Davide Verotta, PhD

Professor

Department of Clinical Pharmacy

Elisabeth Fall

[email protected]

Phone: +1 415 476-1556

Fax: +1 415 476-1556

Location Required, Rm 001

UCSF Box 0622

Varies, CA 00000

United States

Links

Division of Clinical Pharmacology & Experimental Therapeutics

UCSF Profiles

Joint appointments

Professor in Residence, Department of Epidemiology and Biostatistics, School of Medicine

Educational programs

Pharmaceutical Sciences and Pharmacogenomics Graduate Program (PSPG)

What I do

I am a mathematical modeler and statistician with research interests in pharmacokinetics and pharmacodynamics and mathematical/statistical methods development.

Departmental research area

drug development and regulatory sciences

My research expertise

Bayesian modeling, PK/PD data and systems, population data analysis

Degrees

PhD, Biostatistics, University of California, Berkeley, 1992

PhD, Agricultural Sciences, University of Milan, 1982

Biography

Dr. Davide Verotta’s main research interests are in pharmacokinetics and pharmacodynamics (PKPD) and mathematical statistical (MS) modeling. In PKPD, his main areas of interest are: mechanistic modeling (where prior knowledge about parts of a PKPD system is embedded in the model describing it); the development of empirical models (where no prior knowledge is embedded in the model) to analyze, simulate and control; population PKPD modeling with particular regard to empirical methods for population data analysis. In MS modeling, his main interests are in linear and non-linear system analysis, control, and experimental design. He is involved in collaborative research with scientists and different investigators in PKPD and clinical therapy (notably HIV therapy) modeling. Additional areas of investigation are the use of Bayesian methods, in particular applied to pharmacogenomics and mechanistic modeling, fractional differential equations, and applications of functional data analysis to population PKPD.

Research keywords

Biofilms, Hypothermia, Induced, Pseudomonas aeruginosa, pharmacokinetics, Models, Statistical, Biological Models, Mathematical Computing, Biological Availability, drug evaluation, pharmacology, Nicotine, Hypoxia-Ischemia, Brain, Cytochrome P-450 CYP3A Inhibitors, Gentamicins, Nonlinear Dynamics

1.	Dean's Recognition for Excellence in Teaching, School of Pharmacy, UCSF, 2005

Publications

Schwartz JB, Gallagher JC, Jorde R, Berg V, Walsh J, Eastell R, Evans AL, Bowles S, Naylor KE, Jones KS, Schoenmakers I, Holick M, Orwoll E, Nielson C, Kaufmann M, Jones G, Bouillon R, Lai J, Verotta D, Bikle D. Determination of Free 25(OH)D Concentrations and Their Relationships to Total 25(OH)D in Multiple Clinical Populations. J Clin Endocrinol Metab. 2018 09 01; 103(9):3278-3288.

Huang L, Haagensen JAJ, Verotta D, Cheah V, Spormann AM, Aweeka F, Yang K. Determination of Tobramycin in M9 Medium by LC-MS/MS: Signal Enhancement by Trichloroacetic Acid. J Anal Methods Chem. 2018; 2018:7965124.

Verotta D, Haagensen J, Spormann AM, Yang K. Mathematical Modeling of Biofilm Structures Using COMSTAT Data. Comput Math Methods Med. 2017; 2017:7246286.

Haagensen J, Verotta D, Huang L, Engel J, Spormann AM, Yang K. Spatiotemporal pharmacodynamics of meropenem- and tobramycin-treated Pseudomonas aeruginosa biofilms. J Antimicrob Chemother. 2017 Dec 01; 72(12):3357-3365.

Haagensen JA, Verotta D, Huang L, Spormann A, Yang K. New in vitro model to study the effect of human simulated antibiotic concentrations on bacterial biofilms. Antimicrob Agents Chemother. 2015 Jul; 59(7):4074-81.

Huang L, Haagensen J, Verotta D, Lizak P, Aweeka F, Yang K. Determination of meropenem in bacterial media by LC-MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci. 2014 Jun 15; 961:71-6.

Frymoyer A, Lee S, Bonifacio SL, Meng L, Lucas SS, Guglielmo BJ, Sun Y, Verotta D. Every 36-h gentamicin dosing in neonates with hypoxic-ischemic encephalopathy receiving hypothermia. J Perinatol. 2013 Oct; 33(10):778-82.

Frymoyer A, Meng L, Bonifacio SL, Verotta D, Guglielmo BJ. Gentamicin pharmacokinetics and dosing in neonates with hypoxic ischemic encephalopathy receiving hypothermia. Pharmacotherapy. 2013 Jul; 33(7):718-26.

Frymoyer A, Verotta D, Jacobson P, Long-Boyle J. Population pharmacokinetics of unbound mycophenolic acid in adult allogeneic haematopoietic cell transplantation: effect of pharmacogenetic factors. Br J Clin Pharmacol. 2013 Feb; 75(2):463-75.

Dong BJ, Zheng Y, Hughes MD, Frymoyer A, Verotta D, Lizak P, Sawe F, Currier JS, Lockman S, Aweeka FT. Nevirapine pharmacokinetics and risk of rash and hepatitis among HIV-infected sub-Saharan African women. AIDS. 2012 Apr 24; 26(7):833-41.

Li L, Galloway GP, Verotta D, Everhart ET, Baggott MJ, Coyle JR, Lopez JC, Mendelson J. A method to quantify illicit intake of drugs from urine: methamphetamine. J Pharmacol Exp Ther. 2011 Jul; 338(1):31-6.

Verotta D. Fractional dynamics pharmacokinetics-pharmacodynamic models. J Pharmacokinet Pharmacodyn. 2010 Jun; 37(3):257-76.

Verotta D. Fractional compartmental models and multi-term Mittag-Leffler response functions. J Pharmacokinet Pharmacodyn. 2010 Apr; 37(2):209-15; discussion 217-20.

Schwartz JB, Verotta D. Population analyses of atorvastatin clearance in patients living in the community and in nursing homes. Clin Pharmacol Ther. 2009 Nov; 86(5):497-502.

Perger L, Rentsch KM, Kullak-Ublick GA, Verotta D, Fattinger K. Oral heroin in opioid-dependent patients: pharmacokinetic comparison of immediate and extended release tablets. Eur J Pharm Sci. 2009 Mar 02; 36(4-5):421-32.

Kshirsagar S, Gear R, Levine J, Verotta D. A mechanistic model for the sex-specific response to nalbuphine and naloxone in postoperative pain. J Pharmacokinet Pharmacodyn. 2008 Feb; 35(1):69-83.

Kang D, Verotta D. Reversible jump Markov chain Monte Carlo for deconvolution. J Pharmacokinet Pharmacodyn. 2007 Jun; 34(3):263-87.

Kshirsagar SA, Blaschke TF, Sheiner LB, Krygowski M, Acosta EP, Verotta D. Improving data reliability using a non-compliance detection method versus using pharmacokinetic criteria. J Pharmacokinet Pharmacodyn. 2007 Feb; 34(1):35-55.

Labbé L, Verotta D. A non-linear mixed effect dynamic model incorporating prior exposure and adherence to treatment to describe long-term therapy outcome in HIV-patients. J Pharmacokinet Pharmacodyn. 2006 Aug; 33(4):519-42.

Csajka C, Verotta D. Pharmacokinetic-pharmacodynamic modelling: history and perspectives. J Pharmacokinet Pharmacodyn. 2006 Jun; 33(3):227-79.

Kang D, Verotta D, Schwartz JB. Population analyses of amlodipine in patients living in the community and patients living in nursing homes. Clin Pharmacol Ther. 2006 Jan; 79(1):114-24.

Kang D, Schwartz JB, Verotta D. Sample size computations for PK/PD population models. J Pharmacokinet Pharmacodyn. 2005 Dec; 32(5-6):685-701.

Csajka C, Drover D, Verotta D. The use of a sum of inverse Gaussian functions to describe the absorption profile of drugs exhibiting complex absorption. Pharm Res. 2005 Aug; 22(8):1227-35.

Valle M, Di Salle E, Jannuzzo MG, Poggesi I, Rocchetti M, Spinelli R, Verotta D. A predictive model for exemestane pharmacokinetics/pharmacodynamics incorporating the effect of food and formulation. Br J Clin Pharmacol. 2005 Mar; 59(3):355-64.

Csajka C, Haller CA, Benowitz NL, Verotta D. Mechanistic pharmacokinetic modelling of ephedrine, norephedrine and caffeine in healthy subjects. Br J Clin Pharmacol. 2005 Mar; 59(3):335-45.

Csajka C, Imbimbo BP, Piccinno A, Dostert P, Verotta D. Mechanistic pharmacokinetic and pharmacodynamic modeling of CHF3381 (2-[(2,3-dihydro-1H-inden-2-yl)amino]acetamide monohydrochloride), a novel N-methyl-D-aspartate antagonist and monoamine oxidase-A inhibitor in healthy subjects. J Pharmacol Exp Ther. 2005 May; 313(2):647-57.

Kang D, Schwartz JB, Verotta D. A sample size computation method for non-linear mixed effects models with applications to pharmacokinetics models. Stat Med. 2004 Aug 30; 23(16):2551-66.

Valle M, Price RW, Nilsson A, Heyes M, Verotta D. CSF quinolinic acid levels are determined by local HIV infection: cross-sectional analysis and modelling of dynamics following antiretroviral therapy. Brain. 2004 May; 127(Pt 5):1047-60.

Verotta D. Volterra series in pharmacokinetics and pharmacodynamics. J Pharmacokinet Pharmacodyn. 2003 Oct; 30(5):337-62.

Kang D, Verotta D, Krecic-Shepard ME, Modi NB, Gupta SK, Schwartz JB. Population analyses of sustained-release verapamil in patients: effects of sex, race, and smoking. Clin Pharmacol Ther. 2003 Jan; 73(1):31-40.

Drover DR, Angst MS, Valle M, Ramaswamy B, Naidu S, Stanski DR, Verotta D. Input characteristics and bioavailability after administration of immediate and a new extended-release formulation of hydromorphone in healthy volunteers. Anesthesiology. 2002 Oct; 97(4):827-36.

Pitsiu M, Gries JM, Benowitz N, Gourlay SG, Verotta D. Modeling nicotine arterial-venous differences to predict arterial concentrations and input based on venous measurements: application to smokeless tobacco and nicotine gum. J Pharmacokinet Pharmacodyn. 2002 Aug; 29(4):383-402.

Verotta D, Schaedeli F. Non-linear dynamics models characterizing long-term virological data from AIDS clinical trials. Math Biosci. 2002 Apr; 176(2):163-83.

Schaedeli F, Pitsiu M, Benowitz NL, Gourlay SG, Verotta D. Influence of arterial vs. venous sampling site on nicotine tolerance model selection and parameter estimation. J Pharmacokinet Pharmacodyn. 2002 Feb; 29(1):49-66.

Lu J, Gries JM, Verotta D, Sheiner LB. Selecting reliable pharmacokinetic data for explanatory analyses of clinical trials in the presence of possible noncompliance. J Pharmacokinet Pharmacodyn. 2001 Aug; 28(4):343-62.

Pitsiu M, Sathyan G, Gupta S, Verotta D. A semiparametric deconvolution model to establish in vivo-in vitro correlation applied to OROS oxybutynin. J Pharm Sci. 2001 Jun; 90(6):702-12.

Gries JM, Verotta D. Linear mixed-effect multivariate adaptive regression splines applied to nonlinear pharmacokinetics data. J Biopharm Stat. 2000 Aug; 10(3):383-98.

Fattinger K, Benowitz NL, Jones RT, Verotta D. Nasal mucosal versus gastrointestinal absorption of nasally administered cocaine. Eur J Clin Pharmacol. 2000 Jul; 56(4):305-10.

Kindler CH, Verotta D, Gray AT, Gropper MA, Yost CS. Additive inhibition of nicotinic acetylcholine receptors by corticosteroids and the neuromuscular blocking drug vecuronium. Anesthesiology. 2000 Mar; 92(3):821-32.

Gries JM, Munafo A, Porchet HC, Verotta D. Down-regulation models and modeling of testosterone production induced by recombinant human choriogonadotropin. J Pharmacol Exp Ther. 1999 Apr; 289(1):371-7.

Verotta D. A general solution for nonparametric control of a linear system using computer-controlled infusion pumps. IEEE Trans Biomed Eng. 1999 Jan; 46(1):44-50.

Verotta D. Characterizing the variability of system kernel and input estimates. Ann Biomed Eng. 1998 Sep-Oct; 26(5):870-82.

Park K, Verotta D, Gupta SK, Sheiner LB. Use of a pharmacokinetic/pharmacodynamic model to design an optimal dose input profile. J Pharmacokinet Biopharm. 1998 Aug; 26(4):471-92.

Gries JM, Benowitz N, Verotta D. Importance of chronopharmacokinetics in design and evaluation of transdermal drug delivery systems. J Pharmacol Exp Ther. 1998 May; 285(2):457-63.

Park K, Verotta D, Gupta SK, Sheiner LB. Passive versus electrotransport-facilitated transdermal absorption of ketorolac. Clin Pharmacol Ther. 1998 Mar; 63(3):303-15.

Stanley G, Verotta D, Craft N, Siegel RA, Schwartz JB. Age effects on interrelationships between lung volume and heart rate during standing. Am J Physiol. 1997 11; 273(5):H2128-34.

Vanhove GF, Gries JM, Verotta D, Sheiner LB, Coombs R, Collier AC, Blaschke TF. Exposure-response relationships for saquinavir, zidovudine, and zalcitabine in combination therapy. Antimicrob Agents Chemother. 1997 Nov; 41(11):2433-8.

Vanhove GF, Kastrissios H, Gries JM, Verotta D, Park K, Collier AC, Squires K, Sheiner LB, Blaschke TF. Pharmacokinetics of saquinavir, zidovudine, and zalcitabine in combination therapy. Antimicrob Agents Chemother. 1997 Nov; 41(11):2428-32.

Park K, Verotta D, Blaschke TF, Sheiner LB. A semiparametric method for describing noisy population pharmacokinetic data. J Pharmacokinet Biopharm. 1997 Oct; 25(5):615-42.

Fattinger K, Verotta D, Benowitz NL. Pharmacodynamics of acute tolerance to multiple nicotinic effects in humans. J Pharmacol Exp Ther. 1997 Jun; 281(3):1238-46.

Verotta D. A general framework for non-parametric subject-specific and population deconvolution methods for in vivo-in vitro correlation. Adv Exp Med Biol. 1997; 423:43-52.

Gries JM, Troconiz IF, Verotta D, Jacobson M, Sheiner LB. A pooled analysis of CD4 response to zidovudine and zalcitabine treatment in patients with AIDS and AIDS-related complex. Clin Pharmacol Ther. 1997 Jan; 61(1):70-82.

Gries JM, Benowitz N, Verotta D. Chronopharmacokinetics of nicotine. Clin Pharmacol Ther. 1996 Oct; 60(4):385-95.

Fattinger KE, Verotta D, Porchet HC, Munafo A, Le Cotonnec JY, Sheiner LB. Modeling a bivariate control system: LH and testosterone response to the GnRH antagonist antide. Am J Physiol. 1996 Oct; 271(4 Pt 1):E775-87.

Stanley G, Verotta D, Craft N, Siegel RA, Schwartz JB. Age and autonomic effects on interrelationships between lung volume and heart rate. Am J Physiol. 1996 May; 270(5 Pt 2):H1833-40.

Gries JM, Upton R, Huang YF, Verotta D. A descriptive tool to characterize nonlinear kinetics, with applications to meperidine and lidocaine. J Pharm Sci. 1996 Apr; 85(4):362-8.

Verotta D. Concepts, properties, and applications of linear systems to describe distribution, identify input, and control endogenous substances and drugs in biological systems. Crit Rev Biomed Eng. 1996; 24(2-3):73-139.

Fattinger KE, Sheiner LB, Verotta D. A new method to explore the distribution of interindividual random effects in non-linear mixed effects models. Biometrics. 1995 Dec; 51(4):1236-51.

Fattinger KE, Verotta D. A nonparametric subject-specific population method for deconvolution: I. Description, internal validation, and real data examples. J Pharmacokinet Biopharm. 1995 Dec; 23(6):581-610.

Fattinger KE, Verotta D. A nonparametric subject-specific population method for deconvolution: II. External validation. J Pharmacokinet Biopharm. 1995 Dec; 23(6):611-34.

Fattinger KE, Verotta D. Estimating bioavailability when clearance changes in time: the effect of model misspecification. Clin Pharmacol Ther. 1995 Nov; 58(5):595-600.

Sheiner LB, Verotta D. Further notes on physiologic indirect response models. Clin Pharmacol Ther. 1995 Aug; 58(2):238-40.

Verotta D, Sheiner LB. A general conceptual model for non-steady state pharmacokinetic/pharmacodynamic data. J Pharmacokinet Biopharm. 1995 Feb; 23(1):1-4.

Gumbleton M, Oie S, Verotta D. Pharmacokinetic-pharmacodynamic (PK-PD) modelling in non-steady-state studies and arterio-venous drug concentration differences. Br J Clin Pharmacol. 1994 Nov; 38(5):389-400.

Troconiz IF, Sheiner LB, Verotta D. Semiparametric models for antagonistic drug interactions. J Appl Physiol (1985). 1994 May; 76(5):2224-33.

Verotta D. Estimation and model selection in constrained deconvolution. Ann Biomed Eng. 1993 Nov-Dec; 21(6):605-20.

Verotta D. Two constrained deconvolution methods using spline functions. J Pharmacokinet Biopharm. 1993 Oct; 21(5):609-36.

Schwartz JB, Troconiz IF, Verotta D, Liu S, Capili H. Aging effects on stereoselective pharmacokinetics and pharmacodynamics of verapamil. J Pharmacol Exp Ther. 1993 May; 265(2):690-8.

Mandema JW, Verotta D, Sheiner LB. Building population pharmacokinetic--pharmacodynamic models. I. Models for covariate effects. J Pharmacokinet Biopharm. 1992 Oct; 20(5):511-28.

Cahalan MK, Hashimoto Y, Aizawa K, Verotta D, Ionescu P, Balea M, Eger EI, Benet LZ, Ehrenfeld WK, Goldstone J. Elderly, conscious patients have an accentuated hypotensive response to nitroglycerin. Anesthesiology. 1992 Oct; 77(4):646-55.

Verotta D, Sheiner LB. Comparing responses when each response is a curve. Am J Physiol. 1992 Jul; 263(1 Pt 2):R206-14.

Verotta D, Kitts J, Rodriguez R, Coldwell J, Miller RD, Sheiner LB. Reversal of neuromuscular blockade in humans by neostigmine and edrophonium: a mathematical model. J Pharmacokinet Biopharm. 1991 Dec; 19(6):713-29.

Verotta D, Sheiner LB. Semiparametric analysis of non-steady-state pharmacodynamic data. J Pharmacokinet Biopharm. 1991 Dec; 19(6):691-712.

Verotta D, Sheiner LB, Beal SL. Mean time parameters for generalized physiological flow models (semihomogeneous linear systems). J Pharmacokinet Biopharm. 1991 Jun; 19(3):319-31.

Verotta D. An application of the D-optimal criterion to define the experimental design for a particular class of semi-parametric models. Comput Methods Programs Biomed. 1990 Nov; 33(3):181-7.

Verotta D. Comments on two recent deconvolution methods. J Pharmacokinet Biopharm. 1990 Oct; 18(5):483-9; discussion 489-99.

Björkman S, Stanski DR, Verotta D, Harashima H. Comparative tissue concentration profiles of fentanyl and alfentanil in humans predicted from tissue/blood partition data obtained in rats. Anesthesiology. 1990 May; 72(5):865-73.

Schwartz JB, Verotta D, Sheiner LB. Pharmacodynamic modeling of verapamil effects under steady-state and nonsteady-state conditions. J Pharmacol Exp Ther. 1989 Dec; 251(3):1032-8.

Boyd RA, Chin SK, Don-Pedro O, Verotta D, Sheiner LB, Williams RL, Giacomini KM. The pharmacokinetics and pharmacodynamics of diltiazem and its metabolites in healthy adults after a single oral dose. Clin Pharmacol Ther. 1989 Oct; 46(4):408-19.

Verotta D, Sheiner LB, Ebling WF, Stanski DR. A semiparametric approach to physiological flow models. J Pharmacokinet Biopharm. 1989 Aug; 17(4):463-91.

Verotta D, Beal SL, Sheiner LB. Semiparametric approach to pharmacokinetic-pharmacodynamic data. Am J Physiol. 1989 Apr; 256(4 Pt 2):R1005-10.

Imbimbo BP, Imbimbo E, Daniotti S, Verotta D, Bassotti G. A new criterion for selection of pharmacokinetic multiexponential equations. J Pharm Sci. 1988 Sep; 77(9):784-9.

Verotta D, Petrillo P, La Regina A, Rocchetti M, Tavani A. D-optimal design applied to binding saturation curves of an enkephalin analog in rat brain. Life Sci. 1988; 42(6):735-43.

Verotta D, Sheiner LB. Simultaneous modeling of pharmacokinetics and pharmacodynamics: an improved algorithm. Comput Appl Biosci. 1987 Nov; 3(4):345-9.

Schüttler J, Stanski DR, White PF, Trevor AJ, Horai Y, Verotta D, Sheiner LB. Pharmacodynamic modeling of the EEG effects of ketamine and its enantiomers in man. J Pharmacokinet Biopharm. 1987 Jun; 15(3):241-53.