Caffeine Pharmacokinetics In a Pediatric Population
A.C.Falcao(1,2), M.M.Fernandez de Gatta, M.F.Delgado Iribarnegaray, D.Santos Buelga, M.J.Garcia, A.Dominguez-Gil, J.M.Lanao
Department of Pharmacy and Pharmaceutical Technology. Faculty of Pharmacy. University of Salamanca. Salamanca.Spain (1) Laboratory of Pharmacology. Faculty of Pharmacy. University of Coimbra. Coimbra. Portugal (2)Supported by Junta Nacional de Investigacao Cientifica e Tecnologica (JNICT) Portugal
Neonatal apnea is a common problem: it occurs in 25% of infants under 2500 gr and 80% of infants under 1000 gr. Methylxanthines (caffeine and theophylline) are widely, used for the treatment of this condition.
Clinical pharmacokinetic (PK) data from premature neonates receiving caffeine were collected and analyzed using NONMEM, a computer program designed for population PK analysis. A total of 145 measured serum caffeine concentrations were obtained from 75 hospitalized patients. There were 34 female and 41 male neonates with a birth weight ranged from 0.6 to 2.0 kg, gestational ages ranged from 23.71 to 32.00 weeks and postnatal ages at last caffeine serum level ranged from 2 to 102 days.
The pharmacokinetic model used was a one-compartment open model with either zero-order infusion or first-order absorption and first-order elimination. The effect of a variety of developmental, demographic and clinical factors (sex, birth weight, actual weight, gestational age, postnatal age, postconceptional age, phenobarbital and parenteral nutrition) on clearance (CL) and volume of distribution (V) was investigated. Hypothesis testing to evaluate potentially significant factors produced a final model in which clearance was based on weight (kg) raised to an exponential power and postnatal age (weeks). Volume of distribution in this population was adequately described using a linear relationship with the weight. Estimates of the coefficients of the regression formulas, the intra and inter-individual errors, and their 95% confidence intervals will be provided.
In conclusion, the identification of several patient factors and the quantification of their influence on caffeine disposition can be used to individualize the therapy. In this study a mean of only 2 serum levels per patient were utilized to provide information which should prove useful in the design and adjustment of caffeine dosage schedules in premature neonates with apnea of prematurity.