Bioequivalence of immediate-release theophylline capsules.
A three-way crossover study in 18 healthy male volunteers was conducted to evaluate the bioequivalence of three different 200 mg anhydrous theophylline immediate-release (IR) capsules. The products had not been rated as therapeutically equivalent by the US Food and Drug Administration (FDA) owing to a lack of bioequivalence data. Serum samples were obtained from 0 to 34 h after dosing. Mean time of maximum serum concentration (T(max)) ranged from 1.3 to 1.4 h. Mean values for the maximum serum concentration (C(max)) and the area under the serum concentration-time curves (AUC) differed by <5% for the three products. The confidence limits for Ln-transformed C(max) and AUC ranged from >/=89 to </=113%. It was concluded that the three products were bioequivalent. In addition, the rapid in vitro dissolution of these formulations, as well as the reported high solubility and high permeability of theophylline, was predictive of the lack of any bioavailability differences among the three products.
Meyer
M C
MC
Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee, Memphis, TN 38163, USA. mmeyer@utmem.edu
Jarvi
E J
EJ
Straughn
A B
AB
Pelsor
F R
FR
Williams
R L
RL
Shah
V P
VP
D000328:Adult; D019540:Area Under Curve; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002214:Capsules; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D006207:Half-Life; D006801:Humans; D008297:Male; D012995:Solubility; D013806:Theophylline / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013810:Therapeutic Equivalency
D001993:Bronchodilator Agents; D002214:Capsules; D013806:Theophylline