Effect of gender, race and genotype on interpatient variability in the pharmacokinetics of efavirenz

Abstract

Background/Aims There is large interpatient variability in the pharmacokinetics of the HIV non-nucleoside reverse transcriptase inhibitor efavirenz, often leading to subtherapeutic (<1.0 mg/L) or toxic (>4.0 mg/L) efavirenz plasma levels. We investigated a range of factors possibly underlying the interpatient variability of efavirenz plasma levels. Methods In this retrospective multicenter study, efavirenz plasma levels were measured in 255 patients included in our national Therapeutic Drug Monitoring service. Information on gender, age, weight, length, race and hormonal contraceptive use was recorded, and subjects were genotyped for CYP2B6 C1459T (corresponding to decreased activity) using PCR-RFLP. Differences in plasma levels between subgroups were compared by analysis of variance and regression analysis. Results Gender and race were significantly associated with the efavirenz plasma level in a multivariate analysis. The mean± SD plasma level in females was 4.0±3.2 vs. 2.8±1.7 mg/L in males (P<0.001). In Asians (n=10), blacks (n=84) and Caucasians (n=161), mean efavirenz plasma levels were 3.3±1.6, 3.8±3.0 and 2.8±1.6 mg/L, respectively (P=0.003). There was no significant influence for weight, contraceptive use or the CYP2B6 SNP. Conclusions Gender and race are important factors determining the interpatient variability in efavirenz plasma levels, but there was no effect of the CYP2B6 SNP C1459T. Clinical Pharmacology & Therapeutics (2005) 77, P42–P42; doi: 10.1016/j.clpt.2004.12.054