Am J Perinatol 2007; 24(1): 039-047
DOI: 10.1055/s-2006-958163
Copyright © 2007 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Serum Caffeine Concentrations in Preterm Neonates

Alonso E. Concha Leon1 , Kelly Michienzi2 , Chang-Xing Ma3 , Alastair A. Hutchison1
  • 1Department of Pediatrics, University at Buffalo, State University of New York, Buffalo, New York
  • 2Department of Pharmacy, The Women and Children's Hospital of Buffalo, Kaleida Health, Buffalo, New York
  • 3Department of Biostatistics, University at Buffalo, State University of New York, Buffalo, New York
Further Information

Publication History

Publication Date:
27 December 2006 (online)

ABSTRACT

Caffeine therapy reduces apnea of prematurity, promotes successful extubation from invasive positive-pressure ventilation, and decreases the incidence of bronchopulmonary dysplasia. The recommended dosing for caffeine is a loading dose of 20 mg/kg followed by a 5 mg/kg/d maintenance dose. However, controversy exists about the optimal dosing regimen and data on serum caffeine concentrations in extremely immature infants are scant. We determined serum caffeine concentrations ~7 days after starting therapy with a 20 or 25 mg/kg loading dose and a 6 mg/kg/d maintenance dose in 154 infants with a mean gestational age of 29 weeks. The 25th to 75th percentile range for the serum caffeine concentrations with the two dosing regimens was equivalent, ~18 to 23 mg/L. Within the first 14 postnatal days, the serum caffeine concentrations were not dependent on postmenstrual age, weight, or postnatal age, and were in a range that is safe and therapeutic. This latter observation remained valid over the ranges of clinical and laboratory assessments of renal and hepatic functions that are usually found in practice. Routine measurement of steady-state serum caffeine concentrations in infants 24 to 35 weeks gestational age is not required in the absence of ongoing apnea/hypopnea or signs compatible with toxicity.

REFERENCES

  • 1 Erenberg A, Leff R, Haack D et al.. Caffeine citrate for the treatment of apnea of prematurity: a double-blind, placebo-controlled study.  Pharmacotherapy. 2000;  20 644-652
  • 2 Gunn T R, Metrakos K, Riley P, Willis D, Aranda J V. Sequelae of caffeine treatment in preterm infants with apnea.  J Pediatr. 1979;  94 106-109
  • 3 Henderson-Smart D, Davis P. Prophylactic methylxanthines for extubation in preterm infants.  Cochrane Database Syst Rev. 2003;  (1) CD000139
  • 4 Schmidt B, Roberts R, Davis P et al.. Caffeine therapy for apnea of prematurity.  N Engl J Med. 2006;  354 2112-2121
  • 5 Steer P, Flenady V, Shearman A et al.. High dose caffeine for extubation of preterm infants.  Arch Dis Child Fetal Neonatal Ed. 2004;  89 F499-F503
  • 6 Aranda J V, Cook C E, Gorman W et al.. Pharmacokinetic profile of caffeine in the premature newborn infant with apnea.  J Pediatr. 1979;  94 663-668
  • 7 Roberts R J. Methyl xanthine therapy. In: Roberts RJ Drug Therapy in Infants. Philadelphia, PA; W.B. Saunders 1984: 119-137
  • 8 Le Guennec J C, Billon B, Pare C. Maturational changes of caffeine concentrations and disposition in infancy during maintenance therapy for apnea of prematurity: influence of gestational age, hepatic disease and breast-feeding.  Pediatrics. 1985;  76 834-840
  • 9 Pons G, Carrier O, Richard M et al.. Developmental changes of caffeine elimination in infancy.  Dev Pharmacol Ther. 1988;  11 258-264
  • 10 Romagnoli C, Carolis M D, Muzii U et al.. Effectiveness and side effects of two different doses of caffeine in preventing apnea in premature infants.  Ther Drug Monit. 1992;  14 14-19
  • 11 Thomson A H, Kerr S, Wright S. Population pharmacokinetics of caffeine in neonates and young infants.  Ther Drug Monit. 1996;  18 245-253
  • 12 Lee T C, Charles B, Steer P, Flenady V, Shearman A. Population pharmacokinetics of intravenous caffeine in neonates with apnea of prematurity.  Clin Pharmacol Ther. 1997;  61 628-641
  • 13 Scanlon J E, Chin K C, Morgan M E, Durbin G M, Hale K A, Brown S S. Caffeine or theophylline for neonatal apnoea?.  Arch Dis Child. 1992;  67 425-428
  • 14 Comer A M, Perry C M, Figgitt D P. Caffeine citrate: a review of its use in apneoa of prematurity.  Paediatr Drugs. 2001;  3 61-79
  • 15 al-Alaiyan S, al-Rawithi S, Raines D et al.. Caffeine metabolism in premature infants.  J Clin Pharmacol. 2001;  41 620-627
  • 16 Giacoia G P, Jungbluth G L, Jusko W J. Effect of formula feeding on oral absorption of caffeine in premature infants.  Dev Pharmacol Ther. 1989;  12 205-210
  • 17 Gorodischer R, Karplus M. Pharmacokinetic aspects of caffeine in premature infants with apnoea.  Eur J Clin Pharmacol. 1982;  22 47-52
  • 18 Finer N N, Higgins R, Kattwinkel J, Martin R J. Summary proceedings from the apnea-of-prematurity group.  Pediatrics. 2006;  117(3 Pt 2) S47-S51
  • 19 Carrier O, Pons G, Rey E et al.. Maturation of caffeine metabolic pathways in infancy.  Clin Pharmacol Ther. 1988;  44 145-151
  • 20 Pesce A J, Rashkin M, Kotagal U. Standards of laboratory practice: theophylline and caffeine monitoring.  Clin Chem. 1998;  44 1124-1128

Alastair A HutchisonM.B.Ch.B. F.R.A.C.P. 

Division of Neonatology, Department of Pediatrics, The Women and Children's Hospital of Buffalo

219 Bryant Street, Buffalo, NY 14222-2006

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