Bibliographic Details
| Title: |
The association between cigarette smoking and efavirenz plasma concentration using the population pharmacokinetic approach. |
| Authors: |
Chow, Ngah Kuan, Harun, Sabariah Noor, Wong, E‐Jinq, Low, Lee Lee, Sheikh Ghadzi, Siti Maisharah, Khan, Amer Hayat |
| Source: |
British Journal of Clinical Pharmacology; Oct2021, Vol. 87 Issue 10, p3756-3765, 10p |
| Subject Terms: |
EFAVIRENZ, CIGARETTE smoke, SMOKING, PHARMACOKINETICS, HIV-positive persons, TREATMENT effectiveness |
| Geographic Terms: |
MALAYSIA |
| 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. [ABSTRACT FROM AUTHOR] |
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| Database: |
Complementary Index |
