title: Effects of cysteine on the pharmacokinetics of paclitaxel in rats.
abstract: Paclitaxel is a P-gp substrate and metabolized via CYP2C and 3A subfamily in rats. It has been reported that cysteine causes the changes in expression of CYP isozymes and intestinal P-gp mediated efflux activity in rats. Thus, the effects of cysteine on the pharmacokinetics of intravenous and oral paclitaxel were investigated in rats. After intravenous administration of paclitaxel (30 mg/kg) to control (CON), single cysteine treatment (ST) and cysteine treatment for a week (CT) rats, the pharmacokinetic parameters were comparable among three groups of rats. Also the pharmacokinetic parameters between CON and ST rats were comparable after oral administration of paclitaxel (30 mg/kg) to rats. These results are consistent with that oral cysteine supplement on a single day did not considerably inhibit the metabolism of paclitaxel via hepatic and/or intestinal CYP3A subfamily and P-gp mediated efflux of paclitaxel in the liver and/or intestine both after intravenous and oral administration to rats. After oral administration of paclitaxel (30 mg/kg) to rats, the greater AUC(06 h) in CT rats was mainly due to that oral cysteine supplement for seven consecutive days enhanced the gastrointestinal absorption of paclitaxel compared with those in CON and ST rats.
authors.affiliation: College of Pharmacy, Dongguk University-Seoul, Seoul 100-715, Korea.
authors.forename: Yu Kyung
authors.initials: YK
authors.lastname: Lee
authors.forename: Seung Yon
authors.initials: SY
authors.lastname: Han
authors.forename: Young-Won
authors.initials: YW
authors.lastname: Chin
authors.forename: Young Hee
authors.initials: YH
authors.lastname: Choi
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001711:Biotransformation; D003545:Cysteine / Q000008:administration & dosage / Q000494:pharmacology*; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D004347:Drug Interactions; D007275:Injections, Intravenous; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D008297:Male; D008657:Metabolic Clearance Rate; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D017239:Paclitaxel / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D051544:Cytochrome P-450 CYP3A; D003545:Cysteine; D017239:Paclitaxel