Studies on intestinal absorption of sulpiride (3): intestinal absorption of sulpiride in rats.
The aim of this study was to investigate whether the concomitant administration of the substrates or inhibitors of PEPT1, OCTN1, OCTN2, and P-glycoprotein affects the intestinal absorption of sulpiride in rats. The absorption of sulpiride from rat intestine was decreased by the substrates or inhibitors of PEPT1, OCTN1, and OCTN2. On the other hand, the absorption was increased by the substrates of P-glycoprotein. The effects of these concomitantly administered drugs on the pharmacokinetic behavior of sulpiride after oral administration in rats were investigated. Peak concentration (C(max)) and area under the plasma concentration-time curve (AUC(0-8 h)) of sulpiride were decreased by the concomitant administration of the substrates or inhibitors of PEPT1, OCTN1, and OCTN2. However, the same parameters were significantly increased by the concomitant administration of the substrates of P-glycoprotein. The present results suggest the possibility of drug-drug interaction during the absorption process in the small intestine due to the coadministration of sulpiride and these agents. These findings provide important information for preventing adverse effects and for ensuring the effectiveness of sulpiride and concomitantly administered drugs.
Watanabe
Kazuhiro
K
Hokkaido College of Pharmacy, 7-1 Katsuraoka-cho, Otaru, Hokkaido 047-0264, Japan. watanabe@hokuyakudai.ac.jp
Sawano
Tetsuya
T
Jinriki
Toshiya
T
Sato
Juichi
J
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004347:Drug Interactions; D007408:Intestinal Absorption; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D027701:Organic Cation Transport Proteins; D027702:Organic Cation Transporter 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000074011:Peptide Transporter 1; D051381:Rats; D017208:Rats, Wistar; D000074058:Solute Carrier Family 22 Member 5; D000070590:Solute Carrier Proteins; D013469:Sulpiride / Q000493:pharmacokinetics*; D027981:Symporters
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018687:Antidepressive Agents, Second-Generation; D002352:Carrier Proteins; D008565:Membrane Proteins; D027701:Organic Cation Transport Proteins; D027702:Organic Cation Transporter 1; D000074011:Peptide Transporter 1; C082186:SLC15A1 protein, human; C492020:SLC22A5 protein, human; C489940:Slc15a1 protein, rat; C000705567:Slc22a4 protein, rat; D000074058:Solute Carrier Family 22 Member 5; D000070590:Solute Carrier Proteins; D027981:Symporters; D013469:Sulpiride