Abstract
1. The objective of this study was to characterize the pharmacokinetics of isoforskolin after oral, intraperitoneal and intravenous administration, as well as to compare bioavailability.2. Isoforskolin was administered to guinea pigs at a dose of 2 mg/kg. Plasma concentrations were determined by high-performance liquid chromatography–electrospray ionization–tandem mass spectrometry (HPLC–ESI–MS/MS) method. The pharmacokinetic parameters were calculated by a noncompartmental method. A compartment model was also adopted to describe the pharmacokinetic profiles.3. The pharmacokinetic behavior of intravenously administered isoforskolin was characterized by rapid and extensive distribution (Vz = 16.82 ± 8.42 L/kg) followed by rapid elimination from the body (Cl = 9.63 ± 4.21 L/kg/h). After intraperitoneal administration, isoforskolin was absorbed rapidly (Tmax = 0.12 ± 0.05 h). The pharmacokinetic profiles of isoforskolin were similar after intraperitoneal and intravenous administration, except for the concentrations at the initial sampling times. Isoforskolin was also absorbed rapidly following oral dosing; however, the concentration–time data were best fit to a one-compartment model, which was different from that observed after intravenous and intraperitoneal administration. Following intraperitoneal and oral administration, the absolute bioavailability of isoforskolin was 64.12% and 49.25%, respectively.4. Isoforskolin is a good candidate for oral administration because of its good oral bioavailability.
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