The Use of WinNonlin for The Use of WinNonlin for Determining Basic Determining Basic Pharmacokinetic Pharmacokinetic

ParametersParameters

By Christopher J. Kemper, Ph.D.By Christopher J. Kemper, Ph.D.PharmaPharma Navigators, LLCNavigators, LLC

OverviewOverview

Basic concepts in Pharmacokinetics Basic concepts in Pharmacokinetics and the Big 7and the Big 7The origins of The origins of NonlinNonlin•• Citrix space Citrix space

Available manuals and publicationsAvailable manuals and publicationsStep by step processing of a sample Step by step processing of a sample data setdata set

Pharmacokinetic Parameters: Pharmacokinetic Parameters: Non CompartmentalNon Compartmental

CCmaxmax, , TTmaxmax, AUC, AUC•• AUC = AUC = ∫∫ C C dtdt

Dose/AUC = Dose/AUC = ClClsyssys = = Vol_DistVol_Dist x x λλzz

HalflifeHalflife = 0.693 / = 0.693 / λλzz

MRT = AUMC/AUCMRT = AUMC/AUC•• AUMC = AUMC = ∫∫ tCtC dtdt•• The mean residence time represents the The mean residence time represents the

time for 63.2% of the dose to be time for 63.2% of the dose to be eliminatedeliminated