May 1976 874 The Journal of P E D I A T R I C S Pharmacokinetic analysis of the disposition intravenous theophylline in young children of The disposition of a single intravenous dose of theophylline, 3.2 mg/kg, was studied using a high-pressure liquid chromatographic assay in ten asthmatic children one to four years of age. The mean plasma theophylline clearance was 0.100 +_ 0.036 1/kg/hr, k~ 0.49 ++_ 0.30 hr L, Btt/z 3.38 +_ 1.11 ht; atV2 0.13 +_ 0.09 hr, and V1 0.25 + 0.13 1/kg. Plasma theophylline clearance was approximately 40% greater in these children than that reported in adults, mainly due to an increased rate of drug elimination. Large interindividual differences were observed. Analysis of data using either a two- or one-compartment model yielded almost idel~tical dosage regimens designed to rapidly achieve and maintain a chosen plasma theophylline concentration. Calculations based upon mean values of pharmacokinetie constants predict that a maintenance dose rate for aminophylfne of 30 mg/kg/day, after a loading dose of 5.6 mg/kg, would rapidly achieve and maintain a mean steady-state plasma concentration of theophylline of 10 mg/ l. Potential toxicity of such a regimen has not been excluded, since therapeutic trials (with achievement 'of steady state) have not yet been conducted. P. M. Loughnan, M.B.B.S., M.R.A.C.P.,* D. S. Sitar, Ph.D., R. I. Ogilvie, M.D., F.R.C.P.(C), A. Eisen, M.D., F.R.C.P.(C), Z. Fox, M.D., F.R.C.P.(C), and A. H. Neims, M.D., Ph.D., Montreal, P.Q., Canada RECENT DETAILED PHARMACOKINETIC STUDIES Of drug disposition in adults '- ~ have contributed to more rational drug administration. Without the use of multi- compartmental kinetic models, a significant errors can be From the Roche Developmental Pharmacology Unit, Department of Pharmacology and Therapeutics, McGill University," Department of Allergy and Clinical Immunology, Montreal Children's Hospital; and the Division of Clinical Pharmacology, Montreal General Hospital Supported in part by the Canadian Foundation for the Advancement of Therapeutics. Presented in part at the Annual Meeting of the Canadian Society for Clinical Investigation, Winnipeg, Manitoba, .lanua~y, 1975. *Holder of a Fellowship in Clinical Sciences (Clinical Pharmacology), National Health and Medical Research Council of A ustralia. Reprint address: Dr, P. M. Loughnan, Department of Pharmacology & Therapeutics, McIntyre Medical Sciences Bldg., Room 717, 3655 Drummond St., Montreal, Quebec H3G 1 Y6, Canada. introduced into calculations of loading and maintenance doses, and computation of an appropriate rate of infusion of the loading dose becomes impossible. Maintenance dose rates for most drugs in childhood often have been empirical, and of necessity derived from adult dosage as a proportional function of body weight or surface area. Too few correlations between rates of drug elimination and either body weight or surface area are available to enable confident extrapolation of pediatric dosage from adult See related article, p. 869. regimens. Interestingly, most reports do Support the suitability of. the surface area as a standard for the computation of a maintenance dose. Maintenance dose rates forcertain anticonvulsants in children4 do correlate with surface area, and toxicologic studies in animals5 reveal that rates of drug elimination relate better to body surface area than to body weight. Finally, although less definitive than clearance data, the plasma half-lives of certain agents, such as phenylbutazone and antipyrine,6 Vol. 88, No. 5, pp. 874-879