Using enzyme inducers to reduce the half-life of nevirapine
11 June 2006. Related: Conference reports, PK Workshop 7th 2006.
Polly Clayden, HIV i-Base
Several studies have reported the development of resistance to nevirapine even after taking a single dose of the drug, which is commonly used in the resource-limited setting for the prevention of mother to child transmission. This is likely due to the long half-life of nevirapine that results in the drug being found in blood for many days after taking the one dose.
A poster from Rafaella Lhomme and coworkers from the Radboud University Nijmegen Medical Centre presented findings from a study exploring the novel strategy of using enzyme inducers to reduce nevirapine half-life and thereby reduce the risk of developing resistance.
This small study evaluated the use of several different strategies including using carbamazepine, phenobarbital, phenytoin, St. Johns Wort tea, retinyl palmitate and beta-carotene, and cholecalciferol.
This was a phase-I single-centre, open-label, two period, nine-group, PK study. A single 200 mg dose of nevirapine was administered to 36 HIV negative non-pregnant women in both period 1 and 2, blood samples were taken twice weekly for 21 days. In period 2 additional interventions (single dose carbamazepine, phenobarbital or phenytoin; phenytoin for 3 or 7 days; St Johns Wort, vitamin A or cholecalciferol for 14 days) were administered to all participants except for the control group. The primary end point was the ratio of nevirapine half-life in period 2 to nevirapine half-life in period 1.
Three of the interventions resulted in the half-life of nevirapine being significantly reduced. These included a single 400mg dose of carbamazepine (p=0.002), once a day 184mg phenytoin for three days (p=0.001) and once a day 184mg phenytoin for seven days (p=0.002). The half-life of nevirapine was reduced by 35.3%, 38.2% and 35.9% respectively. This resulted in a 4.5 8.8 day reduction in time to when nevirapine could not be detected in blood. The other five interventions had no effect on the nevirapine half-life.
These interventions now need to be studied in the real world setting to determine if this will lead to a decreased risk of developing resistance to nevirapine among pregnant women taking single dose nevirapine to prevent HIV transmission to their newborns.
Reference:
Lhomme R, Dijkema T, A. van der Ven A et al. Enzyme inducers reduce nevirapine half-life. 7th International Workshop on Clinical Pharmacology of HIV Therapy, 20-22 April 2006, Lisbon. Abstract 5.