Increased Paracetamol Bioavailability after Sleeve Gastrectomy: A Crossover Pre- vs. Post-Operative Clinical Trial.
JOURNAL OF CLINICAL MEDICINE(2019)
摘要
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 AUC(0-t) increased from 9.1 to 18.6 mu g.h/mL with AUC(0-t) difference of 9.5 mu g.h/mL (95% CI 4.6-14.5, p = 0.003). C-max increased from 1.8 (95% CI 1.2-2.5) to 4.2 mu g/mL (3.6-4.8) after LSG (p = 0.032). In the syrup groups, AUC(0-t) increased from 13.4 to 25.6 mu g.h/mL, with AUC(0-t) difference of 12.2 mu g.h/mL (95% CI 0.9-23.5, p = 0.049). C-max changed from 5.4 (95% CI 2.5-8.4) to 7.8 mu g/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.
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关键词
paracetamol (acetaminophen),bariatric surgery,laparoscopic sleeve gastrectomy,drug absorption,glucuronidation,gastric emptying
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