Interpatient variability in the pharmacokinetics of the HIV non-nucleoside reverse transcriptase inhibitor efavirenz: the effect of gender, race, and CYP2B6 polymorphism

Br J Clin Pharmacol. 2006 Feb;61(2):148-54. doi: 10.1111/j.1365-2125.2005.02536.x.


Aims: To characterize the demographic and pharmacogenetic factors that influence interpatient variability in the plasma concentrations of the HIV non-nucleoside reverse transcriptase inhibitor efavirenz.

Methods: Data from all samples analyzed for efavirenz in our TDM service in 2002 and 2003 were reviewed. Information on gender, age, body weight, height, race, hormonal contraceptive use (in a subset of patients), and time between sampling and last intake was recorded. PCR-restriction fragment length polymorphism analysis was performed to detect the cytochrome P450 2B6 (CYP2B6) C1459T variant (present in CYP2B6*6 and CYP2B6*7) which is associated with low CYP2B6 activity.

Results: A total of 255 patients were included in this analysis. The median plasma efavirenz concentration was 2.50 (interquartile range: 1.85-3.55) mg l(-1). Eight patients (3.1%) were considered to have a subtherapeutic plasma concentration (<1.0 mg l(-1)) and 48 (18.9%) a toxic efavirenz concentration (>4.0 mg l(-1)). Gender, time after last intake, and race were the only factors that were significantly related to plasma efavirenz concentration in a multivariate analysis. No influence was observed for body weight, hormonal contraceptive use, and the presence of the CYP2B6 C1459T polymorphism.

Conclusions: Gender and race are important factors in determining interpatient variability in plasma efavirenz concentrations which were unaffected by the presence of the CYP2B6 C1459T polymorphism. Physicians should be particularly alert for signs of efavirenz-induced toxicity in females and non-Caucasian patients.

MeSH terms

  • Adult
  • Alkynes
  • Anthropometry
  • Anti-HIV Agents / blood*
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Benzoxazines
  • Cyclopropanes
  • Cytochrome P-450 CYP2B6
  • Female
  • HIV Reverse Transcriptase / antagonists & inhibitors
  • Humans
  • Male
  • Middle Aged
  • Oxazines / blood*
  • Oxidoreductases, N-Demethylating / genetics*
  • Pharmacogenetics
  • Polymorphism, Single Nucleotide*
  • Racial Groups / genetics*
  • Reverse Transcriptase Inhibitors / blood*
  • Sex Characteristics


  • Alkynes
  • Anti-HIV Agents
  • Benzoxazines
  • Cyclopropanes
  • Oxazines
  • Reverse Transcriptase Inhibitors
  • Aryl Hydrocarbon Hydroxylases
  • CYP2B6 protein, human
  • Cytochrome P-450 CYP2B6
  • Oxidoreductases, N-Demethylating
  • HIV Reverse Transcriptase
  • efavirenz