European Journal of Clinical Pharmacology

, Volume 24, Issue 3, pp 371–374 | Cite as

Plasma theophylline and caffeine and plasma clearance of theophylline during theophylline treatment in the first year of life

  • G. Lönnerholm
  • B. Lindström
  • L. Paalzow
  • G. Sedin


Plasma concentrations of caffeine and theophylline were simultaneously determined in 17 preterm infants after oral administration of aminophylline for treatment of apnoea. The ratio of caffeine/theophylline concentration in plasma increased during the first 2 weeks of treatment, owing to the longer time required for caffeine than for theophylline to reach steady state. The caffeine/theophylline ratio at steady state was 0.57±0.03 (mean±SE). Thus, caffeine contributed significantly to the total methylxanthine load in the infants. The plasma clearance of theophylline was calculated from the plasma steady state concentrations. In 3 preterm infants treated with oral aminophylline, repeated sampling showed an approximately linear increase in clearance with time from 16.8±0.4 (mean±SE) at a postnatal age of 6–11 days to 30.9±2.5 ml/kg/h at 64–69 days. In 1 full-term infant treated with oral theophylline from 3.5 to 11.5 months of age, the plasma clearance of theophylline increased in a roughly linear manner, reaching a plateau of about 100 ml/kg/h at 6–7 months of age. This corresponds to the clearance found in 1–4 year old infants.

Key words

theophylline caffeine apnoea aminophylline infant plasma level plasma clearance 


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  1. Aldridge A, Aranda JV, Neims AH (1979) Caffeine metabolism in the newborn. Clin Pharmacol Ther 25: 447–453Google Scholar
  2. Aranda JV, Sitar DS, Parsons W, Loughnan PM, Neims AH (1976) Pharmacokinetic aspects of theophylline in premature newborns. N Engl J Med 295: 413–416Google Scholar
  3. Aranda JV, Turmen T (1979) Methylxanthines in apnoea of prematurity. Clin Perinatol 6: 87–108Google Scholar
  4. Aranda JV, Cook CE, Gorman W, Collinge JM, Loughnan PM, Outerbridge EW, Aldridge A, Neims AH (1979) Pharmacokinetic profile of caffeine in the premature newborn with apnoea. J Pediatr 94: 663–668Google Scholar
  5. Bory C, Baltassat P, Porthault M, Bethenod M, Frederich A, Aranda JV (1978) Biotransformation of theophylline to caffeine in premature newborn. Lancet 2: 1204–1205Google Scholar
  6. Bory C, Baltassat P, Porthault M, Bethenod M, Frederich A, Aranda JV (1979) Metabolism of theophylline to caffeine in premature newborn infants. J Pediatr 94: 988–993Google Scholar
  7. Brazier J-L, Renaud H, Ribou B, Salle BL (1979) Plasma xanthine levels in low birthweight infants treated or not treated with theophylline. Arch Dis Child 54: 194–199Google Scholar
  8. Cottancin G, Baltassat P, Bory C, Challamel M-J, Frederich A (1977) Pharmacocinétique de la théophylline chez le noveauné de petit poids de naissance. Pédiatrie 32: 677–684Google Scholar
  9. Floberg S, Lindström B, Lönnerholm G (1980) Simultaneous determination of theophylline and caffeine after extractive alkylation in small volumes of plasma by gas chromatography — mass spectrometry. J Chromatogr 221: 166–169Google Scholar
  10. Giacoia G, Jusko WJ, Menke J. Koup JR (1976) Theophylline pharmacokinetics in premature infants with apnoea. J Pediatr 89: 829–832Google Scholar
  11. Kuzemko JA, Paala J (1973) Apnoeic attacks in the newborn treated with aminophylline. Arch Dis Child 48: 404–406Google Scholar
  12. Loughnan PM, Sitar DS, Ogilvie RI, Eisen A, Fox Z, Neims AH (1976) Pharmacokinetic analysis of the disposition of intravenous theophylline in young children. J Pediatr 88: 874–879Google Scholar
  13. Ogilvie RI (1978) Clinical pharmacokinetics of theophylline. Clin Pharmacokinet 3: 267–293Google Scholar
  14. Peabody J, Neese AL, Lucey JG, Philip AGS, Soyka LF (1977) Decreased hypoxic, hyperoxic and bradycardic episodes as responses of neonates to theophylline. Pediatr Res 11: 419Google Scholar
  15. Shannon DC, Gotay F, Stein IM, Rogers MC, Todres ID, Moglan FMB (1975) Prevention of apnoea and bradycardia in low-birth-weight infants. Pediatrics 55: 589–594Google Scholar
  16. Soyka LF, Neese AL (1978) Perinatal exposure to methylxanthines: Possible effects on pregnancy outcome. Clin Pharmacol Ther 23: 130Google Scholar
  17. Takieddine FN, Tserng K-Y, King KC, Kalhan SC (1981) Postnatal development of theophylline metabolism in preterm infants. Semin Perionatol 5: 351–358Google Scholar
  18. Turmen T, Davis J, Aranda JV (1981) Relationship of dose and plasma concentration of caffeine and ventilation in neonatal apnoea. Semin Perinatol 5: 326–331Google Scholar
  19. Uauy R, Shapiro D, Smith B, Warshaw J (1975) Effect of theophylline on severe primary apnoea of prematurity. A preliminary report. Pediatrics 55: 595–598Google Scholar

Copyright information

© Springer-Verlag 1983

Authors and Affiliations

  • G. Lönnerholm
    • 1
  • B. Lindström
    • 2
  • L. Paalzow
    • 3
  • G. Sedin
    • 1
  1. 1.Department of PediatricsUniversity HospitalUppsalaSweden
  2. 2.Department of DrugsNational Board of Health and WelfareUppsalaSweden
  3. 3.Department of BiopharmacyUniversity of UppsalaUppsalaSweden

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