Search

The aim of this study, directed toward the low-temperature preservation of dog small intestine, was to determine the most satisfactory conditions of use of the cryophylactic agent dimethylsulfoxide (DMSO). Earlier preservation experiments performed on isolated intestinal loops have shown that after rewarming and extraction of this cryophylactic substance by perfusion, an important edema had taken place. This led us to investigate the conditions of its appearance and to search for means to suppress or reduce it. Using a technique similar to that described by Cady et al. (5) in their study of dog kidney glycerolization, the experimental principle of which consists in observing variations in weight of the organ as a function of time and various perfusion methods, the following results have been obtained: 1. 1. The origin of the edema is of an osmotic nature and it appears principally during the extraction phase of the cryophylactic agent. 2. 2. The magnitude of the edema is a function of the concentration of DMSO in the impregnation perfusate, and of the duration of the impregnation phase. 3. 3. The effectiveness of the substance under study, at least in regard to the edema, is improved when: (a) DMSO is used at a relatively low concentration (about 10% vv); (b) tissue impregnation time of the cryophylactic agent is short (

AIMS: The pharmacokinetics and dose proportionality of rizatriptan single oral doses from 2.5 to 15 mg administered as solutions to healthy volunteers were studied. METHODS: In a randomized, crossover study with four periods, twenty-four healthy volunteers (12 males and 12 females) took single oral doses of 2.5, 5, 10, and 15 mg rizatriptan in Periods 1-4. In a fifth period, subjects received 4 mg intravenous (i.v.) rizatriptan as a reference. Plasma and urine rizatriptan concentrations were determined at several timepoints/intervals for 12 and 24 h, respectively. RESULTS: The arithmetic mean AUC values following single oral doses of 2.5, 5, 10, and 15-mg rizatriptan were 16, 33, 72, and 127 ng ml-1 h, respectively, in males; and 19, 42, 97, and 161 ng ml-1 h, respectively, in females. The overall bioavailability (F ) of rizatriptan was approximately 40% in males. Following the 4 mg reference i.v. dose, the apparent plasma clearance (CL) and renal clearance (CLr ) were 1042 and 225 ml min-1, respectively, in males; and 821 and 174 ml min-1, respectively, in females. CONCLUSIONS: The disposition kinetics of oral rizatriptan were linear for doses of 2. 5-10 mg in males, and for doses of 2.5-5 mg in females. However, the degree of nonlinearity for higher doses was minor for both genders. The plasma concentrations of rizatriptan were slightly greater in women compared to men but the difference was not considered to be clinically meaningful. Also, the clearance of rizatriptan appeared to be mainly nonrenal.