Slow release theophylline disposition and effect in elderly patients with chronic obstructive lung disease: influence of dose formulation and institutionalization.
We studied the steady-state disposition of slow release theophylline tablets and granules in 12 institutionalized (I) and 12 community-dwelling (C) elderly patients with fixed chronic obstructive lung disease. Design was open label with random order crossover; each formulation was given 5 min before food every 12 h for 7 days. Age (median 70 y, range 55-88), sex, smoking status, and baseline lung function off drug were similar. Though plasma concentration (Cp) was higher with the tablets as was the area under the Cp vs time curve: 134 (74-252) vs 121 (75-197) mg h l-1; p = 0.028. The standard deviation of Cp over one dose interval was lower with the granules. FEV 1.0 was slightly improved over baseline. Dose required to reach target Cp was higher in the institutionalized group (12.6 vs 8.6 mg kg-1 day-1; p = 0.003) as was apparent clearance; I:94 (43-148) ml hr-1 kg-1 vs C:68 (34-163); p = 0.003. Although bioavailability was slightly reduced for the granules, fluctuations of Cp was less, and we failed to find a food effect that was clinically important in geriatric subjects.
Montgomery
P R
PR
Department of Pharmacology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Aoki
F Y
FY
Mitenko
P A
PA
Vanzieleghem
M
M
Sitar
D S
DS
D000368:Aged; D003692:Delayed-Action Preparations; D005260:Female; D005541:Forced Expiratory Volume; D006760:Hospitalization; D006801:Humans; D008173:Lung Diseases, Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010366:Peak Expiratory Flow Rate; D013806:Theophylline / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D014797:Vital Capacity
D003692:Delayed-Action Preparations; D013806:Theophylline