Kwara, A., Lartey, M., Sagoe, K.W., Xexemeku, F., Kenu, E., Oliver-Commey, J., Boima, V., Sagoe, A., Boamah, I., Greenblatt, D.J. and Court, M.H. (2008) Pharmacokinetics of Efavirenz When Co-Administered with Rifampin in TB/HIV Co-Infected Patients: Pharmacogenetic Effect of CYP2B6 Variation. Journal of Clinical Pharmacology, 48, 1032-1040.
http://dx.doi.org/10.1177/0091270008321790

has been cited by the following article:

• TITLE: Influence of CYP2B6 516G > T and Long Term HAART on Population Pharmacokinetics of Efavirenz in Rwandan Adults on HIV and Tuberculosis Cotreatment

  AUTHORS: Emile Bienvenu, Michael Ashton, Angela Äbelö

  KEYWORDS: Clearance, CYP2B6, Efavirenz, HIV, RBT, Tuberculosis

  JOURNAL NAME: Pharmacology & Pharmacy, Vol.6 No.11, November 25, 2015

  ABSTRACT: Aim: To describe the pharmacokinetic parameters of efavirenz and estimate its clearance (CL/F) accounting simultaneously for drug-drug interactions and CYP2B6 genetic polymorphism. Methods: Genotyping of 516G > T single nucleotide polymorphism of CYP2B6 was performed using a PCR-based technology and plasma efavirenz concentrations were measured by high performance liquid chromatography on blood samples from 76 HIV adults co-infected with tuberculosis who had received an efavirenz-based regimen. Data were analyzed using population modeling with NONMEM. Results: The absorption rate constant and the apparent volume of distribution in the final model were 1.9 h-1 and 580 L/70kg, respectively. The CL/F at baseline was 11.8 L/h/70kg, 8.8 L/h/70kg and 3.9 L/h/70kg for patients carrying the G/G, G/T and T/T genotypes of CYP2B6 516G > T, respectively, in patients who were administered tuberculosis (TB) treatment prior to HIV treatment (Group A); and 16.7 L/h/70kg, 10.6 L/h/70kg and 1.8 L/h/70kg for G/G, G/T and T/T genotype patients respectively, in patients with previous exposure to HIV treatment (Group B). The CL/F at baseline and steady state was always higher in Group B compared to Group A patients. Expectedly, carriers of CYP2B6 516G/G and T/T genotypes exhibited higher and lower CL/F, respectively. Conclusion: Our results indicated that the CL/F of efavirenz in the population studied was predictably different due to whether the patients were mono-treated for TB with HAART deferred or for HIV before initiation of TB therapy, and to CYP2B6 516G > T variant, implying that both CYP2B6 genetic polymorphisms and previous efavirenz-based HAART should be taken into account when adjusting efavirenz dose.