The rate of gastric emptying determines the timing but not the extent of oral tacrolimus absorption: simultaneous measurement of drug exposure and gastric emptying by carbon-14-octanoic acid breath test in stable renal allograft recipients

Drug Metabolism and Disposition : the Biological Fate of Chemicals
Dirk R J KuypersYves Vanrenterghem

Abstract

Tacrolimus is characterized by a highly variable oral bioavailability and narrow therapeutic window. Tacrolimus absorption from the gastrointestinal tract is to a large extent determined by the genotypic, phenotypic, and functional expression of P-glycoprotein and CYP3A in the gut wall and liver. It is disputed whether the gastric emptying rate per se is important for determining oral bioavailability of tacrolimus and whether delayed gastric emptying is clinically relevant for therapeutic drug dosing. We conducted a pharmacokinetic study in 50 renal recipients, measuring simultaneously the rate of gastric emptying using a carbon-14-octanoic acid breath test and quantifying drug exposure by area under the concentration-time curve sampling. Gastric half emptying time (t1/2) significantly correlated with time to reach maximum blood tacrolimus (tmax) concentration (r2 = 0.30; p < 0.0001), whereas the gastric emptying coefficient, reflecting the overall gastric emptying rate, showed a weak inverse correlation with tmax (r2 = 0.14; p = 0.007). The time-dependent rate of gastric emptying strongly correlated with the simultaneously measured blood tacrolimus concentration over the first 4 h after oral drug administration (r2 = 0.96; p <...Continue Reading

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Citations

Sep 12, 2006·Digestive Diseases and Sciences·Yago Gonzalez-LamaJose Mate
Feb 26, 2016·Drug Metabolism Reviews·Thomas VanhoveDirk R J Kuypers
Nov 11, 2006·British Journal of Clinical Pharmacology·Maarten NaesensDirk Kuypers
Dec 19, 2014·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·R Sapir-PichhadzeS J Kim
Aug 26, 2014·Digestive Diseases and Sciences·Maria do Carmo B TeixeiraLuciana A Corá
Sep 17, 2013·Neuropharmacology·Mark Halliday, Giovanna R Mallucci
Nov 15, 2019·British Journal of Clinical Pharmacology·Guo-Xiang HaoWei Zhao
May 27, 2020·Therapeutic Drug Monitoring·Rita R AllowayJeremiah D Momper
Sep 16, 2020·European Journal of Cardio-thoracic Surgery : Official Journal of the European Association for Cardio-thoracic Surgery·Philipp AngleitnerArezu Z Aliabadi-Zuckermann
Mar 1, 2021·Clinical Pharmacology in Drug Development·Andrea HuppertzDavid Czock
Aug 20, 2021·Expert Opinion on Drug Metabolism & Toxicology·Eleni Aklillu, Ephrem Engidawork

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