Enoxaparin was well tolerated when administered subcutaneously or intravenously, and there appears to be no need to modify the currently recommended dose for obese volunteers.
Riluzole is a novel neuroprotective agent that has been developed for the treatment of amyotrophic lateral sclerosis. A series of studies was undertaken to establish its pharmacokinetics on single- and multiple-dose administration in young white male volunteers. The mean absolute oral bioavailability of riluzole (50-mg tablet) was approximately 60%. Maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC) values were linearly related to dose for the range studied. Cmax occurred at 1.0 hour to 1.5 hours after administration. Plasma elimination half-life appeared to be independent of dose. After repeated administration of 100 mg riluzole for 10 days, some intraindividual variability in bioavailability was seen. A high-fat meal significantly reduced the rate (tmax = 2 hours compared with 0.8 hours; Cmax = 216 ng.mL-1 compared to 387 ng.mL-1) and extent of absorption (AUC = 1,047 ng.hr.mL-1 versus 1,269 ng.hr.mL-1). With multiple-dose administration, riluzole showed dose-related absorption, although the terminal plasma half-life was prolonged slightly. Steady-state plasma concentrations were achieved within 5 days. Steady-state trough plasma concentrations were significantly higher with a 75-mg dose twice daily than with a 50-mg dose three times daily, although AUC values did not differ.
The peripheral distribution of spiramycin and metronidazole, which are combined in the proprietary drug "Rodogyl", has been studied in gingival fluid, saliva and blood after a single administration to 12 healthy volunteers and after repeated administration to 4 patients with recurring severe periodontitis. Analysis of the 2 antibiotics have been performed at regular intervals during the 24-h period immediately following the administration to the volunteers and after the 1st and the 15th days of repeated administration to the patients. The results show that gingival fluid contains concentrations of spiramycin and metronidazole higher than those needed to inhibit the growth of periodontopathic bacteria. Spiramycin was found at higher concentrations in GCF than in blood, although this feature was not found for metronidazole, which was administered simultaneously and showed similar concentrations in both fluid and serum. Such high concentrations persist for a long time, and suggest the potential of this compound in the treatment of severe cases of periodontitis.
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