Absolute oral bioavailability of ciprofloxacin

Abstract

We evaluated the absolute bioavailability of ciprofloxacin, a new quinoline carboxylic acid, in 12 healthy male volunteers. Doses of 200 mg were given to each of the volunteers in a randomized, crossover manner 1 week apart orally and as a 10-min intravenous infusion. Ciprofloxacin is a new quinoline carboxylic acid with a broad spectrum of activity encompassing the Enterobacteriaceae, Pseudomonas aeruginosa, and Staphylococcus aureus (methicillin susceptible and resistant) (2). Ciprofloxacin has both oral and parehteral dosing forms (4, 5), possibly allowing initial parenteral therapy for serious infections followed by oral therapy, thereby simplifying care and decreasing costs. We evaluated the pharmacokinetics of the oral and intravenous forms of ciprofloxacin, as well as the extent and reliability of absorption. Other investigators have addressed this to some extent but have used a microbiologic assay for their determination of drug concentration in serum (6). Consequently, we undertook a randomized, crossover design evaluation of the bioavailability of ciprofloxacin in 12 healthy volunteers. MATERIALS AND METHODSStudy design. Twelve nonobese healthy males between 21 and 29 years of age were randomly assigned to receive 200 mg of ciprofloxacin either intravenously as a 10-min infusion in 200 ml of normal saline or orally as two 100-mg tablets after an overnight fast. In the subsequent week, volunteers were crossed over to the alternate regimen. No Drug assay. Ciprofloxacin concentration was measured in serum and urine by high-pressure liquid chromatography, a variant of the assay of Gau et al. (3). The serum assay used protein precipitation, reverse-phase high-pressure liquid chromatography, and fluorometric detection. The urine assay used sample dilution followed by direct injection. Quinine was used as an internal standard. A Waters C18 ,uBondapak reverse-phase column was used for the assay. The mobile phase consisted of 27% methanol, 0.8% tetrahydrofuran, and 0.067 M phosphate buffer (pH 3.0). A flow rate of 1.3 ml/min was used. The column was heated to 500C.The assays were determined to be linear between 0.01 and 1 ,ug/ml for serum and between 0.025 and 1.5 pg/ml for urine. The sensitivities of the assays were at least 0.01 p.g/ml.

Pharmacokinetics of intravenously administered ciprofloxacin in patients with various degrees of renal function

“…Patients in group 1 had measured creatinine clearances greater than 6 liters/h per 1.73 M2. Group 1 volunteers were a subset (8 of 12) of previously reported normal volunteers receiving 200 mg of ciprofloxacin intravenously (4). Group 2 subjects had creatinine clearances greater than or equal to 3.6 and less than 6.0 liters/h per 1.73 M2.…”

Effect of dose size on bioavailability of ciprofloxacin

“…and up to 1 g orally. Previous work at the University of Maryland with healthy subjects given 200 mg orally has revealed that the drug is reliably (approximately 70%) bioavailable (2). Because of the discrepancy in dose sizes available for the i.v.…”

“…no. 1002,1985) and the absolute bioavailability of ciprofloxacin (2). Each subject had normal hepatic and renal function indices and gave written informed consent in accordance with institution guidelines.…”

Steady-state pharmacokinetics of intravenous and oral ciprofloxacin in elderly patients

“…Compared with data derived from studies of young adult volunteers receiving single doses of intravenous ciprofloxacin (4,5,8,13,20), CLs, CLR, and V., were decreased in our study patients. In addition, the mean Cm.…”

“…The pharmacokinetics of ciprofloxacin have been characterized in adults with normal and impaired renal function after single and multiple dose administration (4,5,8,9,11,13,14,16,20 ance of ciprofloxacin and a decreased apparent volume of distribution of the drug in elderly subjects.…”