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.
Optimization of therapy by chronopharmacology requires knowledge of rhythmic manifestations of disease activity and chronopharmacokinetic data of the drugs prescribed. Rhythmic functioning of the cardiovascular system in healthy and diseased subjects is manifested as circadian rhythms in blood pressure, cardiac output, heart rate, etc. The disposition of several cardiovascular drugs in man has been reported to be time-dependent. This study reports the effect of time of administration on the disposition of pentoxifylline. Twelve healthy volunteers were treated with 400 mg pentoxifylline orally at 0100, 0700, 1300 and 1900 h in a randomized crossover Latin-square design with a wash-out period of one week. Serum samples were analysed for unchanged pentoxifylline by HPLC. Pharmacokinetic parameters were calculated using a model-independent method. The mean values of various pharmacokinetic parameters after drug treatment at these times were, respectively: maximum plasma concentration (Cmax) 485+/-174, 646+/-175, 735+/-271 and 781+/-217 ng mL(-1); time to reach the maximum plasma concentration (Tmax) 1.90+/-0.39, 1.66+/-0.4, 1.31+/-0.41 and 1.32+/-0.44 h, mean residence time (MRT) 3.8+/-0.8, 2.9+/-0.5, 2.9+/-0.4 and 2.7+/-0.3 h, elimination half-life (t1/2) 1.93+/-0.86, 1.23+/-0.3, 1.39+/-0.3 and 1.23+/-0.18 h and volume of distribution at steady state (VdSS/f) 11991+/-4862, 8823+/-3484, 8275+/-2357 and 7063+/-1950 mL kg(-1). The mean Cmax value was significantly (P < 0.05) lower after drug administration at 0100 h than after other time-points whereas mean Tmax, MRT, VdSS/f and t1/2 values were significantly (P < 0.05) higher. These variations might be because of time-dependent changes in absorption and biliary excretion of pentoxifylline and should be borne in mind when designing sustained action dosage forms for the drug.
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