An integrated population pharmacokinetic meta-analysis of propofol in morbidly obese and nonobese adults, adolescents, and children

J Diepstraten, V Chidambaran, S Sadhasivam, H J Blussé van Oud-Alblas, T Inge, B van Ramshorst, E P A van Dongen, A A Vinks, C A J Knibbe, J Diepstraten, V Chidambaran, S Sadhasivam, H J Blussé van Oud-Alblas, T Inge, B van Ramshorst, E P A van Dongen, A A Vinks, C A J Knibbe

Abstract

This study describes a population pharmacokinetic meta-analysis of propofol to characterize the influence of body size measures and age in morbidly obese and nonobese adults, adolescents, and children. Sixty morbidly obese and nonobese adult patients (55-167 kg; 21-79 years) and 34 morbidly obese and nonobese adolescents and children (37-184 kg; 9-20 years) were included. The results show that clearance increased with total body weight in an allometric function while age was found to influence clearance in a bilinear fashion with two distinct slopes, reflecting an initial increase and subsequent decrease as a result of aging. Using these two functions, the influence of both (over)weight and age on propofol clearance was well characterized, which may provide a basis for dosing across this diverse group of patients.CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e73; doi:10.1038/psp.2013.47; advance online publication 11 September 2013.

Figures

Figure 1
Figure 1
Individual post hoc propofol clearance estimates vs. total body weight for the simple model (model A) and three covariate pharmacokinetic models (B, C, and D) for morbidly obese adults (black circles), adolescents and children (gray circles) and their nonobese controls (n = 94). In model B, the black line indicates the population clearance values for both the adult and adolescent population; in model C, the black line indicates the population clearance values for adults and the gray line the population clearance values for adolescents; and in model D, the black dotted lines indicate the population clearance values for 15, 41, and 65 years.
Figure 2
Figure 2
Interindividual variability of propofol clearance vs. age for the simple model without covariates (model A) and the final covariate model including age and total body weight on propofol clearance (model E).
Figure 3
Figure 3
Observed vs. population-predicted ln propofol concentrations of the final model (model E). Panels represent data of morbidly obese adults, nonobese adults, morbidly obese children and adolescents, and nonobese children and adolescents. The solid gray line represents the line of identity, x = y.
Figure 4
Figure 4
Model-based predictions of population clearance estimates of propofol vs. age for patients with different total body weights.

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