PHARMACOKINETICS OF CIPROFLOXACIN .2. COMMUNICATION - DISTRIBUTION TO AND ELIMINATION FROM TISSUES AND ORGANS FOLLOWING SINGLE OR REPEATED ADMINISTRATION OF [C-14] CIPROFLOXACIN IN ALBINO-RATS

  • 1 January 1986
    • journal article
    • research article
    • Vol. 36-2  (10) , 1503-1510
Abstract
1-Cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-[U-14C]piperazinyl)-3-quinoline carboxylic acid (ciprofloxacin, Bay o 9867; designated tradename: Ciprobay) was administered to male and to pregnant albino rats with single intravenous or oral doses of 5 or 10 mg/kg body weight and with repeated oral doses of 5 mg/kg (7 consecutive daily administrations to male rats). Following a single intravenous administration the [14C]ciprofloxacin related radioactivity was distributed rapidly and differentiated to the body. Compared to plasma light concentrations were determined in kidney, liver, skeleton muscle, pancreas, testes and cartilage, low concentrations occurred in brain and adipose tissue. In some selected tissues radioactivity was largely due to unchanged [14C]ciprofloxacin (57% to 100%). A good penetration of total radioactivity into tissues and organs with a similar distribution pattern as detected after intravenous dosing also occurred after a single oral administration. Highest concentrations were determined 1 h after dosing. Compared to plasma most tissues and organs showed higher concentrations and higher AUC-values. For brain and eye low values were determined. Compared to plasma a longer mean residence time of radioactivity was calculated for brain, eye, eye-wall, testes and blood cells. 6 d after single administration the radioactive residues in the body exclusive gastrointestinal tract amounted to less than 0.1% of the dose. Following a seven-day treatment the distribution pattern of total radioactivity in the body did not differ essentially from that after single dosing. Compared to single dosing AUC-values higher by the factor 2 to 4 were calculated after repeated administration for plasma and most of the tissues and organs. After repeated administration mean residence time for radioactivity was not altered for plasma whereas a slight increase was observed for most tissues. Following repeated administration radioactive residues in the body exclusive gastrointestinal tract amounted 6 d after the last administration to less than 0.7% of the last dose. After single administration the [14C]ciprofloxacin related radioactivity passed through the placental barrier at low degree. Compared to maternal body in fetuses largely lower concentrations of radioactivity were determined. Radioactivity was eliminated from maternal body and fetuses at a similar rate.