Theophylline disposition in adolescents with asthma.
Adolescents frequently require medication for acute and chronic illnesses. A proper dosage schedule is needed to achieve efficacy without toxicity during adolescence when there are marked changes in body size and organ function. Theophylline disposition was studied in 70 asthmatic adolescents, ages 8-18 years, to determine if pubertal changes in body size, composition, and organ function are associated with changes in drug disposition. Forty-eight youngsters were studied as outpatients and 22 while hospitalized. Half-life (t1/2) was computed for all patients. Volume of distribution and clearance were determined for inpatients only. Chronological age and anthropometric growth parameters were measured. Lean body mass (LBM) was derived from anthropometric measurements. Half-life was significantly correlated with developmental stage (Tanner r = 0.42, age r = 0.33, p less than 0.01), and body size (height r = 0.39, LBM r = 0.33, weight r = 0.33, p less than 0.01). LBM (kg/kg) was significantly correlated with volume of distribution (L/kg) (r = 0.59, p less than 0.01). Best-fits for t1/2 contained two variables: t1/2 = -4.57 + 1.31 (sex) + 0.0687 (height) (r = 0.48) and t1/2 = -3.54 + 1.32 (sex) + 0.0725 (LBM) (r = 0.43). Chronological age alone is not a useful basis for determining medication dosages due to the heterogeneity in rates of development and body size among adolescents. Half-life increases with increasing height or LBM. Although compliance is clearly an important factor in achieving optimal control of symptoms, this study demonstrates that dose adjustment during times of rapid growth during puberty is equally important.
Cary
J
J
Department of Pediatrics, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY 10467-2490.
Hein
K
K
Dell
R
R
D000293:Adolescent; D000553:Ambulatory Care; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism*; D015992:Body Mass Index; D002648:Child; D004334:Drug Administration Schedule; D005260:Female; D006207:Half-Life; D006760:Hospitalization; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D011627:Puberty / Q000378:metabolism; D013806:Theophylline / Q000008:administration & dosage / Q000493:pharmacokinetics*
D013806:Theophylline