Abstract

This work seeks to project individual pharmacokinetic (PK) parameter estimates of efavirenz (a drug with a long half life) from mid-dose concentrations and covariates, assuming full mass transfer of the drug. Gender, weight and CYP2B6, 516G>T genetic data of 61 patients on efavirenz containing highly active antiretroviral therapy (HAART) was collated and analysed. Models were derived to guide dose adjustment in patients predicted to have unsafe drug exposure, and new modelling methods and interpretations are suggested to estimate PK parameters. A new measure related to the uptake of the drug is incorporated in modelling of transportation (cumulative uptake volume). The cumulative uptake-volume associated with the full absorption of 600 mg of efavirenz was estimated to be 35.56 L whereas the volume of distribution was found to be 39.68 L. A sufficient relationship was established between estimated absolute oral bioavailability (f) and mid-dose concentration (x) at steady state . Patients who carry the CYP2B6 G516T TT genotype are projected to have high efavirenz exposure. The estimated bioavailability in this population ranges from (0.29; 0.86). Genotype, weight and gender based inference for dose adjustment proposition is evident for the drug efavirenz. The drug is projected to have been fully absorbed in 31 h in this population.

Key words: Efavirenz, cumulative uptake-volume, bioavailability, volume of distribution, area under the curve (AUC), absorption rate.