Pharmacokinetics of clofazimine in healthy volunteers.
The pharmacokinetics of clofazimine was evaluated in 12 healthy male volunteers following single and multiple oral doses of clofazimine. Six volunteers received a single dose of 200 mg together with food. A 200-mg dose was administered to three volunteers either with or without food. In a multiple-dose experiment, three volunteers were repeatedly dosed with 50 mg per day together with food for 8 days. Following a single oral dose of 200 mg, the mean peak plasma concentration of clofazimine was 861 +/- 289 pmol/g (+/- S.D., N = 6) after 8 hr (median). The mean terminal half-life was 10.6 +/- 4.0 days. Comparison of the bioavailability of clofazimine administered with or without food revealed a 60% higher mean area under the curve (AUC) value and a 30% higher mean maximum concentration (Cmax) value with food (N = 3). The median of times to peak (Tmax) was 8 hr with food and 12 hr without food. In the multiple-dose study, good agreement was found between the mean experimental plasma concentration values and the plasma concentration profile predicted from the single-dose pharmacokinetics. The elimination half-life calculated from the terminal phase of the individual profiles after the last dose was 8.8 +/- 1.0 days (+/- S.D., N = 3). The half-life obtained from the fitted mean multiple-dose profile was 10.5 days. The slow elimination of clofazimine has its implications for the treatment regimen in patients. To avoid the long-lasting accumulation toward the steady state, higher daily loading doses are recommended at the beginning of therapy followed by a daily maintenance dose.
D000284:Administration, Oral; D000328:Adult; D002991:Clofazimine / Q000008:administration & dosage / Q000378:metabolism*; D005502:Food; D006207:Half-Life; D006801:Humans; D007408:Intestinal Absorption; D007700:Kinetics; D008297:Male; D008875:Middle Aged
D002991:Clofazimine