jul; 12(7):550-60.
Delattre M, Savic RM, Miller R, Karlsson MO, Lavielle M. Analysis of exposure-response of CI-945 in patients with epilepsy: application of novel mixed hidden Markov modeling methodology. J Pharmacokinet Pharmacodyn. 2012 Jun; 39(3):263-71.
Kang D, Bae KS, Houk BE, Savic RM, Karlsson MO. Standard Error of Empirical Bayes Estimate in NONMEM® VI. Korean J Physiol Pharmacol. 2012 Apr; 16(2):97-106.
Baverel PG, Savic RM, Karlsson MO. Two bootstrapping routines for obtaining imprecision estimates for nonparametric parameter distributions in nonlinear mixed effects models. J Pharmacokinet Pharmacodyn. 2011 Feb; 38(1):63-82.
Savic RM, Mentré F, Lavielle M. Implementation and evaluation of the SAEM algorithm for longitudinal ordered categorical data with an illustration in pharmacokinetics-pharmacodynamics. AAPS J. 2011 Mar; 13(1):44-53.
Savic RM, Karlsson MO. Evaluation of an extended grid method for estimation using nonparametric distributions. AAPS J. 2009 Sep; 11(3):615-27.
Savic R, Lavielle M. Performance in population models for count data, part II: a new SAEM algorithm. J Pharmacokinet Pharmacodyn. 2009 Aug; 36(4):367-79.
Savic RM, Karlsson MO. Importance of shrinkage in empirical bayes estimates for diagnostics: problems and solutions. AAPS J. 2009 Sep; 11(3):558-69.
Baverel PG, Savic RM, Wilkins JJ, Karlsson MO. Evaluation of the nonparametric estimation method in NONMEM VI: application to real data. J Pharmacokinet Pharmacodyn. 2009 Aug; 36(4):297-315.
Petersson KJ, Hanze E, Savic RM, Karlsson MO. Semiparametric distributions with estimated shape parameters. Pharm Res. 2009 Sep; 26(9):2174-85.
Carlsson KC, Savic RM, Hooker AC, Karlsson MO. Modeling subpopulations with the $MIXTURE subroutine in NONMEM: finding the individual probability of belonging to a subpopulation for the use in model analysis and improved decision making. AAPS J. 2009 Mar; 11(1):148-54.
Savic RM, Kjellsson MC, Karlsson MO. Evaluation of the nonparametric estimation method in NONMEM VI. Eur J Pharm Sci. 2009 Apr 11; 37(1):27-35.
Wilkins JJ, Savic RM, Karlsson MO, Langdon G, McIlleron H, Pillai G, Smith PJ, Simonsson US. Population pharmacokinetics of rifampin in pulmonary tuberculosis patients, including a semimechanistic model to describe variable absorption. Antimicrob Agents Chemother. 2008 Jun; 52(6):2138-48.
Savic RM, Jonker DM, Kerbusch T, Karlsson MO. Implementation of a transit compartment model for describing drug absorption in pharmacokinetic studies. J Pharmacokinet Pharmacodyn. 2007 Oct; 34(5):711-26.
Karlsson MO, Savic RM. Diagnosing model diagnostics. Clin Pharmacol Ther. 2007 Jul; 82(1):17-20.
Hong EU, Savic RM and Yim DS. Population Pharmacokinetic Analysis of the Oral Absorption Process of Tacrolimus in Healthy Volunteers . Kor J Clin Pharmacol Ther. 2007; 15(2):117-126.
Osterberg O, Savic RM, Karlsson MO, Simonsson US, Nørgaard JP, Walle JV, Agersø H. Pharmacokinetics of desmopressin administrated as an oral lyophilisate dosage form in children with primary nocturnal enuresis and healthy adults. J Clin Pharmacol. 2006 Oct; 46(10):1204-11.
Lindemalm S, Savic RM, Karlsson MO, Juliusson G, Liliemark J, Albertioni F. Application of population pharmacokinetics to cladribine. BMC Pharmacol. 2005 Mar 09; 5:4.