Clinical Pharmacokinetics of Ciprofloxacin

Abstract

Compared with nalidixic acid, ciprofloxacin is representative of a newer, more potent class of quinolones, termed the fluoroquinolones. It is available in both oral and parenteral dosage forms. The primary target of quinolone activity appears to be the bacterial DNA gyrase enzyme, which is a member of the class of type II topoisomerases. Bacterial do not acquire resistance to fluoroquinolones through mechanisms that are plasmid or R-factor mediated and, additionally, the quinolones do not appear to be vulnerable to degradation by bacterial inactivating mechanisms. Rather, bacterial resistance to ciprofloxacin occurs either through chromosomal mutation in the target enzyme DNA gyrase or through mutations that alter drug permeability into the bacterial cell. Ciprofloxacin and the fluoroquinolones in general are no more likely to select resistant mutant than are aminoglycosides or beta-lactam antibiotics. Ciprofloxacin displays in vitro activity against most Gram-negative and many Gram-positive pathogenic bacteria, many of which are resistant to a wide range of antibiotics. This finding is of considerable potential clinical significance. High pressure liquid chromatography (HPLC) and microbiological agar diffusion assays have been routinely used to quantify ciprofloxacin concentrations in biological fluids. Both methods are reproducible and accurate for serum but HPLC is recommended for other specimens because of the presence of microbiologically active metabolites. Absorption after oral administration is rapid and can be satisfactorily described as a zero-order process; peak serum ciprofloxacin concentrations (Cmax) are reached in approximately 1 to 2 hours. Concomitant administration of food does not cause clinically significant impairment of absorption and may be helpful in minimising gastric distress caused by the drug. A linear relationship between serum ciprofloxacin concentrations and the dose administered either orally or intravenously has been reported. The absolute bioavailability of ciprofloxacin is approximately 70%. The volume of distribution is large with a steady-state range after oral or intravenous dosing of 1.74 to 5.0 L/kg reflecting penetration of the drug into most tissues. Nonrenal clearance accounts for approximately 33% of the elimination of ciprofloxacin; to date, 4 metabolites have been identified. A first-pass effect has been reported but is thought to be clinically unimportant. Faecal recovery of ciprofloxacin accounts for approximately 15% of an intravenous dose. Nonrenal elimination includes metabolic degradation, biliary excretion and transluminal secretion across the enteric mucosa. Glomerular filtration and tubular secretion account for approximately 66% of the total serum clearance. The terminal disposition half-life (t1/2) is about 3 to 4 hours.(ABSTRACT TRUNCATED AT 400 WORDS)

Efficacy and Safety of a Novel Once-Daily Extended-Release Ciprofloxacin Tablet Formulation for Treatment of Uncomplicated Urinary Tract Infection in Women

“…The low frequencies of adverse events (12.7% for ciprofloxacin ER and 14.7% for ciprofloxacin IR) are similar to the approximately 15% frequency reported for ciprofloxacin IR in previous studies conducted in the United States (27). The rates for a marketed once-daily extended-release formulation of ciprofloxacin are approximately the same as for ciprofloxacin IR (13).…”

“…Trimethoprim-sulfamethoxazole (TMP-SMX) is currently the first-line treatment for acute uncomplicated UTI (uUTI) or acute uncomplicated bacterial cystitis, but bacterial resistance to TMP-SMX is increasing (9,11,14,19,22), and therefore, fluoroquinolones are recommended as the first-line therapy in areas where resistance to TMP-SMX is high (Ͼ10% to 20%) (29). Ciprofloxacin, a fluoroquinolone antimicrobial agent with a broad spectrum of activity against both gramnegative and gram-positive bacteria, is an effective treatment for a wide variety of bacterial infections, including uUTI (5,7,27). However, gastrointestinal (GI) adverse events, such as nausea and diarrhea, remain the most common cause of discontinuation of ciprofloxacin therapy (5,7).…”

Disposition Kinetics and Optimal Dosage of Ciprofloxacin in Healthy Domestic Ruminant Species

“…For the majority of organisms that are susceptible to ciprofloxacin, the reported MIC values are 0.02-0.3 µg/ml plasma levels that may be accepted as optimal MIC (Alestig 1990;Vance-Bryan et al 1990;Giguère et al 1996;Kaartinen et al 1997;Saini and Srivastava 2001). During the course of therapy, plasma level of an antibiotic should not fall below a minimum inhibitory concentration at the end of a certain dosing interval.…”

Antimicrobial Stewardship in the Microbiology Laboratory: Impact of Selective Susceptibility Reporting on Ciprofloxacin Utilization and Susceptibility of Gram-Negative Isolates to Ciprofloxacin in a Hospital Setting

“…Since 80% of E. coli isolates were from the urinary tract, selective reporting in this group likely drove the majority of changes in antibiotic utilization. Additionally, there may be some value to reporting ciprofloxacin for nonurinary isolates, due to the good bioavailability and tissue penetration of this agent for deepseated infections (14).…”