Pharmacokinetics of intravenously administered ciprofloxacin

Abstract

A 100-mg dose of ciprofloxacin was given as an intravenous bolus injection to each of six healthy volunteers, after which the levels of this agent were measured in serum, blister fluid, and urine, After administration, distribution of ciprofloxacin was very rapid, and the mean distribution volume was very large (177 liters). The mean terminal serum half-life was 4.0 h. The agent penetrated blister fluid rapidly, with the mean maximum level being 0.53 ,ug/ml at 30 min, after which time the blister levels exceeded those in serum. The 48-h urinary recovery of ciprofloxacin was about 80%.Ciprofloxacin is a new quinoline carboxylic acid antimicrobial agent which can be given by either the oral or parenteral route (1, 5). It has high in vitro activity against a wide range of pathogens, including members of the family Enterobacteriaceae, Pseudomonas aeruginosa, and grampositive cocci, which includes those strains that are resistant to aminoglycosides and other commonly used agents such as the broad spectrum P-lactam antibiotics.The purpose of this study was to investigate the pharmacokinetic properties of this compound after intravenous administration and to compare the results with those obtained after oral administration (2). The penetration of the agent into chemically induced blister fluid, which has been shown to be similar in composition to the exudate of a mild inflammatory reaction (5), was also investigated. MATERIALS AND METHODSSix healthy male volunteers were entered into the study, five of whom had participated previously in a pharmacokinetic study on oral administration of ciprofloxacin (3). Approval for the study was obtained from the Dudley Road Hospital Ethical Committee, and informed consent was obtained from the volunteers. The ages of the subjects were 23 to 42 years (mean, 29.2 years) with a mean weight of 78.5 kg (range, 65 to 85 Kg) and a mean height of 176.6 cm (range, 169 to 186 cm). There were no significant episodes in their medical history, and biochemical and hematological profiles were normal. All subjects underwent physical examination the week before the study; the results were normal. On the night before the study, two 0.2% cantharides-impregnated plasters (1 by 1 cm) were applied to the volar surface of one forearm and taped in place. The subjects fasted from 10 p.m. the night before the study. At 8 a.m. on the day of the study, the subjects were given an intravenous injection of 100 mg of ciprofloxacin dissolved in 10 ml of distilled water. The subjects drank 200 ml of water in the first 2 h; thereafter, fluid was allowed ad libitum. Solid food was taken after 2 h.Blood was taken from an indwelling intravenous cannula at 5, 10, 15, 30, 45, 60, and 90 min and 2, 3, 4, 5, 6, 7, 8, and 12 h after drug administration. Urine samples were collected over 0 to 4, 4 to 8, 8 to 12, 12 to 24, and 24 to 48 h after administration. On the mornings at 72 and 96 h after drug administration, the first urine specimen of the day was also collected. The two blisters were sampled at 15, 30, and 60 min, hou...

Pharmacokinetics of single-dose oral ciprofloxacin in patients undergoing chronic ambulatory peritoneal dialysis

“…This is similar to the data reported for normal volunteers by Gonzalez et al (4), who obtained peaks of 3.41 to 4.21 ,ug/ml 1 to 1.5 h after a 750-mg dose. The mean terminal serum half-life of 16.8 h (range, 10.7 to 25.2) in our patients with end-stage renal disease patients is not unexpected and differs dramatically from the 3.9 to 6.6 h reported for normal subjects (2,8).…”

Pharmacokinetics of three oral formulations of ciprofloxacin

“…This finding cannot be explained by a high degree of plasma protein binding since ciprofloxacin is only 20% bound to plasma proteins (8). Ciprofloxacin is a large dipolar ion (molecular weight, 348) that is poorly lipophilic (9) and thus would not be likely to diffuse into saliva. Our data indicate that ciprofloxacin content in saliva, relative to that in serum, may be greater early in the dosing interval.…”

“…In a recent report by Wise et al. (9), the bioavailability of ciprofloxacin in five subjects was reported to be 71.7 ± 13.2% after a 500-mg oral dose and a 100-mg intravenous dose. Bioavailability was calculated by using AUC ratios corrected for dose.…”

Pharmacokinetics of ciprofloxacin in sheep after single intravenous or intramuscular administration

“…Inter-and intra-assay precisions, determined by injection of control standards, were 5 and 7% respectively. In humans, this model is also stat most widely used model for describing the pharmacokinetics of this drug after IV administration (8,27).…”