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Open AccessArticle

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

1
Department of Clinical Pharmacology, School of Pharmacy, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel
2
Clinical Pharmacy, Herzliya Medical Center, Herzliya 46140, Israel
3
Department of Surgery B, Soroka University Medical Center, Beer Sheva 84101, Israel
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2019, 8(11), 1949; https://doi.org/10.3390/jcm8111949
Received: 24 September 2019 / Revised: 3 November 2019 / Accepted: 8 November 2019 / Published: 12 November 2019
(This article belongs to the Section Pharmacology)
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. View Full-Text
Keywords: paracetamol (acetaminophen); bariatric surgery; laparoscopic sleeve gastrectomy; drug absorption; glucuronidation; gastric emptying paracetamol (acetaminophen); bariatric surgery; laparoscopic sleeve gastrectomy; drug absorption; glucuronidation; gastric emptying
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Porat, D.; Markovic, M.; Zur, M.; Fine-Shamir, N.; Azran, C.; Shaked, G.; Czeiger, D.; Vaynshtein, J.; Replyanski, I.; Sebbag, G.; Dahan, A. Increased Paracetamol Bioavailability after Sleeve Gastrectomy: A Crossover Pre- vs. Post-Operative Clinical Trial. J. Clin. Med. 2019, 8, 1949.

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