Summary
Theophylline pharmacokinetics were studied in 12 infants (age 3 weeks–6.5 months) with bronchiolitis. 9 of the 12 patients received a single dose of aminophylline (5.0–8.5 mg/kg) whereas the remainder were at steady-state receiving multiple doses (2.5–5.0 mg/kg) of aminophylline. The dose was administered IV over 0.5–1.0 h. An HPLC method was used to measure theophylline concentrations in serum and urine. Peak serum concentrations of theophylline measured by HPLC ranged from 8.48–21.6 µg/ml. Total, renal and nonrenal clearance of theophylline ranged from 4.66 to 19.25, 1.07 to 5.76 and 3.59 to 16.83 ml/min/m2, respectively. Mean apparent volume of distribution and elimination half-life were 8.75 l/m2 and 11.38 h, respectively. Although no significant correlation was observed between age and theophylline kinetic parameters, clearance appeared to increase and half-life decrease with age. Our patients had a substantially lower clearance and longer half-life as compared to published data in children >1 year of age. A five-fold variation in theophylline clearance demonstrates the need for monitoring theophylline serum concentration to minimize the risk of potential toxicity.
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References
Aranda JV, Sitar DS, Parsons WD, Loughnan PM, Neims AH (1976) Pharmacokinetic aspects of theophylline in premature newborns. N Engl J Med 295: 413–416
Benati M, Latini R, Marra G, Assael BM, Parini AR (1981) Theophylline metabolism during the first month of life and development. Pediatr Res 15: 304–308
Brazier JL, Renaud H, Ribon B, Salle BL (1979) Plasma anthine levels in low birth weight infants treated with theophylline. Arch Dis Child 54: 194–199
Brodie B, Axelrod J, Reichenthal J (1952) Metabolism of theophylline (1, 3-dimethylxanthine) in man. J Biol Chem 194: 215–222
Chang KC, Lauer DA, Bell TD, Chai H (1978) Altered theophylline pharmacokinetics during acute respiratory viral illness. Lancet 1: 1132–3
Eisen AH, Bacal HL (1963) The relationship of acute bronchiolitis to bronchial asthma-a 4 to 14 year follow-up. Pediatrics 31: 859–861
Ellis EF, Kaysooko R, Levy G (1976) Pharmacokinetics of theophylline in children with asthma. Pediatrics 58: 542–547
Foucard T, Berg T, Johennson SGO, Warren B (1971) Virus serology and serum IgE levels in children with asthmatoid bronchitis. Acta Pediatr Scand 60: 621–629
Giacoia G, Jusko WJ, Menke J, Koup JR (1976) Theophylline pharmacokinetics in premature infants with apnea. J Pediatr 89: 829–832
Gibaldi M, Perrier D (eds) (1975) Pharmacokinetics. Marcel Dekker, New York, pp 11–17
Henderson FW, Clyde WA Jr, Collier AM (1979) The etiologic and epidemiologic spectrum of bronchiolitis in pediatric practice. J Pediatr 95: 183–191
Kadlec GJ, Ha LT, Jarboe CH, Richards D, Karibo JM (1978) Theophylline half-life in infants and young children. Ann Allergy 40: 303–310
King DM, Heeley AF, Kuzemko JA (1979) Half-life of theophylline in the preterm baby with apneic attacks. Arch Dis Child 54: 238–239
Latini R, Assael BM, Bonati M, Caccamo ML, Gerna M, Mandelli M, Marini A, Sereni F, Tognoni G (1978) Kinetics and efficacy of theophylline in the treatment of apnea in the premature newborn. Eur J Clin Pharmacol 13: 203–207
Loughnan RM, Sitar DS, Olgilvie RI, Eisen A, Fox A, Neims AH (1975) Pharmacokinetic analysis of the disposition of intravenous theophylline in young children. J Pediatr 88: 874–879
Lenney W, Milner AD (1978) Alpha and beta adrenergic stimulants in bronchiolitis and wheezy bronchitis in children under 18 months of age. Arch Dis Child 53: 707–709
Levy G, Koysooko R (1976) Renal clearance of theophylline in man. J Clin Pharmacol 16: 329–332
Nassif EG, Weinberger MM, Shaunon D, Guiang SF, Hendeles L, Jimenez D, Ekwo E (1981) Theophylline disposition in infancy. J Pediatr 98: 158–161
Orcutt JJ, Kozak PP Jr, Gillman SA, Cimmins LH (1977) Microscale method for theophylline in body fluids by reversed-phase, high pressure liquid chromatography. Clin Chem 23: 599–601
Renton K (1978) Theophylline pharmacokinetics in respiratory viral illness (C). Lancet 2: 160–161
Rooney JC, Williams HE (1971) The relationship between proved viral bronchiolitis and subsequent wheezing. J Pediatr 79: 744–747
Rosen JP, Danish M, Ragni MD, Saccar CL, Yaffe SJ, Lecks HI (1979) Theophylline pharmacokinetics in the young infant. Pediatrics 64: 248–251
Rutter N, Milner AD, Hiller EJ (1975) Effect of bronchodilators on respiratory resistance in infants and young children with bronchiolitis and wheezy bronchitis. Arch Dis Child 50: 719–722
Simons FER, Friesen FR, Simons KJ (1980) Theophylline toxicity in term infants. Am J Dis Child 134: 39–41
Simons FER, Simons KJ (1978) Pharmacokinetics of theophylline in infancy. J Clin Pharmacol 18: 472–476
Stempel DA, Clyde WA Jr, Henderson FJ, Collier AM (1980) Serum IgE levels and the clinical expression of respiratory illness. J Pediatr 97: 185–190
Wohl MEB (1977) Bronchiolitis. In: Kendig EL, Chernick V (eds) Disorders of the respiratory tract in children. WB Saunders, Philadelphia
Wohl ME, Chernick V (1978) Bronchiolitis. Am Rev Respir Dis 118: 759–81
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Franko, T.G., Powell, D.A. & Nahata, M.C. Pharmacokinetics of theophylline in infants with bronchiolitis. Eur J Clin Pharmacol 23, 123–127 (1982). https://doi.org/10.1007/BF00545965
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DOI: https://doi.org/10.1007/BF00545965