Increased Paracetamol Bioavailability after Sleeve Gastrectomy: A Crossover Pre- vs. Post-Operative Clinical Trial

Daniel Porat, Milica Markovic, Moran Zur, Noa Fine-Shamir, Carmil Azran, Gad Shaked, David Czeiger, Julie Vaynshtein, Ilya Replyanski, Gilbert Sebbag, Arik Dahan

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Oral drug bioavailability may be significantly altered after laparoscopic sleeve gastrectomy (LSG), the most popular bariatric procedure worldwide. Paracetamol (acetaminophen) is the post-bariatric analgesic/antipyretic drug of choice. In this work we studied and analyzed the LSG effects on systemic bioavailability and pharmacokinetics of paracetamol after oral administration of solid vs. liquid dosage form. A 4-armed, pharmacokinetic, crossover trial was performed in patients enrolled for LSG. Single paracetamol dose (500 mg), as caplet (n = 7) or syrup (n = 5), was administered before vs. 4-6 months post-LSG. Bioavailability was enhanced after LSG; in the caplet groups, average AUC0-t increased from 9.1 to 18.6 µg·h/mL with AUC0-t difference of 9.5 µg·h/mL (95% CI 4.6-14.5, p = 0.003). Cmax increased from 1.8 (95% CI 1.2-2.5) to 4.2 µg/mL (3.6-4.8) after LSG (p = 0.032). In the syrup groups, AUC0-t increased from 13.4 to 25.6 µg·h/mL, with AUC0-t difference of 12.2 µg·h/mL (95% CI 0.9-23.5, p = 0.049). Cmax changed from 5.4 (95% CI 2.5-8.4) to 7.8 µg/mL (6.1-9.6), and systemic bioavailability was complete (102%) after the surgery. Overall, decreased paracetamol exposure in obesity, with recovery to normal drug levels (caplet) or even higher (syrup) post-LSG, was revealed. In conclusion, attention to paracetamol effectiveness/safety in obesity, and after bariatric surgery, is prudent.

Original languageEnglish
Article number1949
JournalJournal of Clinical Medicine
Volume8
Issue number11
DOIs
StatePublished - 12 Nov 2019

Keywords

  • Bariatric surgery
  • Drug absorption
  • Gastric emptying
  • Glucuronidation
  • Laparoscopic sleeve gastrectomy
  • Paracetamol (acetaminophen)

ASJC Scopus subject areas

  • Medicine (all)

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