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.

Bioequivalence study of generic atenolol tablets in healthy Thai volunteers.

Two preparations of 50 mg and 100 mg atenolol tablets were evaluated for their bioequivalence in twelve healthy Thai subjects (Prenolol, Berlin Pharmaceutical Industry, as the test formulations vs Tenormin, Zeneca Limited, as the reference formulations). A single oral dose of each preparation was administered in a randomized two-way crossover design, starting from either 50 mg of Prenolol vs Tenormin, thereafter, either 100 mg of Prenolol vs Tenormin. The washout period between each treatment was one week. Atenolol plasma concentrations were determined by the HPLC technique with fluorometric detection. Pharmacokinetic parameters were analyzed by the noncompartmental pharmacokinetic method using TOPFIT. The means and parametric 90 per cent confidence intervals of the ratio [Prenolol/Tenormin] of AUC0-infinity and Cmax were 1.16 (1.05-1.27) and 1.23 (1.07-1.38) for 50 mg preparations and 1.10 (1.00-1.20) and 1.13 (0.95-1.31) for 100 mg preparations, respectively. These values were well within the acceptable bioequivalence ranges. The mean differences of Tmax [Prenolol-Tenormin] were less than 20 per cent for both 50 mg and 100 mg preparations. Hence, Prenolol and Tenormin were bioequivalent with respect to the rate and extent of absorption.

Pharmacokinetics and bioavailability studies of generic ondansetron, and the innovator preparation, in healthy Thai male volunteers.

The pharmacokinetics and bioequivalence of two oral formulations of ondansetron were evaluated; Zetron (Biolab Pharmaceutical, Bangkok, Thailand), as the test formulation and Zofran (Glaxo Wellcome Operations, Greenford, UK), as the reference formulation. The two products were administered as a single oral dose of 8 mg according to a randomized two-way crossover design to 12 healthy Thai male volunteers. The washout period between treatment was 1 week. Ondansetron plasma concentrations were measured using HPLC. The oral bioavailability of ondansetron averaged 67 per cent and the elimination half-life after oral administration was 5.6 hours. The means and parametric 90 per cent CI of the ratios of Cmax and AUC 0-alpha [mu Zetron (Test)/mu Zofran (Reference)] were 0.95 (0.84-1.07) and 0.94 (0.80-1.10), respectively. These values were well within the bioequivalence range of 0.8-1.25 as established by the US-FDA. The mean difference of Tmax (Test-Reference) was approximately 20 per cent. Thus, our study demonstrated bioequivalence of the two products (Zetron and Zofran) regarding the rate and extent of absorption.

A case of hypomagnesemia hypocalcemia as a complication of aminoglycoside and review of the literature.

A 28-year-old woman was admitted to the ENT Department of the Faculty of Medicine, Chiang Mai University because of left otitis externa, chronic mastoiditis and facial nerve palsy (lower motor neurone). Left radical mastoidectomy with wide debridement of granulation and necrotic tissue at ear canal, dura, sigmoid sinus, ossicle and facial nerve were done two weeks after admission. Multiple pus culture from the lesion revealed different types of organisms e.g. proteus mirabilis, beta strep non group A, and enterococci beta type. Several aminoglycosides were alternately given for two months without improvement of ear infection. She developed carpopedal spasm with hypocalcemia after three weeks of such treatment. Hypomagnesemia was recognized. Calcium and milk supplement gave temporary relief, but permanent relief was obtained after aminoglycoside was discontinued. Serum electrolyte had reversed to normal on follow-up.