No abstract

The pharmacokinetics of sparfloxacin at oral doses of 200, 400, 600, and 800 mg were studied in 12 healthy volunteers in a randomized double-blind crossover study. Each dose administration was separated by a 1-week washout period. Plasma and urine samples were collected up to 120 hours postdosing, for determination of free and total (free plus glucurono-conjugated) sparfloxacin levels by high-performance liquid chromatography assay and ultraviolet detection. Mean Cmax values ranged from 705 +/- 158 to 1966 +/- 620 ng/mL for the 200 to 800 mg doses, at median tmax ranging from 4 to 5 hours. A slight decrease of sparfloxacin bioavailability with increasing dose was observed because AUC was 87% to 88% of the expected area when the dose was doubled. The elimination half-life values were constant over the dose range (with values ranging from 18 to 21 hours) as well as the renal clearance. The metabolic ratio conjugated/free drug was not modified by increasing dose.

The pharmacokinetics of sparfloxacin were studied in 14 renal failure patients (group I, 7 with creatinine clearance of >10 to 30 ml/min; and group II, 7 with creatinine clearance of '10 ml/min) after a single oral dose of 400 mg. Plasma and urine samples were collected up to 144 h postdosing for determination of parent and total (parent-plus-glucuronide-conjugated) sparfloxacin levels, by high-pressure liquid chromatography assay and UV detection. The A large number of fluorinated 4-quinolones has been developed in recent years. While there are differences in the details of their antimicrobial activity, they are all much more active in vitro than earlier 4-quinolone compounds. Most exhibit the greatest activity against aerobic gram-negative organisms and are generally less active against staphylococci, streptococci, and anaerobia. Sparfloxacin [5-amino-1-cyclopropyl-6,8-difluoro-1,4-dihydro-7-(cis -3,5 -dimethyl -1 -piperazinyl) -4 -oxoquinoline-3-carboxylic acid; AT-4140; RP 64206] is a new quinolone with broad antibacterial activity. It is more active than ciprofloxacin against staphylococci, streptococci, and enterococci. Sparfloxacin is more active than ciprofloxacin against isolates in the Bacteroides fragilis group and against clostridia. On the other hand, sparfloxacin is less active than ciprofloxacin against members of the family Enterobacteriaceae or against Pseudomonas aeruginosa (1, 6, 7, 13).Studies of young subjects with normal renal function have shown that sparfloxacin kinetics are mainly characterized by a long elimination half-life (tl2) of 16 to 20 h (5, 10), low protein binding (45%) (9), and sole transformation into one inactive glucuronide conjugate (12). The elimination is mainly nonrenal, since parent and conjugated drug urinary excretions account for approximately 30% of the dose. The purpose of the present study was to investigate the pharmacokinetics of sparfloxacin in cases of renal insufficiency after a single oral dose of 400 mg. MATERIALS AND METHODSFourteen subjects with chronic renal impairment were included in the study, which was approved by the Ethical Committee

The pharmacokinetics and tolerability of the novel antiexcitatory agent, riluzole, were compared in 18 healthy elderly and 18 healthy gender‐ and weight‐matched young volunteers. All participants received riluzole 50 mg twice daily (the recommended dosage for patients with amyotrophic lateral sclerosis), administered orally for 5 days. The pharmacokinetics of riluzole, determined on the morning of the 5th day of dosing, were not significantly affected by age or gender. The mean terminal elimination half‐life (t1/2), however, was statistically significant between elderly and young subjects. Riluzole was well tolerated upon repeat dose administration. Headache was the most frequent adverse event reported, and there was no overt difference in the type, frequency, or severity of adverse events between elderly and young volunteers or between genders. In conclusion, these results indicate that no dosage adjustments of riluzole are required in the elderly.