Pharmacokinetics and Pharmacodynamics of Intravenous Paracetamol in Morbidly Obese and Non- Obese Patients.
NCT Number: NCT06549062
Status: RECRUITING
Study Type: OBSERVATIONAL
Conditions: Acetaminophen Toxicity|Obesity, Morbid
Sponsor: University Hospital, Ghent
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 70
Study Design: Observational Model: |Time Perspective: p
Start Date: 2020-09-11
Completion Date: 2025-01-01
Locations: University Hospital, Ghent, Oost-Vlaanderen, 9000, Belgium

Summary:
Obese patients may need higher doses of acetaminophen (APAP) for adequate analgesia, due to increased total clearance and distribution volume. APAP-induced hepatotoxicity is mainly caused through CYP2E1 pathway. Its activity is induced by obesity, potentially endangering the safety profile of APAP. Metabolic-dysfunction associated liver disease (MASLD) is an important associated risk factor for APAP induced-hepatotoxicity.

The primary endpoint of this study is to validate Van Rongen's prediction model on plasma concentration of paracetamol and its metabolites and extend it to the steady state phase over a period of 30 hours by measuring plasma concentrations of paracetamol and its metabolites and comparing them with the plasma concentrations predicted by the model by Van Rongen et al.

In addition, results obtained from venous blood will be compared with results obtained via VAMS after finger stick. If VAMS correlates well with plasma concentrations of paracetamol and its NAPQI adducts, future interventional studies may utilize the patient-friendly VAMS technology in an effort to further investigate the safety and efficacy of higher doses of paracetamol in obese patients and possibly other patient groups.

The secondary endpoints of this study are liver function tests before and after 30hrs of paracetamol administration, the VAS pain scores, the surgical pleth index (SPI) and the consumption of piritramide as recorded by a PCIA pump.

Primary Outcome Measures: acetaminophen, plasma concentrations and capillary blood concentrations, first six hours after IV administration of the loading dose of 2g|acetaminophen, plasma concentrations and capillary blood concentrations, the six hours after IV administration of the fifth dose of 1g acetaminophen|acetaminophen-glucuronide metabolite, plasma concentrations and capillary blood concentrations, the first six hours after IV administration of a loading dose of 2g acetaminophen|acetaminophen-glucuronide metabolite, plasma concentrations and capillary blood concentrations, the first six hours after IV administration of fifth dose of 1 g acetaminophen|acetaminophen-sulphate metabolite, plasma concentrations and capillary blood concentrations, the first six hours after IV administration of 2g IV acetaminophen|acetaminophen-sulphate metabolite, plasma concentrations and capillary blood concentrations, the six hours after IV administration of fifth dose of 1g IV acetaminophen|acetaminophen- Cysteine protein adduct, plasma concentrations and capillary blood concentrations, the first six hours after IV administration of 2 g loading dose of acetaminophen|acetaminophen- Cysteine protein adduct, plasma concentrations and capillary blood concentrations, the six hours after IV administration of the fifth dose of 1g acetaminophen|acetaminophen- mercapturate protein adduct, plasma concentrations and capillary blood concentrations, the first six hours after IV administration loading dose 2g acetaminophen|acetaminophen- mercapturate protein adduct, plasma concentrations and capillary blood concentrations, the six hours after IV administration of the fifth dose of 1g acetaminophen
Secondary Outcome Measures: pain score using Visual analog scale at rest, patient indicates the pain score on a visual analog scale ranging from 0-100mm, hours after starting acetaminophen: 3,4,5,6, 24, 24:15, 25:30,27,30|pain score using Visual analog scale after movement, patient indicates the pain score on a visual analog scale ranging from 0-100mm, hours after starting acetaminophen: 3,4,5,6, 24, 24:15, 25:30,27,30|surgical pleth index (SPI) at rest, non invasive measurement of the balance between nociception and antinociception ranging from 0-100., hours after starting acetaminophen: 3,4,5,6, 24, 24:15, 25:30,27,30|surgical pleth index (SPI) after movement, non invasive measurement of the balance between nociception and antinociception ranging from 0-100., hours after starting acetaminophen: 3,4,5,6, 24, 24:15, 25:30,27,30|patient controlled intravenous analgesia: piritramide consumption, piritramide consumption as a measure of the quality of pain relief with acetaminophen and ibuprofen., first 30 hours after starting acetaminophen or until discharge from the hospital