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

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 µg·h/mL with AUC_0-t difference of 9.5 µg·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 µg/mL (3.6-4.8) after LSG (p = 0.032). In the syrup groups, AUC_0-t increased from 13.4 to 25.6 µg·h/mL, with AUC_0-t difference of 12.2 µg·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 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.