The association between cigarette smoking and efavirenz plasma concentration using the population pharmacokinetic approach

Abstract

Aims Efavirenz is still widely used as the preferred first‐line antiretroviral agent in middle‐ and low‐income countries, including Malaysia. The efavirenz population pharmacokinetic profile among HIV‐positive smokers is still unknown. We aimed to assess the association of smoking with efavirenz and the differences in HIV clinical outcomes. Methods A total of 154 stable HIV‐positive patients on efavirenz in northern Malaysia were recruited with a sparse sampling for this multicentre prospective cohort study. The association between smoking and efavirenz pharmacokinetic parameters was determined using the nonlinear mixed‐effect model. A mixture model of clearance was adopted to describe the metaboliser status because genetic data are unavailable. The effect of smoking on HIV clinical markers (CD4, CD4/CD8 ratio and viral blips) for at least 2 years after the antiretroviral initiation was also investigated. Results Our data were best fitted with a 1‐compartment mixture model with first‐order absorption without lag time. Smoking significantly associated with higher clearance (β = 1.39; 95% confidence interval: 1.07 to 1.91), while weight affected both clearance and volume. From the mixture model, 20% of patients were in the slow clearance group, which mimic the genotype distribution of slow metaboliser. An efavirenz dose reduction is not recommended for smokers ≥60 kg with normal metabolism rate. Smoking significantly associated with slower normalisation of CD4 and CD4/CD8 ratio. Conclusions HIV‐positive smokers presented with significantly higher efavirenz clearance and unfavourable clinical outcomes. Close monitoring of adherence and clinical response among smokers is warranted.

Effects of rifampicin, CYP2B6 and ABCB1 polymorphisms on efavirenz plasma concentration in Chinese patients living with HIV and tuberculosis

“…30 The difference might be caused by a longer sample collection time post efavirenz administration (13.8 h VS 12.0 h), in addition, a higher body weight (63.0 kg VS 60 kg) compared to Guo’s study, and a higher proportion of patients with extensive metabolizer compared to Lee’s study ( CYP2B6 516 GG: 69.3% VS 66.0%). The efavirenz C 0 was consistent with the STRIDE study consisting of multiple ethnicities around the world, 10 slightly higher than 1.70 μg/mL reported in Malay 41 and 1.58 μg/mL in Papua New Guinea population, 42 but lower than 2.32 μg/mL in Thai. 43 The gene polymorphism and different populations seemed to be the main reason.…”

systematic-review-of-population-pharmacokinetic-models-of-isoniazid-in-children-and-adults-with-tuberculosis

“…Nevertheless, incorporating genetic factors in routine clinical practice may not be feasible in some countries. The application of a mixture model to cater to the unavailability of genetic data could assist in quantifying and specifying different acetylation, which is also applied and described for other drugs [34,35].…”