| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2479071 | Drug Metabolism and Pharmacokinetics | 2010 | 8 Pages |
Summary:To investigate the pharmacokinetics and mechanism of intestinal absorption of JBP485 in rats, the pharmacokinetics of JBP485 were investigated in vivo both intravenously and orally. The effects of glycylsarcosine (Gly-Sar) on the uptake and transepithelial transport of JBP485 were examined in everted intestinal sacs, in situ jejunal perfusion, Caco-2 cells and PEPT1 transfected Hela cells. The gastrointestinal absorption of JBP485 was rapid. T1/2β was 2.25 ± 0.06 h, CLplasma was 2.99 ± 0.002 ml/min/kg, Vd was 0.22 ± 0.05 l/kg and bioavailability was about 30% at a dosage of 25 mg/kg. JBP485 underwent rapid distribution in the tissues. Gly-Sar significantly decreased JBP485 uptake and transport in these models. A kinetic study showed that JBP485 was transported by PEPT1 in Caco-2 cells with Km and Vmax values of 0.33 ± 0.13 mM and 0.72 ± 0.06 nmol/mg protein/10 min, respectively. JBP485 appeared to have linear pharmacokinetics at intravenous doses of 6.25-100 mg/kg with minor first-pass effect, and JBP485 was mainly distributed in the kidney; JBP485 is a substrate for PEPT1 which is involved in the absorption of JBP485 in rat intestine.
