Effect of ciprofloxacin on the disposition of 14C-dideoxyinosine-derived radioactivity in the rat.
The potential for the antibacterial agent ciprofloxacin to interfere with the disposition of the antiviral agent dideoxyinosine (ddI) was evaluated in adult male Wistar rats. The combination group (n = 10) was dosed orally with 100 mg/kg ciprofloxacin in water every 12 h for three consecutive doses. Thirty minutes after the last dose, a bolus IV injection of 50 mg/kg 14C-ddI in physiologic saline was given over 7-10 sec through the penile vein. The control group (n = 8) received a single dose of IV 14C-ddI. Blood, urine and fecal samples were collected from 0-4 h, and tissue samples were removed at 4 h after ddI administration. The disappearance of 14C from blood followed the kinetics of a two-compartment model with bolus input and first-order output. The following pharmacokinetic parameters (mean +/- SD) were calculated based on total blood radioactivity for the 14C-ddI alone and combination groups, respectively: blood clearance 13.5 +/- 2.0 vs. 12.7 +/- 1.5 ml/min/kg, terminal disposition half-life 49.9 +/- 2.2 vs. 49.0 +/- 6.0 min, steady-state volume of distribution 891 +/- 134 vs. 825 +/- 126 ml/kg, mean residence time 66.2 +/- 3.1 vs. 65.0 +/- 7.8 min (the power to detect a 20% decrease in the above parameters, relative to the reference ddI alone, was > 85% at the 5% significance level), percentage of administered dose recovered in urine 62.2 +/- 9.8% vs. 56.6 +/- 13.0%. Most of the radioactivity in tissues was concentrated in the liver, adrenal, spleen and kidney. Except for significant decreases (p < 0.05) in the levels of 14C in skeletal muscle and cecum of combination treated rats, the coadministration of ciprofloxacin showed no differences in either the tissue levels of 14C or the pharmacokinetic parameters of 14C-ddI-derived radioactivity. The results obtained with total 14C measurements suggest that ciprofloxacin does not alter the disposition of ddI in the rat, although unchanged ddI was not determined.
Gallicano
K D
KD
Bureau of Drug Research, Sir Frederick Banting Research Centre, Ottawa, Ontario, Canada.
Buttar
H S
HS
Moffatt
J H
JH
D000284:Administration, Oral; D000818:Animals; D001774:Blood Chemical Analysis; D002250:Carbon Radioisotopes; D002939:Ciprofloxacin / Q000494:pharmacology*; D016049:Didanosine / Q000493:pharmacokinetics*; D004347:Drug Interactions; D006207:Half-Life; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution; D016482:Urinalysis
D002250:Carbon Radioisotopes; D002939:Ciprofloxacin; D016049:Didanosine