We randomly assigned 20 patients with progressively worsening generalized myasthenia gravis of recent onset whose illness was not controlled by anticholinesterase therapy to treatment with either cyclosporine (6 mg per kilogram of body weight per day) or placebo. Patients who had been treated with thymectomy, steroids, or other immunosuppressive agents were excluded. The duration of treatment was 12 months. Disease activity was assessed by quantified strength testing and by measurements of antihuman acetylcholine-receptor antibody. Patients were assessed at 6 months and 12 months, or at the following early end points: drug failure (doubling of creatinine), treatment failure (respiratory or swallowing difficulty), or protocol violation (stopping medication for more than five days). At six months, patients in the cyclosporine group had had significantly more objective improvement in strength; one early end point had been reached (drug failure; no treatment failures). In the placebo group, three early end points had been reached (all treatment failures). The decline in titers of acetylcholine-receptor antibody was larger in the treated group, although the difference was not statistically significant. At the end of the study (after 12 months of treatment or arrival at an earlier end point), improvement in strength and reduction in titers of anti-receptor antibody continued to be greater in the cyclosporine group. Nephrotoxicity occurred in three patients receiving cyclosporine but was nonprogressive with a reduction in dosage and reversible with discontinuation of the drug. These results are preliminary and need confirmation, but we conclude that cyclosporine is probably an effective therapy in some patients with myasthenia gravis.

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Summary: Purpose:A new capsule dosage form of carbamazepine (CBZ) has been developed, consisting of three different types of beads (immediate-release, extended-release, and enteric-release) that may be taken sprinkled on food or swallowed for easy administration. We compared the pharmacokinetics of the extended-release dosage form of CBZ (Carbatrol capsules) twice daily with the conventional immediate-release formulation of CBZ four times daily.Methods: The randomized, double-blind, two-way, crossover study was conducted at two sites, with a planned sample size of 24 adult patients with epilepsy. Each treatment was administered for 2 weeks. At the end of the 2-week period, blood samples were obtained hourly for a 24-h period.Results: The 90% confidence intervals (CI) of the ratio of the means of the extended-release formulation twice daily to the immediate-release formulation four times daily were within the range of 0.80-1.25 for each of the pharmacokinetic parameters for CBZ and for the summation of CBZ and CBZ-epoxide (CBZ-E). There was no difference in the frequency of seizures between treatment (p = 0.103).Conclusions: Our results demonstrate that extended-release CBZ twice daily was bioequivalent to immediate-release CBZ four times daily, with regard to CBZ levels and summation of CBZ and CBZ-E levels, based on the pharmacokinetic parameters evaluated. Substituting one formulation for the other did not cause patients to have a significant change in seizure frequency. Key Words: Carbamazepine-PharmacokineticsExtended release-Epilepsy.Since its first introduction into clinical use for the treatment of epilepsy in the 1970s (1-3), carbamazepine (CBZ) has become a drug of choice for the treatment of simple partial, complex partial, and secondarily generalized tonic-clonic seizures (SPS, CPS, SGTCS). The conventional immediate-release forms of CBZ, require frequent (three or four times daily) dosing, however, and variability in CBZ drug levels in the blood has been reported. Both of these issues are problematic (4-6).Adherence to a medication regimen is a major issue in the pharmacological treatment of epilepsy, with studies frequently linking seizures to poor adherence. Adherence can be affected by both the frequency of drug administration as well as the occurrence of side effects, frequently linked to blood levels of drug. Additional factors affecting adherence to a regimen by patients with epilepsy may be memory difficulties and frequent seizures. In studies from several centers, adherence to antiepileptic drug (AED) dosing regimens ranged from 39 to 82% (7)(8)(9)(10)(11). In a study of patients with epilepsy using electronic compliance monitors, adherence to a once-or twice-daily regimen was -80%, as contrasted with -40% adherence to a four-times-daily regimen (12). A patient's variable adherence to an AED regimen can lead to increased variability in blood levels (1 3). One of the issues involved in the dosing of CBZ is its high degree of insolubility and variations in bioavailability. Peak-to-trough fluctu...