Pharmacokinetics of lopinavir after administration of Kaletra in healthy Japanese volunteers

Abstract

The pharmacokinetic parameters of lopinavir (LPV) were examined by administering Kaletra (LPV1ritonavir) 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 (Tmax), maximum concentration (Cmax), half-life (T1/2), lag time, apparent volume of distribution (Vd/F) and oral clearance (Cl/F) were 3.2±1.0 h, 6.9±1.9 μg/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 Tmax, Cmax, T1/2, lag time, Vd/F and Cl/F were 5.6±2.0 h, 7.6±1.8 μg/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 (AUC24 h) in the fasting and postprandial studies were 86.0±27.7 and 102.1±31.0 μg • h/ml, respectively. The T1/2 had a tendency to be prolonged after food intake, but there were 2 cases with shortened T1/2. Food intake prolonged the lag time 3-fold and as a result, the postprandial Tmax was 2 times longer. © 2004 Pharmaceutical Society of Japan.