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Population pharmacokinetics of intravenous caffeine in neonates with apnea of prematurity
Author(s) -
Lee Toong Chow,
Charles Bruce,
Steer Peter,
Flenady Vicki,
Shearman Andrew
Publication year - 1997
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/s0009-9236(97)90097-7
Subject(s) - medicine , nonmem , volume of distribution , gestational age , apnea of prematurity , pharmacokinetics , population , caffeine , apnea , anesthesia , birth weight , pregnancy , biology , environmental health , genetics
Objective To study the population pharmacokinetics of caffeine after intravenous administration to premature infants with apnea. Methods A prospective, blinded parallel study in which daily caffeine citrate doses of 30, 15, and 3 mg/kg were administered over 7 days by intermittent intravenous infusion. Arterial blood samples (three to six per patient) were assayed for caffeine content by means of HPLC. Population pharmacokinetic modeling was performed with NONMEM. Results Clearance (L/hr) = (0.399 · current weight [grams]) + (0.000128 · postnatal age [days]). For gestational age >28 weeks, volume of distribution (L) = (0.000764 · weight [grams]) + (0.0468 · postnatal age [days]); for gestational age ≤28 weeks, volume of distribution (L) = (0.000755 · weight [grams]) + (0.0224 · postnatal age [days]). Interpatient variability (coefficient of variation, in percent) was ~25% for clearance and ~11% for volume of distribution. Intrapatient error (standard deviation) was 3.9 mg/L. There was insignificant bias between observed and model‐predicted serum caffeine concentrations in a separate group of 30 infants. Conclusions Caffeine was well tolerated at all doses. Clearance was markedly lower and volume of distribution was higher than the values reported previously for term infants and adults. Both parameters were significantly influenced by postnatal age and current body weight, whereas volume of distribution in infants >28 weeks gestational age was higher than that in more premature babies. The predictive performance and the clinical application of the derived population models was satisfactorily shown. Clinical Pharmacology & Therapeutics (1997) 61 , 628–640; doi: