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Sustained Increase in the Oral Bioavailability of Loperamide after a Single Oral Dose of HM30181, a P-glycoprotein Inhibitor, in Healthy Male Subjects.

Basic Clin Pharmacol Toxicol. 2013 Jul 6;

Authors: Cha YJ, Lee H, Gu N, Kim TE, Lim KS, Yoon SH, Chung JY, Jang IJ, Shin SG, Yu KS, Cho JY


HM30181 is a new P-glycoprotein (P-gp) inhibitor. This study was conducted to investigate the effect of HM30181 and its duration of action on P-gp inhibition using loperamide as a probe drug. An open-label, five-period, fixed-sequence, cross-over study was conducted in 25 healthy Korean subjects, who received a single oral dose of loperamide at 16 mg in five periods lasting for 17 days. In period II, subjects also randomly received a single oral dose of HM30181 at 1, 5, 10, 15 mg simultaneously with loperamide. Serial pharmacokinetic blood samples were obtained up to 72 and 336 hr after loperamide and HM30181 administration, respectively. A mixed-effects analysis was performed to compare the area under the plasma concentration versus time curve from time 0 to 72 hr (AUC0-72h ) between periods and HM30181 dose groups. Tolerability was also assessed. The AUC0-72h of repeatedly administered loperamide was significantly increased 1.18-1.62-fold for up to 14 days after a single oral administration of HM30181, particularly at doses ≥10 mg although the between-group difference failed to reach a statistical significance. Plasma HM30181 was not detected in many subjects including none at any sampling points beyond 48 hr after administration. Most adverse events were mild to moderate and resolved spontaneously. The oral bioavailability of loperamide was significantly enhanced by a single oral administration of HM30181, which was sustained for up to 14 days. HM30181 was well tolerated in this selected population. This article is protected by copyright. All rights reserved.

PMID: 23829508 [PubMed - as supplied by publisher]