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Theophylline population pharmacokinetics from routine monitoring data in very premature infants with apnoea
Author(s) -
LEE T. C.,
CHARLES B. G.,
STEER P. A.,
FLENADY V. J.,
GRANT T. C.
Publication year - 1996
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1996.tb00182.x
Subject(s) - nonmem , medicine , theophylline , volume of distribution , population , pharmacokinetics , gestational age , dose , pediatrics , birth weight , apnea of prematurity , neonatology , anesthesia , pregnancy , environmental health , biology , genetics
1 Theophylline is commonly used in neonatology for the treatment and prophylaxis of apnoea of prematurity, and during ventilator weaning. 2 NONMEM was used to study the population pharmacokinetics of intravenous and oral theophylline from retrospective drug monitoring data in 82 premature neonates, weighing < 1500g at birth, and < 32 weeks gestational age. 3 Clearance (CL), volume of distribution ( V ) and oral bioavailability ( F 1) from liquid preparations were modelled alone, and under the influence of demographic and clinical covariates, assuming a 1‐compartment model with first‐order elimination. 4 The final population models with influential co‐variates were as follows: CL (1h ‐1 ) = 0.0000123 *body weight (g) + 0.000377 *postnatal age (days); V (1) = 0.000937 *body weight (g); F = 0.918. 5 The CL was lower and V was higher than previously reported for less premature neonates, term babies, and older children. 6 Predictive performance of the population models was evaluated by Bayesian forecasting in a similar, but independent cohort of 30 infants. There was statistically insignificant bias and imprecision between measured and predicted serum theophylline concentrations. 7 Based on the validated population models, recommended maintenance theophylline dosages are provided for infants aged between 2 and 50 days, and weighing 700 to 2000 g.