Pharmacokinetics of nelfinavir in subjects with hepatic impairment

HIV-seronegative subjects with hepatic impairment (6 mild, 6 moderate) and 12 matched healthy controls received nelfinavir 1250 mg every 12 hours with food for 2 weeks. Mild impairment did not significantly change nelfinavir or major metabolite (M8) steady-state exposures compared with controls. In subjects with moderate impairment, steady-state area under the plasma concentration time-curve over the dosing interval and maximum observed plasma concentrations were 62% and 22% higher for nelfinavir than for controls, and for M8 were 46% and 35% of control values. With increasing degree of impairment, no trend toward increase in unbound nelfinavir was observed, but there was an increase in unbound M8 levels. Nelfinavir was safe and well tolerated. One subject with moderate impairment was discontinued because of transient leucopenia. Observed changes are unlikely to affect nelfinavir efficacy or markedly influence safety. Dose reduction of nelfinavir does not appear necessary for subjects with mild/moderate impairment. Further long-term evaluations of nelfinavir pharmacokinetics and safety in HIV-seropositive subjects with hepatic impairment may be useful.