Morphine Glucuronidation and Elimination in Intensive Care Patients: A Comparison with Healthy Volunteers

Anesthesia and Analgesia
Sabine J G M AhlersCatherijne A J Knibbe

Abstract

Although morphine is used frequently to treat pain in the intensive care unit, its pharmacokinetics has not been adequately quantified in critically ill patients. We evaluated the glucuronidation and elimination clearance of morphine in intensive care patients compared with healthy volunteers based on the morphine and morphine-3-glucuronide (M3G) concentrations. A population pharmacokinetic model with covariate analysis was developed with the nonlinear mixed-effects modeling software (NONMEM 7.3). The analysis included 3012 morphine and M3G concentrations from 135 intensive care patients (117 cardiothoracic surgery patients and 18 critically ill patients), who received continuous morphine infusions adapted to individual pain levels, and 622 morphine and M3G concentrations from a previously published study of 20 healthy volunteers, who received an IV bolus of morphine followed by a 1-hour infusion. For morphine, a 3-compartment model best described the data, whereas for M3G, a 1-compartment model fits best. In intensive care patients with a normal creatinine concentration, a decrease of 76% was estimated in M3G clearance compared with healthy subjects, conditional on the M3G volume of distribution being the same in intensive car...Continue Reading

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Citations

Jun 9, 2016·Expert Review of Clinical Pharmacology·Janneke M BrusseeCatherijne A J Knibbe
Oct 28, 2016·Expert Review of Clinical Pharmacology·Manuel A BaarslagDick Tibboel
May 17, 2017·Clinical Pharmacokinetics·Sjoerd de HoogdCatherijne A J Knibbe
Sep 2, 2017·Pediatric Critical Care Medicine : a Journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies·John N van den AnkerDick Tibboel
Jul 26, 2017·Pain Practice : the Official Journal of World Institute of Pain·Sjoerd de HoogdCatherijne A J Knibbe
May 8, 2018·Clinical Pharmacokinetics·Anne van RongenCatherijne A J Knibbe
Aug 12, 2016·Pediatric Critical Care Medicine : a Journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies·Abraham J ValkenburgCormac V Breatnach
Nov 21, 2020·The Journal of Pediatric Pharmacology and Therapeutics : JPPT : the Official Journal of PPAG·Kanecia O ZimmermanKevin M Watt

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