We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Pharmacokinetics of the nonnucleoside reverse transcriptase inhibitor efavirenz among HIV-infected Ugandans.
- Authors
Nanzigu, S; Eriksen, J; Makumbi, F; Lanke, S; Mahindi, M; Kiguba, R; Beck, O; Ma, Q; Morse, GD; Gustafsson, LL; Waako, P
- Abstract
Background Pharmacokinetic variability of the nonnucleoside reverse transcriptase inhibitor efavirenz has been documented, and high variation in trough concentrations or clearance has been found to be a risk for virological failure. Africans population exhibits greater variability in efavirenz concentrations than other ethnic groups, and so a better understanding of the pharmacokinetics of the drug is needed in this population. This study characterized efavirenz pharmacokinetics in HIV-infected Ugandans. Methods Efavirenz plasma concentrations were obtained for 66 HIV-infected Ugandans initiating efavirenz- based regimens, with blood samples collected at eight time-points over 24 h on day 1 of treatment, and at a further eight time-points on day 14. Noncompartmental analysis was used to describe the pharmacokinetics of efavirenz. Results The mean steady-state minimum plasma concentration ( Cmin) of efavirenz was 2.9 µg/mL, the mean area under the curve (AUC) was 278.5 h µg/mL, and mean efavirenz clearance was 7.4 L/h. Although overall mean clearance did not change over the 2 weeks, 41.9% of participants showed an average 95.8% increase in clearance. On day 14, the maximum concentration ( Cmax) of efavirenz was >4 µg/mL in 96.6% of participants, while Cmin was <1 µg/mL in only 4.5%. Overall, 69% of participants experienced adverse central nervous system (CNS) symptoms attributable to efavirenz during the 2-week period, and 95% of these participants were found to have efavirenz plasma concentrations >4 µg/mL, although only half maintained a high concentration until at least 8 h after dosing. Conclusion The findings of this study show that HIV-infected patients on efavirenz may exhibit autoinduction to various extents, and this needs to be taken into consideration in the clinical management of individual patients. Efavirenz CNS toxicity during the initial phase of treatment may be related to Cmax, regardless of the sampling time.
- Subjects
AFRICA; UGANDA; PNEUMOCYSTIS carinii pneumonia treatment; BLACK people; BLOOD cell count; CENTRAL nervous system; DEMOGRAPHY; DRUG toxicity; GENETIC polymorphisms; HIV infections; HIV-positive persons; EVALUATION of medical care; T cells; WEIGHT loss; TREATMENT duration; NUCLEOSIDE reverse transcriptase inhibitors; EFAVIRENZ
- Publication
HIV Medicine, 2012, Vol 13, Issue 4, p193
- ISSN
1464-2662
- Publication type
Article
- DOI
10.1111/j.1468-1293.2011.00952.x