An Allometric Model of Remifentanil Pharmacokinetics and Pharmacodynamics

Anesthesiology
Douglas J EleveldMichel M R F Struys

Abstract

Pharmacokinetic and pharmacodynamic models are used to predict and explore drug infusion schemes and their resulting concentration profiles for clinical application. Our aim was to develop a pharmacokinetic-pharmacodynamic model for remifentanil that is accurate in patients with a wide range of age and weight. Remifentanil pharmacokinetic data were obtained from three previously published studies of adults and children, one of which also contained pharmacodynamic data from adults. NONMEM was used to estimate allometrically scaled compartmental pharmacokinetic and pharmacodynamic models. Weight, age, height, sex, and body mass index were explored as covariates. Predictive performance was measured across young children, children, young adults, middle-aged, and elderly. Overall, 2,634 remifentanil arterial concentration and 3,989 spectral-edge frequency observations from 131 individuals (55 male, 76 female) were analyzed. Age range was 5 days to 85 yr, weight range was 2.5 to 106 kg, and height range was 49 to 193 cm. The final pharmacokinetic model uses age, weight, and sex as covariates. Parameter estimates for a 35-yr-old, 70-kg male (reference individual) are: V1, 5.81 l; V2, 8.82 l; V3, 5.03 l; CL, 2.58 l/min; Q2, 1.72 l/min;...Continue Reading

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Citations

May 17, 2017·Anesthesiology·Steven L Shafer, Dennis M Fisher
Jul 19, 2018·Clinical Pharmacokinetics·Marko M SahinovicAnthony R Absalom
Sep 4, 2018·British Journal of Clinical Pharmacology·Dagan O LonsdaleJoseph F Standing
Jul 11, 2019·Obesity Surgery·Georgia TsaousiVasilios Grosomanidis
Mar 10, 2020·Expert Opinion on Drug Metabolism & Toxicology·Brian J AndersonL Ignacio Cortinez
Mar 29, 2019·Anesthesiology·Brian J Anderson, Oliver Bagshaw
Jul 18, 2019·Anesthesiology·Michael C Montana
Jun 4, 2020·European Journal of Anaesthesiology·Benedikt PreckelJannicke Mellin-Olsen
Mar 15, 2019·Anesthesiology·Michael C MontanaEvan D Kharasch
Jun 13, 2020·Current Opinion in Anaesthesiology·Laura N HannivoortMichel M R F Struys
Aug 15, 2019·Experimental and Therapeutic Medicine·Yang ZhangNannan Ding
Oct 28, 2017·Paediatric Anaesthesia·Brian J Anderson, Nick Hg Holford
May 3, 2019·Current Opinion in Anaesthesiology·James D MorseBrian J Anderson
May 26, 2018·Current Opinion in Anaesthesiology·Luis I Cortínez, Brian J Anderson
Nov 1, 2020·Journal of Clinical Medicine·James D MorseBrian J Anderson
Jan 5, 2021·Anesthesiology·Douglas J Eleveld, Michel M R F Struys
Oct 15, 2020·Paediatric Anaesthesia·Anthony R AbsalomJ Robert Sneyd
Feb 17, 2021·Minerva anestesiologica·Marco Rossi, Fabio Sbaraglia
Apr 25, 2020·British Journal of Anaesthesia·Steven L Shafer
Jul 14, 2020·British Journal of Anaesthesia·Douglas J EleveldMichel M R F Struys
Oct 28, 2017·British Journal of Anaesthesia·K Kuck, T D Egan
Sep 21, 2020·British Journal of Anaesthesia·Talmage D EganThomas W Schnider

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