Covariates of tramadol disposition in the first months of life

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Presentation transcript:

Covariates of tramadol disposition in the first months of life K. Allegaert, J.N. van den Anker, J.N. de Hoon, R.H.N. van Schaik, A. Debeer, D. Tibboel, G. Naulaers, B.J. Anderson British Journal of Anaesthesia Volume 100, Issue 4, Pages 525-532 (April 2008) DOI: 10.1093/bja/aen019 Copyright © 2008 British Journal of Anaesthesia Terms and Conditions

Fig 1 The pharmacokinetic model. A two-compartment (central, peripheral) linear disposition model was used to fit the parent drug. An additional compartment for the M1 metabolite was linked to the central compartment by its formation clearance (CL2M1). M1 metabolite volume of distribution was fixed equivalent to the literature estimate of 224 litre 70 kg−1. Total body clearance of tramadol is the sum of CLother and CL2M1. CLM1 is the clearance of the M1 metabolite. British Journal of Anaesthesia 2008 100, 525-532DOI: (10.1093/bja/aen019) Copyright © 2008 British Journal of Anaesthesia Terms and Conditions

Fig 2 Quality of fit for parent tramadol in neonates over the study time (x-axes, h). The y-axes display the ratio of measured concentrations to those predicted from the pharmacokinetic analysis. (a) Values from the NONMEM post hoc step based on values of the parameters for the specific individual. (b) Values from the population parameters. British Journal of Anaesthesia 2008 100, 525-532DOI: (10.1093/bja/aen019) Copyright © 2008 British Journal of Anaesthesia Terms and Conditions

Fig 3 Quality of fit for M1 metabolite in neonates over the study time (x-axes, h). The y-axes display the ratio of measured concentrations to those predicted from the pharmacokinetic analysis. (a) Values from the NONMEM post hoc step based on values of the parameters for the specific individual. (b) Values from the population parameters. British Journal of Anaesthesia 2008 100, 525-532DOI: (10.1093/bja/aen019) Copyright © 2008 British Journal of Anaesthesia Terms and Conditions

Fig 4 M1 metabolite formation clearance increases with postmenstrual age. The population trend of M1 metabolic formation is highest in those neonates grouped as CYP3 (i.e. having a CYP2D6 activity score of 3) and is higher in neonates grouped as CYP2 compared with those grouped as CYP1 or CYP 0.5. British Journal of Anaesthesia 2008 100, 525-532DOI: (10.1093/bja/aen019) Copyright © 2008 British Journal of Anaesthesia Terms and Conditions