pH dependent uptake of loperamide across the gastrointestinal tract: an in vitro study

Drug Development and Industrial Pharmacy
Andrew Crowe, Penny Wong

Abstract

Loperamide is a peripherally acting antidiarrheal opioid with some affinity for P-glycoprotein (P-gp). One of the main reasons for its lack of central nervous system (CNS) activity is a combination first-pass metabolism and P-gp-mediated efflux preventing brain penetration. It was assumed that P-gp would also have a similar effect at the intestinal tract, limiting loperamide systemic absorption. However, previous in vitro studies had not determined loperamide flux using pH gradients present in the intestinal tract. Hence, our aim was to determine the influence of pH gradient conditions on the gastrointestinal uptake of loperamide, including any changes to its P-gp-mediated efflux. Cellular uptake and transcellular transport were determined after exposure to various concentrations of loperamide (2-50 microM) with and without the presence of active efflux protein inhibitors. Loperamide was detected at 214 nm using high-performance liquid chromatography (HPLC) protocols. Bidirectional transport studies of 10 microM loperamide with a pH 6.0/7.4 apical (Ap)-to-basolateral (Bas) gradient showed efflux to be 17-fold higher than influx (10 ng/cm2/min Bas-->Ap compared to 0.6 for Ap-->Bas). This differential was much greater than when e...Continue Reading

References

Jun 20, 1990·The American Journal of Medicine·C D Ericsson, P C Johnson
Mar 1, 1995·British Journal of Pharmacology·D T ThwaitesN L Simmons
Jun 1, 1993·Digestive Diseases and Sciences·F AwoutersP A Janssen
Jun 1, 1996·Pharmaceutical Research·K I HosoyaV H Lee
Jul 1, 1996·Pharmaceutical Research·A Tsuji, I Tamai
Jun 1, 1997·Seminars in Cancer Biology·A H Schinkel
May 20, 1999·Annual Review of Pharmacology and Toxicology·S V AmbudkarM M Gottesman
Oct 3, 2000·Clinical Pharmacology and Therapeutics·A J SadequeA J Wood
Nov 24, 2001·Clinical Pharmacology and Therapeutics·Y TayrouzG Mikus
Nov 14, 2003·Toxicology and Applied Pharmacology·Andrew Crowe, Penny Wong

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Citations

Aug 19, 2006·Antimicrobial Agents and Chemotherapy·Andrew CroweTimothy M E Davis
Jul 22, 2008·European Journal of Pharmacology·Andrew Crowe, Susanna Diep
Jun 6, 2009·Basic & Clinical Pharmacology & Toxicology·Mouna KanaanJules Desmeules
Aug 20, 2019·Expert Review of Clinical Pharmacology·Justin P Reinert, Rebecca L Dunn
Jan 18, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Susan E PrattAnne H Dantzig
Jul 11, 2020·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Angela EffingerNikoletta Fotaki
Nov 28, 2006·Journal of Chemical Information and Modeling·Grégori Gerebtzoff, Anna Seelig

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