Double-blind prospective randomized comparison of interferon gamma-1b versus placebo after autologous stem cell transplantation.

Thirty-eight patients, including 14 with Hodgkin's disease, 9 with non-Hodgkin's lymphomas, 4 with multiple myeloma and 11 with solid tumors, were enrolled in our study. Between March 1995 and March 1997, 24 of these patients had been autografted with peripheral blood, and 14 had received peripheral blood autografts plus bone marrow. The study was a double-blind, prospectively randomized comparison of interferon gamma-1b (IFN-gamma), given subcutaneously at a dose of 50 microg/m(2) daily for 30 days to 18 of the 38 patients, vs. placebo (20 of 38). Administration started after 2 consecutive days of >0.5 x 10(9) neutrophils/l following autologous stem cell transplantation. At a mean follow-up time of 536 +/- 269 days, disease-free survival (DFS) for the IFN-gamma and placebo groups was 728 vs. 510 days, respectively (p < 0.0750 by the Generalized Wilcoxon/Peto-Prentice test). Overall survival (OS) time for the IFN-gamma and placebo groups was 830 vs. 755 days, respectively. Despite the limited number of patients included in this comparison, a trend for superior DFS was observed in the IFN-gamma-treated group, a finding which merits further study.

Comparative bioavailability of two oral formulations of bromazepam in healthy volunteers.

The aim of this study was to assess the pharmacokinetic profile of two bromazepam (CAS 1812-30-2) formulations in 24 healthy volunteers. An open, randomised clinical trial designed as two-period crossover with 14-day washout between doses was employed. Plasma samples for assessments of their bromazepam concentration by HPLC-UV were obtained over 96 h after administration. No adverse effect was reported for any of the formulations administered. The following pharmacokinetics parameters were calculated: AUC(0-96 h), AUCinf, Cmax, Tmax, Ke and T1/2. The 90% confidence intervals (CI) for the mean test/reference individual ratios were 81-109 for AUC and 84-116 for Cmax. Since the 90% CI for both, AUC and Cmax ratios were within the 80-125% interval proposed by the Food and Drug Administration, it is concluded that the new bromazepam slow-release formulation is therapeutic equivalent to the conventional formulation for both, the extent and the rate of absorption after single dose administration in healthy volunteers.

Conversion and pharmacokinetic studies of a microemulsion formulation of cyclosporine in pediatric liver transplant patients.

A study of conversion from the standard cyclosporine treatment to a microemulsion formulation was performed in 29 stable pediatric liver transplant patients. The study was divided into conversion and in follow-up phases. While on therapy with the standard formulation at a mean daily dose+/-SD of 231+/-101.8 mg patients had a mean cyclosporine trough level of 188.7+/-51.4 ng/ml. Following a 1:1 conversion from the standard to the microemulsion formulation an increase in the cyclosporine trough level was observed in 75% of the patients. The mean cyclosporine trough level at this point was 221.5+/-69.7 ng/ml. On follow-up, the dose had to be reduced an average of 21.7% in 49% of the patients, whereas the rest remained stable. The incidence of adverse events was not significant and no differences were observed between the two formulations. The pharmacokinetic study of the microemulsion in 11 patients showed a monophasic curve, with an early absorption at 30 min and maximum concentration+/-SD of 880.8+/-72.8 ng/ml and time to maximum concentration of 1.5+/-0.12 hr. Basal time showed the least correlation with the area under the curve and T4 the most statistically significant. The microemulsion showed better bioavailability and pharmacokinetic characteristics than the standard formulation.