Comparative steady-state bioavailability of sustained-release theophylline preparations: Theo-Dur, Uni-Dur and Xanthium.
Steady-state bioavailability of sustained-release theophylline (SRT); Theo-Dur, Uni-Dur and Xanthium were compared in 10 healthy males with theophylline clearance ranged from 0.3 - 0.8 ml/min/kg. Each of 400-mg SRT was administered once daily before breakfast for 7 consecutive days, one-week washout period in a crossover fashion. Serial blood samples were collected over 24 hours on days 6 and 7. Serum theophylline concentrations were determined by fluorescence polarized immunoassay. We found that the oral bloavailability relative to Franol (%F [90% CI]) of Theo-Dur, Uni-Dur and Xanthium were 97 (93-106), 85 (79-96) and 77 (72-87), respectively. Average bioequivalence revealed that the Css(min) (microg/ml) of Uni-Dur (5.07) was higher than Theo-Dur (4.29), and Xanthiume (4.18), while the Css(max) and Css(av) (microg/ml) of Theo-Dur (11.02, 7.87) were statistically higher than Uni-Dur (8.51, 6.91) and Xanthium (7.65, 6.27). The extent of absorption assessed by AUCss(0.24) of Theo-Dur was significantly greater than Uni-Dur and Xanthium. However, fluctuation index (% FI) of Theo-Dur (232) was twofold higher than Uni-Dur (137) and Xanthium (113). The median Tss(max) of Uni-Dur was 12 hours which was significantly longer than Xanthium (7 hours) and Theo-Dur (8 hours). There were no statistically significant differences between Uni-Dur and Xanthium regarding bioavailability, Css(max), Css(av) as well as % FI. Moreover, 400 mg OD of Uni-Dur and Xanthium are suitable for subjects with a theophylline clearance of 0.3-0.55 ml/min/kg while 400 mg OD Theo-Dur can be used in subjects with slower clearance rates of 0.3-0.39 ml/min/kg. Subjects with rapid theophylline clearance rates of 0.65-0.8 ml/min/kg required a higher dose of theophylline and twice-daily dosing was more appropriate.
Rojanasthien
N
N
Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Thailand.
Kovjiriyapan
K
K
Manorot
M
M
Pothirat
C
C
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000188:drug therapy; D001682:Biological Availability; D001993:Bronchodilator Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008168:Lung / Q000098:blood supply / Q000187:drug effects / Q000502:physiology; D008297:Male; D013785:Thailand; D013806:Theophylline / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use
D001993:Bronchodilator Agents; D003692:Delayed-Action Preparations; D013806:Theophylline