Pharmacokinetics dosage regimen design

Pharmacokinetics and Drug Dosage Regimen Design—A Possible Application Requiring Construction and Manipulation of a Complex Model and Data Base with an Expert System... 

In conclusion, robust population pharmacokinetic models may contribute to the mechanistic understanding of the fate of mAbs in the body. Factors that may influence the pharmacokinetics of mAbs should be investigated for their potential influence on dosage regimen design in clinical trials and therapeutic use. 

DeVane, C.L. Jusko, W.J. Dosage regimen design. In Pharmacokinetics Theory and Methodology Rowland, M., Tucker, G., Eds. Pergamon Press Oxford, UK, 1986 213-233. 

Determines patient-specific pharmacokinetic parameters on the basis of measured drug concentrations and prospectively applies these data to dosage regimen design. 

Koup JR, Jusko WJ, Elwood CM, KohU RK. Digoxin pharmacokinetics Role of renal failure in dosage regimen design. CUn Pharmacol Ther 1975 18 9-21. 

Population pharmacokinetic parameters quantify population mean kineticS/ between-subject variability (intersubject variability)/ and residual variability. Residual variability includes within-subject variability/ model misspecification/ and measurement error. This information is necessary to design a dosage regimen for a drug. If all patients were identical/ the same dose would be appropriate for all. However/ since... 

Benet, L.Z. Sheiner, L.B. Design and optimization of dosage regimens pharmacokinetic data. In The Pharmacological Basis of Therapeutics, 7th Ed. Gillman, A.G., Ed. Macmillan Publishing Co. New York, 1985 1663-1733. 

Interprets and applies population pharmacokinetic data to the design of patient-specific drug dosage regimens. 

In a pharmacokinetic study in HIV-positive subjects designed to determine the dose of atovaquone suspension that would achieve specific steady-state plasma levels, administration with high-fat food increased the bioavailability of atovaquone by 1.4-fold when compared with the fasted state. In another similar study, administration of atovaquone suspension with food (23 g of fat) increased average steady-state levels by 1.3-fold to 1.7-fold with different dosage regimens (using 500 mg to 1.5 g of atovaquone. ... 

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