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

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.

Optimized In Silico Modeling of Drug Absorption after Gastric Bypass: The Case of Metformin

“…Since it is unknown to what extent these adaptations occur, it is difficult and non-ideal to change these values. Moreover, only some drugs [66][67][68] may show higher exposure after bariatric surgery, as metformin does [69], while for others, oral absorption may be impaired after surgery [70][71][72].…”

Managing the Unpredictable: Mechanistic Analysis and Clinical Recommendations for Lamotrigine Treatment after Bariatric Surgery

“…One of the least discussed complications of bariatric surgery involves altered oral drug absorption and bioavailability, potentially leading to efficacy/safety issues of various orally administered medications [ 3 , 4 ]. A few bariatric procedures are commonly available worldwide, including sleeve gastrectomy, some variations of gastric bypass surgeries, notably Roux-en-Y gastric bypass (RYGB) and the newer one-anastomosis gastric bypass (OAGB), and more; and while each procedure is unique in the gastrointestinal anatomic changes that it brings and despite the fact that literature data is mainly available on RYGB, all of these procedures may affect oral drug pharmacokinetics [ 5 , 6 , 7 , 8 , 9 ], with clinically significant ramifications. Until recently, the literature in this field was mainly limited to case reports and small studies.…”

The Effects of Bariatric Surgery and Gastrectomy on the Absorption of Drugs, Vitamins, and Mineral Elements

“…Figure 4 shows the methods of reconstruction of the gastrointestinal tract after proximal gastrectomy. Various forms of gastrectomy may significantly change the pharmacokinetics of orally taken drugs [17]. The lack of stomach results in mechanometabolic and deficiency metabolic disorders.…”