Pharmacokinetics and Mechanism of Intestinal Absorption of JBP485 in Rats

被引：28

作者：

Cang, Jian ^{[1
]}

Zhang, Jian ^{[1
]}

Wang, Changyuan ^{[1
]}

Liu, Qi ^{[1
]}

Meng, Qiang ^{[1
]}

Wang, Desheng ^{[2
]}

Sugiyama, Yuichi ^{[2
]}

Tsuji, Akira ^{[3
]}

Kaku, Taiichi ^{[4
]}

Liu, Kexin ^{[1
]}

机构：

[1] Dalian Med Univ, Dept Clin Pharmacol, Coll Pharm, 9 W Sect,Lvshun S Rd, Dalian 116044, Peoples R China

[2] Univ Tokyo, Grad Sch Pharmaceut Sci, Tokyo, Japan

[3] Kanazawa Univ, Fac Pharmaceut Sci, Grad Sch Nat Sci & Technol, Kanazawa, Ishikawa 920, Japan

[4] Japan Bioprod Ind Co Ltd, Tokyo, Japan

来源：

DRUG METABOLISM AND PHARMACOKINETICS | 2010年 / 25卷 / 05期

基金：

中国国家自然科学基金;

关键词：

JBP485; dipeptide; PEPT1; Glycylsarcosine; Pharmacokinetics; H+/PEPTIDE SYMPORTER PEPT1; TRANSPORT; CACO-2; AFFINITY;

D O I：

10.2133/dmpk.DMPK-10-RG-045

中图分类号：

R9 [药学];

学科分类号：

100702 [药剂学];

摘要：

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 He la cells. The gastrointestinal absorption of JBP485 was rapid T-1/2 beta was 2 25 +/- 0 06 h. CLplasma was 2 99 +/- 0 002 ml/min/kg, V-d 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.

引用

页码：500 / 507

页数：8

共 23 条

[1]

The renal type H+/peptide symporter PEPT2:: structure-affinity relationships [J].