The steady-state pharmacokinetics of efavirenz and nevirapine when used incombination in human immunodeficiency virus type 1-infected persons

The steady-state pharmacokinetics of efavirenz and nevirapine, when used in combination to treat human immunodeficiency virus type 1 (HIV-1)-infected subjects, were investigated. HIV-1-infected persons who had used efavirenz (600 mg once daily) for greater than or equal to2 weeks were eligible for s tudy inclusion. The plasma pharmacokinetics of efavirenz were determined ov er 24 h. Subsequently, nevirapine (400 mg once daily) was added to the regi men. After 4 weeks, the pharmacokinetics of efavirenz and nevirapine were a ssessed over 24 h. The differences between the pharmacokinetic parameters o f efavirenz with and without nevirapine were analyzed, and the pharmacokine tics of nevirapine were compared with those in historical control patients. The exposure to efavirenz when combined with nevirapine was significantly decreased by 22% (area under the plasma concentration vs. time curve), 36% (minimum plasma concentration), and 17% (maximum plasma concentration). Nev irapine pharmacokinetics appear to be unaffected by coadministration of efa virenz, compared with data from historical control patients.