An open-trial evaluation of mitoxantrone in the treatment of progressive MS.

We treated 13 patients with progressive MS with mitoxantrone. All patients received a standard IV dose of mitoxantrone (8 mg/m2) every 3 weeks for a total of seven infusions, with dosage adjustments depending on the hematologic profile at the nadir. The treatment was well tolerated, with the most common side effect being mild nausea. Four of seven women developed transient secondary amenorrhea. The postenrollment clinical behavior of these patients was generally more favorable than during the 18 months prior to enrollment (only three of 13 patients developed an increase in the Expanded Disability Status Scale of more than 0.5 points), suggesting a possible treatment effect, but comparison with two historical control groups (both the active and placebo groups from the Canadian Cooperative Trial of Cyclophosphamide and Plasma Exchange) does not suggest that mitoxantrone was efficacious. Eight of 12 patients had evidence of MRI activity on 13 of 29 follow-up visits. This small, open-labeled pilot study did not provide strong support for proceeding with a randomized, controlled trial of this dosage regimen of mitoxantrone in patients with progressive MS.

The pharmacokinetics of flurbiprofen in younger and elderly patients with rheumatoid arthritis.

The pharmacokinetics of flurbiprofen (Ansaid Tablets, Upjohn Company of Canada, Don Mills, Ontario) were evaluated in both younger (40 to 60 years) and elderly (65 to 83 years) rheumatoid arthritic patients after both a 100-mg single-dose administration and at steady state during a 100-mg twice-a-day dosage regimen. Both flurbiprofen plasma concentration-time profiles and the urinary excretion of flurbiprofen and its major metabolites were evaluated. The results indicate that the pharmacokinetics of flurbiprofen are linear in both age groups based on only minor changes between single-dose and steady-state parameter determinations and the agreement between calculated and predicted accumulation values in plasma concentrations. Only minor differences in the pharmacokinetic parameters were observed between the younger and elderly patients. Only free flurbiprofen clearance was found to have a significant but variable correlation to patient age. The effect of flurbiprofen on the urinary excretion of two prostaglandins were also evaluated throughout this study. In both age groups, the maximum decrease in urinary excretion was observed after the first dose, and this effect was maintained throughout the remainder of the study. Percent decreases from baseline in urinary excretion during drug administration were similar for both age groups. Similar side-effect profiles were observed between age groups.