Current drug metabolism · 2016
Prediction of Plasma Concentration-time Profiles of Drugs in Humans from Animals Following Oral Administration: An Allometric Approach.
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Mahmood Iftekhar
Аннотация
BACKGROUND: Allometric scaling is regularly used for the prediction of human pharmacokinetic (PK) parameters from animal PK studies. The predicted human PK parameters can also be used for the prediction of plasma concentration-time profiles in humans.
OBJECTIVES: The main objective of this work is to predict human concentration-time profiles of drugs (one-compartment model) following oral administration using animal oral pharmacokinetic parameters.
METHODS: Six drugs from the literature were chosen that were described by one-compartment model in both humans and animals following oral administration. Pharmacokinetic parameters such as oral clearance, oral volume of distribution of the central compartment, time to reach maximum plasma concentration, absorption rate constant, and half-life in humans were predicted from animals using allometric scaling. These predicted human pharmacokinetic parameters were then used to predict human plasma concentrations-time profiles of drugs.
RESULTS: The results of this study indicate that the proposed method can be used to predict human plasma concentrations- time profiles of drugs with reasonable accuracy (≤50% prediction error).
CONCLUSIONS: Given the complexity in the pharmacokinetics of oral drugs there remains some uncertainty in this entire exercise. One can minimize the prediction error by experience in allometric scaling, scientific judgment, and unconventional or innovative thinking.
OBJECTIVES: The main objective of this work is to predict human concentration-time profiles of drugs (one-compartment model) following oral administration using animal oral pharmacokinetic parameters.
METHODS: Six drugs from the literature were chosen that were described by one-compartment model in both humans and animals following oral administration. Pharmacokinetic parameters such as oral clearance, oral volume of distribution of the central compartment, time to reach maximum plasma concentration, absorption rate constant, and half-life in humans were predicted from animals using allometric scaling. These predicted human pharmacokinetic parameters were then used to predict human plasma concentrations-time profiles of drugs.
RESULTS: The results of this study indicate that the proposed method can be used to predict human plasma concentrations- time profiles of drugs with reasonable accuracy (≤50% prediction error).
CONCLUSIONS: Given the complexity in the pharmacokinetics of oral drugs there remains some uncertainty in this entire exercise. One can minimize the prediction error by experience in allometric scaling, scientific judgment, and unconventional or innovative thinking.