J H Botha1, M J du Preez, R Miller, M Adhikari. 1. Department of Experimental and Clinical Pharmacology, Medical School, Congella, Republic of South Africa. botha@med.und.ac.za
Abstract
OBJECTIVE: The population pharmacokinetics of amikacin, in neonates, was investigated using the nonlinear mixed effects model (NONMEM). METHODS: One hundred and six steady-state amikacin serum levels were obtained from 53 black neonates with a mean gestational age of 35.1 weeks and mean age at the start of treatment of 3.1 days. A one-compartment model was used to fit the data. RESULTS: The final models for clearance (CL) and volume of distribution (V) were: CL(l.h(-1)) = 0.031WT(1.45) x P and V(l) = 0.316WT(1.44) where WT = birth weight (kg) and P = 1.28 for girls and 1.0 for boys. Inclusion of other fixed effect parameters in the model did not significantly improve the fit of the data. The inter-individual variability for CL and V were 18% and 13%. respectively. Intra-individual variability was 29%. Mean (95% CI) values of CL, V and half-life were 0.048 (0.045, 0.051) l.h(-1).kg(-1), 0.434 (0.414, 0.453) l.kg(-1) and 6.4 (6.2, 6.6) h respectively. CONCLUSION: Birth weight was an important determinant of both CL and V and, in this data set, gender was also found to influence CL. Mean population pharmacokinetic values were within the range of those previously derived for other neonatal populations using traditional methods.
OBJECTIVE: The population pharmacokinetics of amikacin, in neonates, was investigated using the nonlinear mixed effects model (NONMEM). METHODS: One hundred and six steady-state amikacin serum levels were obtained from 53 black neonates with a mean gestational age of 35.1 weeks and mean age at the start of treatment of 3.1 days. A one-compartment model was used to fit the data. RESULTS: The final models for clearance (CL) and volume of distribution (V) were: CL(l.h(-1)) = 0.031WT(1.45) x P and V(l) = 0.316WT(1.44) where WT = birth weight (kg) and P = 1.28 for girls and 1.0 for boys. Inclusion of other fixed effect parameters in the model did not significantly improve the fit of the data. The inter-individual variability for CL and V were 18% and 13%. respectively. Intra-individual variability was 29%. Mean (95% CI) values of CL, V and half-life were 0.048 (0.045, 0.051) l.h(-1).kg(-1), 0.434 (0.414, 0.453) l.kg(-1) and 6.4 (6.2, 6.6) h respectively. CONCLUSION: Birth weight was an important determinant of both CL and V and, in this data set, gender was also found to influence CL. Mean population pharmacokinetic values were within the range of those previously derived for other neonatal populations using traditional methods.
Authors: Catherine M T Sherwin; Sofia Svahn; Antje Van der Linden; Roland S Broadbent; Natalie J Medlicott; David M Reith Journal: Eur J Clin Pharmacol Date: 2009-03-21 Impact factor: 2.953
Authors: Gudrun Würthwein; Andreas H Groll; Georg Hempel; Felice C Adler-Shohet; Jay M Lieberman; Thomas J Walsh Journal: Antimicrob Agents Chemother Date: 2005-12 Impact factor: 5.191
Authors: Julie Autmizguine; Daniel K Benjamin; P Brian Smith; Mario Sampson; Philippe Ovetchkine; Michael Cohen-Wolkowiez; Kevin M Watt Journal: Curr Clin Pharmacol Date: 2014
Authors: Sílvia M Illamola; Hoa Q Huynh; Xiaoxi Liu; Zubin N Bhakta; Catherine M Sherwin; Theodore G Liou; Holly Carveth; David C Young Journal: Antimicrob Agents Chemother Date: 2018-09-24 Impact factor: 5.191
Authors: Michiel F Schreuder; Abraham J Wilhelm; Arend Bökenkamp; Simone M H Timmermans; Henriette A Delemarre-van de Waal; Joanna A E van Wijk Journal: Clin J Am Soc Nephrol Date: 2009-08-27 Impact factor: 8.237