Reports from Vertex Pharmaceuticals Describe Recent Advances in Pharmacokinetics (In Vitro and In Vivo Mechanistic Studies toward Understanding the Role of 1-Aminobenzotriazole in Rat Drug-Drug Interactions)
By a News Reporter-Staff News Editor at Drug Week -- A new study on Pharmacokinetics is now available. According to news reporting out of Laval, Canada, by NewsRx editors, research stated, "1-Aminobenzotriazole (ABT) is regularly used in vivo as a nonspecific and irreversible cytochrome P450 inhibitor to elucidate the role of metabolism on the pharmacokinetic profile of xenobiotics. However, few reports have considered the recent findings that ABT can alter drug absorption or have investigated the possible differential inhibition of ABT on intestinal and hepatic metabolism."
Our news journalists obtained a quote from the research from Vertex Pharmaceuticals, "To address these uncertainties, pharmacokinetic studies under well controlled and defined ABT pretreatment conditions (50 mg/kg, 1 hour ABT i.v. and 16 hours ABT p.o.) were conducted prior to the oral administration of metoprolol, a permeable P450 probe that undergoes extensive intestinal and hepatic metabolism. The pharmacokinetic profile of metoprolol was affected differently by the two ABT pretreatments. An increase in area under the curve of 16-fold with ABT p.o. and 6.5-fold with ABT i.v. was observed compared with control. Based on in vitro studies, this difference could not be attributed to a differential inhibition of intestinal and hepatic metabolism. In the ABT i.v. pretreatment group, the increase in area under the curve was also associated with a prolonged time at maximal concentration (24-fold versus control), suggesting a delay in absorption. This was further confirmed by the administration of a charcoal meal, which resulted in a 7-fold increase in stomach weights in the 1-hour ABT pretreated groups compared with the untreated or 16-hour ABT pretreated rats."
According to the news editors, the research concluded: "Based on these results, we recommend pretreating rats with ABT p.o. 16 hours before the administration of a test compound to preserve the inhibitory effect on intestinal and hepatic metabolism and avoid the confounding effect on drug absorption."
For more information on this research see: In Vitro and In Vivo Mechanistic Studies toward Understanding the Role of 1-Aminobenzotriazole in Rat Drug-Drug Interactions. Drug Metabolism and Disposition, 2015;43(12):1960-1965. Drug Metabolism and Disposition can be contacted at: Amer Soc Pharmacology Experimental Therapeutics, 9650 Rockville Pike, Bethesda, MD 20814-3995, USA (see also Pharmacokinetics).
Our news journalists report that additional information may be obtained by contacting M.O. Boily, Vertex Pharmaceut Canada Inc, Laval, PQ, Canada. Additional authors for this research include N. Chauret, J. Laterreur, F.A. Leblond, C. Boudreau, M.C. Duquet, J.F. Levesque, L. Ste-Marie and V. Pichette.
Keywords for this news article include: Laval, Quebec, Canada, North and Central America, Pharmacokinetics, Pharmaceuticals, Therapy, Drugs, Vertex Pharmaceuticals.
Our reports deliver fact-based news of research and discoveries from around the world. Copyright 2016, NewsRx LLC