Pharmacodynamic pharmacokinetic analysis

Mentre, F. Ebelin, M.E. Validation of population pharmacokinetic/pharmacodynamic analyses review of proposed approaches. In The Population Approach Measuring and Managing Variability in Response, Concentration and Dose Aarons, L., Balant, L.P., Danhof M., Gex-Fabry, M., Gundert-Remy, U.A., Karlsson, M.O., Mentre, F., Morselli, R.L., Rombut, F., Rowland, M., Steimer, J.-L., Voseh, S., Eds. Commission of the European Communities, European Cooperation in the Eield of Scientific and Technical Research Brussels, 1997 147-160. Ette, E.I. Williams, P. Sun, H. Fadiran, E. Ajayi, F.O. Onyiah, L.C. The process of knowledge discovery from large pharmacokinetic data sets. J. Clin. Pharmacol. 2001, 41 (1), 25-34. 

F. Mentre and M. E. Ebelen, Validation of population pharmacokinetic-pharmacodynamic analyses review of proposed approaches, in The Population Approach Measuring and Managing Variability in Response Concentration and Dose (COST Bl). Office for Official Publications of the European Communities, Brussels, 1997, pp. 146-160. 

S. C. Olson, H. Bockbrader, R. A. Boyd, et al.. Impact of popnlation pharmacokinetic-pharmacodynamic analyses on the drug development process experience at Parke-Davis. Clin Pharmacokinet 38 449-459 (2000). 

Table 7.2 Co variates that have been used in population pharmacokinetic-pharmacodynamic analyses.

Olson, S.C., Bockbrader, H., Boyd, R.A., Cook, J., Koup, J.R., Lalonde, R.L., Siedlik, P.H., and Powell, J.R. Impact of population pharmacokinetic-pharmacodynamic analyses on the drug development process. Clinical Pharmacokinetics 2000 38 449-459. 

Homestam, B., Jerling, M., Karlsson, M.O., and Held, P. DAAf Trial Group, Intravenously administered digoxin in patients with acute atrial fibrillation a population pharmacokinetic/pharmacodynamic analysis based on the digitalis in acute atrial fibrillation trial, Eur.. Clin. Pharmacol., 58, 747-755, 2003. 

Blin, O., Jacquet, A., Callamand, S., Jouve, E., Habib, M., Gayraud, D., Durand, A., Bruguerolle, B., and Pisano, P., Pharmacokinetic-pharmacodynamic analysis of mnesic effects of lorazepam in healthy volunteers, Br. J. Clin. Pharmacol., 48, 510-512, 1999. 

Wakelkamp, M., Alvan, G., and Paintaud, G., The time of maximum effect for model selection in pharmacokinetic-pharmacodynamic analysis applied to frusemide, Br.. Clin. Pharmacol., 45, 63-70, 1998. 

Tabrizi-Fard, M.A. and H.L. Fung. 1998. Effects of nitro-L-arginine on blood pressure and cardiac index in anesthetized rats a pharmacokinetic-pharmacodynamic analysis. Pharm. Res. 15 1063-1068. 

Blin O, Jacquet A, Callamand S, Jouve E, Habib M, Gayraud D, Durand A, Bruguerolle B, Pisano P. Pharmacokinetic-pharmacodynamic analysis of amnesic effects of lorazepam in healthy volunteers. Br J Clin Pharmacol 1999 48(4) 510-2. 

Cox EH, Veyrat-FoIIet C, Beal SL, Fuseau E, Kenkare S, Sheiner LB. A population pharmacokinetic-pharmacodynamic analysis of repeated measures time-to-event pharmacodynamic responses The antiemetic effect of ondansetron. J Pharmacokinet Biopharm 1999 27 625M4. 

Stepensky, D. Friedman, M. Raz, I. Hoffman, A. Pharmacokinetic-pharmacodynamic analysis of the glucose-lowering effect of metformin in diabetic rats reveals first-pass pharmacodynamic effect. Drug Metab. Dispos. 2002, 30 (8), 861-868. 

Obach RS. 1996a. Prediction of human pharmacokinetics using in vitro-in vivo correlations . In Pharmacokinetic/Pharmacodynamic Analysis ... 

U. Wahlby, A. H. Thomson, P. A. MiUigan, and M. O. Karlsson, Models for time-varying covariates in population pharmacokinetic-pharmacodynamic analysis. Br J Clin Pharmacol 58 367-377 (2004). 

T. N. Johnson, A. Rostami-Hodjegan, J. M. Goddard, M. S. Tanner, and G. T. Sucker, Contribution of midazolam and its 1-hydroxy metabolite to preoperative sedation in children a pharmacokinetic-pharmacodynamic analysis. Br J Anaesth 89(3) 428-437 (2002). 

A. Hsu, J. Isaacson, S. Brun, B. Bernstein, W. Lam, R. Bertz, C. Foit, K. Rynkiewicz, B. Richards, M. King, R. Rode, D. J. Kempf, G. R. Granneman, and E. Sun, Pharmacokinetic-pharmacodynamic analysis of lopinavir-ritonavir in combination with efavirenz and two nucleoside reverse transcriptase inhibitors in extensively pretreated hnman immunodeficiency virus-infected patients. Antimicrob Agents Chemother 47(l) 350-359 (2003). 

D. R. Mould, C. B. Davis, E. A. Minthorn, D. C. Kwok, M. J. Ehott, M. E. Luggen, and M. C. Totoritis, Population pharmacokinetic/pharmacodynamic analysis of the effects of Clenoliximab, a PR1MAT1ZED anti-CD4 monoclonal antibody, on T lymphocytes, following single doses to patients with active rheumatoid arthritis. Clin Pharmacol Ther 66(3) 246-257 (1999). 

Table 1.10 presents a sample table of contents for a modeling report used in support of a pharmacokinetic-pharmacodynamic analysis. The order of the report follows that of a scientific paper introduction, methods, results, and discussion. Within each section, the relevant aspects related to the model are presented. For example, within the discussion section, how plausible the model is,... 

Wahlby, U., Jonsson, E.N., and Karlsson, M.O. Comparison of stepwise covariate model building strategies in population pharmacokinetic-pharmacodynamic analysis. AAPS PharmSci 2002 4 Article 27. 

Mould, D. et al., A population pharmacokinetic-pharmacodynamic analysis of single doses of clenoliximab in patients with rheumatoid arthritis, Clin. Pharmacol. Ther, 66 246-257, 1999. 

Derendorf, H. et al.. Receptor-based pharmacokinetic-pharmacodynamic analysis of corticosteroids, J. Clin. Pharmacol, 33 115-123, 1993. 

Katashima M, Yamamoto K, Tokuma Y, et al. Comparative pharmacokinetic/pharmacodynamic analysis of proton pump inhibitors omeprazole, lansoprazole and pantoprazole, in humans. Eur J Drug Metab Pharmacokinet 1998 23 19-26. 

O. A. Salach, S. Hadad, A. Haj-Yehia, S. Sussan, M. Bialer, Comparative Pharmacokinetic and Pharmacodynamic Analysis of Phthaloyl Glycine Derivatives with Potential Antiepileptic Activity , Pharm. Res. 1994, 11, 1429-1434. 

Elizabetli, C.M., Della, P., Oscar Ploeger, B.A. and Voskuyl, R.A. (2007) Mechanism-based pharmacokinetic-pharmacodynamic modeling hiophase distribution, receptor theory, and dynamical systems analysis. Annual Review of Pharmacology and Toxicology, 47, 357-400. 

As an example, Hsieh et al. identified toxicodynamic biomarkers in monkey semm that demonstrated a quantitative relationship with drug exposure (Cr iax, AUC) and related pathological events [148], The biomarkers were used for a more precise calculation of the no observed adverse effect level (NOAEL). The safety of three different dosing schedules was predicted using pharmacokinetic pharmacodynamic (PKPD) modeling and biomarker analysis. 

This section deals with the question of whether there are quantitatively detectable and interpretable correlations between the dose of an administered drug, or the concentration of a drug and its metabolites measured in the blood or plasma (blood or plasma level), and the therapeutic action or side effects observed. Investigations relating to questions of this type are called PK PD (pharmacokinetic pharmacodynamic) studies. The PK PD analysis is a bidirectional approach pharmacokinetics represent what the body does with a drug, and pharmacodynamics describes what a drug does to the body. The PK PD analyses are key elements of early drug development, and PK PD trials are able to answer specific disease-related efficacy and safety questions. 

Key Words pharmacogenetics pharmacogenomics pharmacokinetics pharmacodynamics polymorphisms candidate gene approaeh pathway analysis genomewide sean... 

Danhof, M., de Jongh, J., De Lange, E. C., Della Pasqua, O., Ploeger, B. A., Voskuyl, R. A. Mechanism-based pharmacokinetic-pharmacodynamic modeling biophase distribution, receptor theory, and dynamical systems analysis. Anna Rev Pharmacol Toxicol 2007,47 357-400. 

Nestorov, I. A. Sensitivity analysis of pharmacokinetic and pharmacodynamic models in clinical trial simulation and design. In Kimko, H. C., Duffull, S. B eds. Simulation for designing clinical trials. A pharmacokinetic-pharmacodynamic modeling perspective. (Drugs and the pharmaceutical sciences, volume 127) Marcel Dekker, New York, 2003. 

---