4-Aminopyridine in multiple sclerosis: prolonged administration.

In an earlier study, we demonstrated efficacy of single oral doses of 4-aminopyridine (4-AP) in improving motor and visual signs in multiple sclerosis (MS) patients for a mean of 4.97 hours. We attempted to determine whether efficacy could safely be prolonged using multiple daily doses over several days by administering 7.5 to 52.5 mg 4-AP to 17 temperature-sensitive MS patients in one to three daily doses at 3- to 4-hour intervals over 1 to 5 days in a double-blind study. Nine of these patients were also tested with identically appearing placebo. Thirteen of the 17 patients (76%) given 4-AP showed clinically important motor and visual improvements compared with three of nine in the placebo group. Average peak improvement scores were 0.40 for 4-AP and 0.12 for placebo. Seventy percent of the daily 4-AP improvements lasted 7 to 10 hours. The improvements for two consecutive doses of 4-AP lasted a mean of 7.07 hours (83% of the average 8.53-hour treatment-observation period) compared with 2.36 hours for placebo (26% of the average 9.06-hour treatment-observation period). No serious side effects occurred. 4-AP is a promising drug for the symptomatic treatment of MS.

Single-dose study of the effect of terfenadine on theophylline absorption and disposition.

Terfenadine, a nonsedating antihistamine, and theophylline, a methylxanthine used extensively in the treatment of asthma, have potential for frequent concomitant administration. A single-dose pharmacokinetic study was performed to investigate the potential for a drug-drug interaction affecting serum theophylline concentrations. No statistically significant effect on theophylline absorption or elimination was found when 60 mg of terfenadine was concomitantly administered with 4 mg/kg of theophylline in 17 normal healthy male volunteers. The results of this single-dose study suggest there is no significant acute pharmacokinetic interaction affecting serum theophylline concentrations when terfenadine and theophylline are administered concomitantly as single isolated doses. Further investigation is needed to determine if repeated administration of terfenadine is equally without effect on theophylline absorption or disposition.

Pharmacokinetic evaluation of the terfenadine-theophylline interaction.

Based on results of studies of a possible terfenadine-theophylline interaction on file with Merrell Dow, Inc., a randomized, crossover study was undertaken to determine if there were a pharmacokinetic interaction between these two medications. Seventeen normal volunteers were randomized to receive theophylline or a theophylline-terfenadine combination for 14 days, followed by a 2-week washout period, with crossover to the other treatment for 14 days. Serum theophylline concentrations were measured on the last day of each treatment phase for determination of pharmacokinetic parameters. No differences were found in elimination rate constant, elimination half-life, area under the concentration-time curve, time to peak concentration, or maximum theophylline concentration. It is concluded that concomitant terfenadine therapy does not affect the pharmacokinetic profile of theophylline in healthy male volunteers.

Pentamidine therapy in renal failure: case report and literature review.

The literature lacks adequate dosing guidelines for modifying pentamidine therapy in renal failure. This report describes a patient in renal failure undergoing intermittent peritoneal dialysis who is treated with pentamidine for Pneumocystis carinii pneumonia. Data on pentamidine's disposition are reviewed.