Therapeutic equivalence of a generic slow-release theophylline tablet.
OBJECTIVE
To evaluate the relative bioavailability and clinical efficacy of two slow-release theophylline products.


METHODS
Randomized, double-blind, crossover trial.


METHODS
A university-affiliated clinical research center.


METHODS
Fourteen adults with asthma.


METHODS
The patients received a generic slow-release theophylline tablet or Theo-Dur at bedtime for 5 nights.


RESULTS
Serum drug concentrations were measured after the last dose. Attenuation of exercise-induced bronchospasm (EIB) was included as a surrogate for efficacy. There was no significant difference in extent of absorption. The mean differences between the generic product and Theo-Dur in area under the curve was -13.9 micrograms/ml.hr-1 (95% CI -41 to 12.9, p = 0.3) and in peak concentration (Cmax), -0.5 microgram/ml (95% CI -1.7 to 2.7, p = 0.6). In contrast, the generic product was absorbed more rapidly; the mean differences in the time to peak concentration (Tmax) was -3.0 hours (95% CI -4.3 to -1.7, p = 0.0003), in trough concentration (Cmin), -0.9 microgram/ml (95% CI -1.9 to -0.01, p = 0.05), and in fluctuation between Cmax and Cmin, +128% (95% CI 40 to 217, p = 0.008). Neither product effectively attenuated EIB, since mean serum concentrations during the exercise challenges were unexpectedly below 10 micrograms/ml after both products.


CONCLUSIONS
These two products are not bioequivalent, but the difference in absorption rates is unlikely to be clinically important in most patients (i.e., they are therapeutic equivalents).
Hendeles
L
L
College of Pharmacy, Department of Pediatrics, University of Florida, Gainesville, USA.
Breton
A L
AL
Beaty
R
R
Harman
E
E
D000042:Absorption; D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D001250:Asthma, Exercise-Induced / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D001682:Biological Availability; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D016568:Drugs, Generic / Q000493:pharmacokinetics*; D005080:Exercise Test; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008875:Middle Aged; D013607:Tablets; D013806:Theophylline / Q000493:pharmacokinetics*; D013810:Therapeutic Equivalency
D003692:Delayed-Action Preparations; D016568:Drugs, Generic; D013607:Tablets; D013806:Theophylline