Pharmacokinetics of lopinavir after administration of Kaletra in healthy Japanese volunteers.
The pharmacokinetic parameters of lopinavir (LPV) were examined by administering Kaletra (LPV+ritonavir) to 8 healthy Japanese volunteers both in the fasting and postprandial conditions. LPV showed a biphasic decline, which was slower in the initial phase and became more rapid in the later phase. The behavior of LPV in the initial phase could be modeled using a one-compartment model with first-order absorption. In the fasting study, calculations based on the pharmacokinetic model revealed that the time to reach the maximum concentration (T(max)), maximum concentration (C(max)), half-life (T(1/2)), lag time, apparent volume of distribution (Vd/F) and oral clearance (Cl/F) were 3.2+/-1.0 h, 6.9+/-1.9 microg/ml, 10.0+/-3.7 h, 0.71+/-0.32 h, 51.0+/-12.4 l and 4.2+/-2.6 l/h, respectively. On the other hand, in the postprandial study, the calculated T(max), C(max), T(1/2), lag time, Vd/F and Cl/F were 5.6+/-2.0 h, 7.6+/-1.8 microg/ml, 16.7+/-7.0 h, 2.35+/-0.78 h, 48.0+/-15.9 l and 2.1+/-0.6 l/h, respectively. The values for the area under the curve for data collected over a 24-h period (AUC(24 h)) in the fasting and postprandial studies were 86.0+/-27.7 and 102.1+/-31.0 microg.h/ml, respectively. The T(1/2) had a tendency to be prolonged after food intake, but there were 2 cases with shortened T(1/2). Food intake prolonged the lag time 3-fold and as a result, the postprandial T(max) was 2 times longer.
Oki
Tsuyoshi
T
Department of Pharmacy, Nagoya National Hospital (Tokai Area Central Hospital for AIDS Treatment and Research), 4-1-1 Sannomaru, Naka-ku, Nagoya, Aichi 460-0001, Japan.
Usami
Yoshiko
Y
Nakai
Masahiko
M
Sagisaka
Masafumi
M
Ito
Hirotaka
H
Nagaoka
Koichi
K
Mamiya
Naoto
N
Yamanaka
Katsuo
K
Utsumi
Makoto
M
Kaneda
Tsuguhiro
T
D000284:Administration, Oral; D000328:Adult; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D018565:Food-Drug Interactions; D006801:Humans; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D019518:Postprandial Period; D011480:Protease Inhibitors / Q000097:blood / Q000493:pharmacokinetics*; D011744:Pyrimidinones / Q000097:blood / Q000493:pharmacokinetics*; D019438:Ritonavir / Q000493:pharmacokinetics*; D013997:Time Factors
D004338:Drug Combinations; D011480:Protease Inhibitors; D011744:Pyrimidinones; D061466:Lopinavir; D019438:Ritonavir