Ciprofloxacin is routinely prescribed to treat a variety of infections, including those of the urinary tract. To achieve optimum therapeutic benefits of the drug, all of the factors which influence its pharmacokinetics and effectiveness need to be determined. This study investigated the urinary excretion kinetics of ciprofloxacin upon oral administration of a single dose of 250 mg at 1000 or 2200 h in 12 healthy human subjects in a crossover design. The urine samples were analyzed for unchanged ciprofloxacin by a sensitive high-performance liquid chromatography method. A significant decrease in the rate and extent of ciprofloxacin excretion following 2200 h (109.59 versus 53.8 mg [P < 0.05]) administration was observed. This result may be due to circadian changes in the factors affecting renal excretion and also probably metabolism of ciprofloxacin.
The pharmacokinetics of naproxen was studied in 12 healthy male volunteers after a single oral dose of 500 mg at 10:00 and 22:00 h. Ingestion of drug at 22:00 h delayed the occurrence of peak serum levels (p < 0.0212). None of the other pharmacokinetic parameters exhibited any significant diurnal variations.
SummaryThe chronopharmacokinetics of diltiazem were investigated after administration of a 60mg oral dose (immediate release capsule) at 4 different times over 24 hours (0600, 1200, 1800 and 2400h) to 8 healthy human volunteers in a randomised crossover study with a washout period of I week. Serum samples were analysed for unchanged diltiazem using high performance liquid chromatography. Pharmacokinetic parameters were calculated using model independent methods. A significant decrease in the Cmax (F = 6.52, p < 0.002) and AUCa-a (F = 3.26, p < 0.05) as well as an increase in the oral clearance (F = 3.62, P < 0.05) and apparent volume of distribution (F = 5.85, P < 0.01) were observed following administration at 0600h. Following the 2400h dose administration, the elimination half-life was significantly decreased as compared with that at the other dose times (F = 4.11, P < 0.025). These variations appear to be a result of time-
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