Pharmacokinetics of Paracetamol before and after Roux-en-Y gastric bypass

The number of bariatric procedures performed in The Netherlands is increasing, especially Roux-en-Y gastric bypass (RYGB). Little is known about the effect of RYGB on the pharmacokinetics of drugs, neither the surgery procedure itself nor the loss of weight in the long term. It is unclear how to dose drugs both shortly and long after the surgery. Paracetamol (PCM) is a widely used analgesic used by patients because of RYGB, but it can also be used for pother reasons. PCM is a potential hepatotoxic drug when used in too high dosages.

Morbid obesity, RYGB surgery and the normalization of weight affect the pharmacokinetics of PCM, including both absorption and elimination, as well as the formation of toxic metabolites. A higher dosage of PCM could be considered to overcome the lower maximal concentration (Cmax) and total exposure (AUC), but this option may be limited by the additional formation of toxic metabolites. This is why all these aspects will be combined in this research to understand the pharmacokinetics of PCM before and after RYGB surgery.

The objective of this study is to assess the effect of a RYGB on the pharmacokinetics of a single dose of 1000 mg PCM before the surgery, within one month after the surgery and 6 months after the surgery.

This study is an open-label, longitudinal pharmaceokintics study. 20 morbidly obese patients will be included, who are planned to undergo a Roux-en-Y gastric bypass surgery. Furthermoe, 8 healthy non-obese volunteers will be included to assess the pharmacoekintics of a single oral dose of 1000 mg PCM.

RYGB affects pharmacokinetics of PCM within one month and after 6 months after the surgery.

Study planned on 1 February 2020

Single oral dose of PCM 1000 mg