These studies document the ability to use oral administration of tributyrin to achieve pharmacologically relevant concentrations of butyrate in rodent plasma. They also document the nonlinear nature of butyrate clearance. These data are being used in the design of clinical trials of oral tributyrin in patients with malignancies and hemoglobinopathies.

Because 4-aminopyridine (AP) improves residual deficits in some multiple sclerosis (MS) patients but has a narrow toxic-to-therapeutic margin, we compared the safety and efficacy of two target peak serum concentration ranges (low: 30 to 59 ng/ml and high: 60 to 100 ng/ml). We enrolled eight MS patients with temperature-sensitive visual and motor deficits in a randomized, placebo-controlled, double-blind, crossover trial of short-term oral AP treatment. We randomized patients to a sequence of three treatments on three separate days: placebo, low serum concentration, and high serum concentration. We determined dosing to achieve the desired steady-state peak serum concentration ranges from a test dose and population pharmacokinetic parameters using bayesian estimation. Contrast sensitivity, standard neurologic examination, ratings of videotaped neurologic examinations, and quantitative strength assessment all improved with treatment, but flicker fusion frequency, visual evoked response latencies, and Expanded Disability Status Scale scores did not. All patients experienced side effects during the high-serum-concentration arm. A grand mal seizure occurred at a serum AP level of 104 ng/ml, and an acute confusional episode occurred at 114 ng/ml. AP treatment produced improvements in residual deficits in MS patients, but the occurrence of significant toxicity suggests that AP serum levels should be monitored and peak levels above 100 ng/ml should be avoided. Concentration-control methodology may be useful in testing putative treatments for other neurologic diseases.

No abstract

We evaluated the absolute bioavailability of ciprofloxacin, a new quinoline carboxylic acid, in 12 healthy male volunteers. Doses of 200 mg were given to each of the volunteers in a randomized, crossover manner 1 week apart orally and as a 10-min intravenous infusion. Ciprofloxacin is a new quinoline carboxylic acid with a broad spectrum of activity encompassing the Enterobacteriaceae, Pseudomonas aeruginosa, and Staphylococcus aureus (methicillin susceptible and resistant) (2). Ciprofloxacin has both oral and parehteral dosing forms (4, 5), possibly allowing initial parenteral therapy for serious infections followed by oral therapy, thereby simplifying care and decreasing costs. We evaluated the pharmacokinetics of the oral and intravenous forms of ciprofloxacin, as well as the extent and reliability of absorption. Other investigators have addressed this to some extent but have used a microbiologic assay for their determination of drug concentration in serum (6). Consequently, we undertook a randomized, crossover design evaluation of the bioavailability of ciprofloxacin in 12 healthy volunteers. MATERIALS AND METHODSStudy design. Twelve nonobese healthy males between 21 and 29 years of age were randomly assigned to receive 200 mg of ciprofloxacin either intravenously as a 10-min infusion in 200 ml of normal saline or orally as two 100-mg tablets after an overnight fast. In the subsequent week, volunteers were crossed over to the alternate regimen. No Drug assay. Ciprofloxacin concentration was measured in serum and urine by high-pressure liquid chromatography, a variant of the assay of Gau et al. (3). The serum assay used protein precipitation, reverse-phase high-pressure liquid chromatography, and fluorometric detection. The urine assay used sample dilution followed by direct injection. Quinine was used as an internal standard. A Waters C18 ,uBondapak reverse-phase column was used for the assay. The mobile phase consisted of 27% methanol, 0.8% tetrahydrofuran, and 0.067 M phosphate buffer (pH 3.0). A flow rate of 1.3 ml/min was used. The column was heated to 500C.The assays were determined to be linear between 0.01 and 1 ,ug/ml for serum and between 0.025 and 1.5 pg/ml for urine. The sensitivities of the assays were at least 0.01 p.g/ml.