Apparent decrease in population clearance of theophylline: Implications for dosage

• Published in: Clinical pharmacology and therapeutics Vol. 62; no. 5; pp. 483 - 489
• Main Authors: Asmus, Michael J., Weinberger, Miles M., Milavetz, Gary, Marshik, Patricia, Teresi, Mary E., Hendeles, Leslie
• Format: Journal Article
• Language: English
• Published: New York, NY Nature Publishing 01-11-1997
• Subjects: Adolescent; Age Factors; Asthma - blood; Asthma - drug therapy; Biological and medical sciences; Body Weight; Bronchodilator Agents - administration & dosage; Bronchodilator Agents - blood; Bronchodilator Agents - pharmacokinetics; Child; Child, Preschool; Chronic Disease; Drug Administration Schedule; Humans; Infant; Medical sciences; Pharmacology. Drug treatments; Respiratory system; Theophylline - administration & dosage; Theophylline - blood; Theophylline - pharmacokinetics; Human; Dosage adjustment; Respiratory disease; Toxicity; Bronchodilator; Elimination; Variations; Antiasthma agent; Asthma; Chemotherapy; Treatment; Cohort study; Secondary effect; Xanthine derivatives; Obstructive pulmonary disease; Effective dose; Pharmacokinetics; Theophylline
• ISSN: 0009-9236; 1532-6535
• DOI: 10.1016/S0009-9236(97)90043-6

Background
Having observed in recent years that the theophylline dose requirements needed to attain peak serum concentrations of 10 to 20 μg/ml infrequently reached previously described mean values, we hypothesized that a downward shift in the range of dose requirements had occurred among patients with asthma.
Study design
We examined dosage requirements needed to attain peak serum concentrations of 10 to 20 μg/ml in all patients with chronic asthma treated with theophylline by the Pediatric Allergy and Pulmonary Clinic at the University of Iowa from 1990 to 1994 (n = 300) and at the Pediatric Pulmonary Clinic at the University of Florida from 1992 to 1995 (n = 93). We then compared these doses to previous dose requirements from 1978 to 1983 determined in the same manner.
Results
Despite similar mean peak serum concentrations during both time periods (14 μg/ml), mean theophylline dosage requirements during the period of this study were approximately 25% lower among all age groups than those previously observed (p < 0.001). There were no significant differences in mean dosage requirements between the Iowa and Florida patients in any age group examined.
Conclusions
Theophylline dose requirements needed to attain serum concentrations of 10 to 20 μg/ml have decreased significantly from those on which current dosing recommendations are based. This suggests a decrease in mean clearance of the population.
Clinical Pharmacology & Therapeutics (1997) 62, 483–489; doi: