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.

Combination of gemcitabine and cisplatin in advanced non-small cell lung cancer.

A prospectively designed phase II study of non-small cell lung cancer stage IIIb and IV treated by gemcitabine and cisplatin was studied. The dosage of gemcitabine was 1 g/m2 weekly on day 1, 8 and 15. Cisplatin 100 mg/m2 was given on day 15 of each 28 day cycle. Twenty-eight patients were treated and all cases were evaluated for response. Survival and toxicity were determined in all enrolled patients. Thirteen (46.4%) achieved partial response (PR). By using Kaplan Meier's method the mean survival time was 19.8 months. One year survival was 66.6 per cent. Non hematologic toxicity consisted of mild nausea, vomiting, alopecia and hyperpigmentation of the skin. Rising creatinine of grade I was seen in 1.6 per cent. Anemia and leukopenia were common hematologic side effects with 27.5 per cent and 14.2 per cent of patients experiencing grade III and IV toxicity respectively. Both side effects were usually short lived and responsible for the delay of gemcitabine administration on day 8 and 15 in 18.3 per cent and 23.3 per cent on day 15 alone of chemotherapeutic courses respectively. We conclude that the combination of gemcitabine and cisplatin at this dosage achieved good response with moderate side effects.