Influence of Renal Failure on Ciprofloxacin Pharmacokinetics in Rats

Abstract

Ciprofloxacin pharmacokinetics have been shown to be modified in patients with renal failure (e.g., the intestinal secretion of ciprofloxacin is increased). This study investigated the influence of renal failure on the pharmacokinetics of ciprofloxacin following oral and parenteral administration to rats of a dose of 50 mg/kg of body weight. After parenteral administration, only renal clearance (CLR) was reduced in nephrectomized rats (5.3 ± 1.4 versus 17.8 ± 4.7 ml/min/kg, P< 0.01, nephrectomized versus control rats). However, nonrenal clearance was increased in nephrectomized rats (32 ± 4 versus 15 ± 5 ml/min/kg, P < 0.01, nephrectomized versus control rats), suggesting compensatory mechanisms for reduced renal function. After oral administration, apparent total clearance and CLR were reduced (P < 0.01) in nephrectomized rats (117 ± 25 and 6.8 ± 4.4 ml/min/kg, respectively) compared with the values for control rats (185 ± 9 and 22.6 ± 5.3 ml/min/kg, respectively) and the area under the concentration-time curve was higher (P < 0.01) for nephrectomized rats (436.3 ± 90.5 mg · min/liter) than for control rats (271.3 ± 14.3 mg · min/liter). Terminal elimination half lives in the two groups remained constant after oral and parenteral administration. These results suggest an increased bioavailability of ciprofloxacin in nephrectomized rats, which was confirmed by a nonlinear mixed-effect model.

Effects of Berberine and Hwangryunhaedok-Tang on Oral Bioavailability and Pharmacokinetics of Ciprofloxacin in Rats

“…The initial plasma concentration of ciprofloxacin was 4.14 ± 1.31 μ g/mL at 5 min posttreatment and detected up to 8 h. The mean values of t 1/2 λ z and AUC 0→ ∞ were 1.15 h and 4.62 h· μ g/mL, respectively. These data are consistent with other reports [ 21 ].…”

Inhibitory Effects of Multiple‐Dose Treatment with Baicalein on the Pharmacokinetics of Ciprofloxacin in Rats

“…Baicalein (80 mg/kg/day) reduced the F rel of ciprofloxacin by 70.4%, but the elimination constant (λ z ), t 1/2λz , T max , and MRT were not affected. The pharmacokinetic parameters of ciprofloxacin in the control group were consistent with those reported by previous studies (Nouaille‐Degorce et al , ; Zhu et al , ).…”

“…In humans, ciprofloxacin is rapidly absorbed from the duodenum and jejunum by passive diffusion with ≤50% oral bioavailability (Harder et al , ). The excretion of ciprofloxacin occurs via the kidney (40–60%), hepatic metabolism (15–20%), biliary secretion (≤1%), and intestinal secretion (10–15%) and its oral bioavailability can be influenced by a number of factors (Nouaille‐Degorce et al , ). Ciprofloxacin is a substrate at one or more active transporters, including P‐glycoprotein (P‐gp), organic anion transporters (OAT), and OAT polypeptide (OATP/Oatp), that are associated with its intestinal secretion and uptake (Dautrey et al , ).…”

Preparation and evaluation of enrofloxacin microspheres and tissue distribution in rats

“…Ciprofloxacin is an active de-ethylated metabolite of ENR [ 20 ]. In addition to metabolic elimination, ENR is mainly excreted via tubular excretion and glomerular filtration [ 19 ].…”