Short-term fasting alters cytochrome P450-mediated drug metabolism in humans

Drug Metabolism and Disposition : the Biological Fate of Chemicals
Laureen A LammersRon A A Mathôt

Abstract

Experimental studies indicate that short-term fasting alters drug metabolism. However, the effects of short-term fasting on drug metabolism in humans need further investigation. Therefore, the aim of this study was to evaluate the effects of short-term fasting (36 h) on P450-mediated drug metabolism. In a randomized crossover study design, nine healthy subjects ingested a cocktail consisting of five P450-specific probe drugs [caffeine (CYP1A2), S-warfarin (CYP2C9), omeprazole (CYP2C19), metoprolol (CYP2D6), and midazolam (CYP3A4)] on two occasions (control study after an overnight fast and after 36 h of fasting). Blood samples were drawn for pharmacokinetic analysis using nonlinear mixed effects modeling. In addition, we studied in Wistar rats the effects of short-term fasting on hepatic mRNA expression of P450 isoforms corresponding with the five studied P450 enzymes in humans. In the healthy subjects, short-term fasting increased oral caffeine clearance by 20% (P = 0.03) and decreased oral S-warfarin clearance by 25% (P < 0.001). In rats, short-term fasting increased mRNA expression of the orthologs of human CYP1A2, CYP2C19, CYP2D6, and CYP3A4 (P < 0.05), and decreased the mRNA expression of the ortholog of CYP2C9 (P < 0.001)...Continue Reading

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Citations

Apr 19, 2016·Journal of Clinical Pharmacology·Claudia Stöllberger, Josef Finsterer
Sep 21, 2017·European Journal of Drug Metabolism and Pharmacokinetics·Laureen A LammersRon A A Mathôt
Nov 22, 2018·European Journal of Clinical Pharmacology·Yoshiki KatadaKazuo Matsubara
Dec 19, 2019·Expert Opinion on Drug Metabolism & Toxicology·Laureen A LammersJohannes A Romijn
Oct 21, 2016·Therapeutic Drug Monitoring·Laureen A LammersRon A A Mathôt
Dec 2, 2019·Biochemical Pharmacology·Rebekka ThøgersenMartin Krøyer Rasmussen
Sep 6, 2021·International Journal of Clinical Practice·Abdulrahman AlwhaibiMohamed Al-Arifi

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