Pharmacokinetics of a cephalone (CQ-M-EPCA) in rats after oral, intraduodenal and intravenous administration.
As part of the development of a new series of antibacterial agents derived from coupling a beta-lactamic precursor with a fluoroquinolone and named cephalones, the pharmacokinetics of one derivate: CQ-M-EPCA in rats after intravenous, intragastric and intraduodenal routes, was carried out. After the IV injection of 20 mg/kg or 40 mg/kg of this cephalone, plasma concentrations at the time zero (Cp0) were 3.1 and 11.26 microg/ml, respectively. Plasma concentrations decreased rapidly to almost disappear in both instances. Forty-five minutes later, a surge in concentrations, in the 40 mg/kg group, with a maximal plasma concentration (Cpmax) of 2.97 microg/ml was observed. An elimination half-life (T1/2el) of 2.36 +/- 0.33 h. was calculated. The drug was undetected by the ninth hour. Intragastric administration of the drug resulted in Cpmax of 3.78 +/- 0.26 microg/ml with a time to reach Cpmax (Tmax) of 25 min and T1/2el = 3.22 h. Same variables after intraduodenal administration were Cpmax 4.71 microg/ml; Tmax 1h, and T1/2el 3.41 h. Outstandingly high bioavailabilities after intragastric and intraduodenal administration (169 and 246%, respectively), together with the shape of the concentration versus time profiles after IV administration suggest that the drug undergoes a complex redistribution phenomenon, while showing high tissue diffusion with an apparent volume of distribution of 3.33 l/kg.
Pérez-Guillé
B
B
Experimental Surgery Laboratory, Dr. Joaquín Cravioto Research-Tower, National Institute of Pediatrics (INP), Mexican Ministry of Health (SSA), Av. Iman, No. 1 Col. Insurgentes Cuicuilco, Mexico Cp 04530, Mexico.
Sumano
L H
LH
Villegas-Alvarez
F
F
Soriano-Rosales
R
R
González-Zamora
J F
JF
Jiménez-Bravo-Luna
M
M
Carmona-Mancilla
A
A
Ocampo
C L
CL
D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D004386:Duodenum / Q000378:metabolism; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006207:Half-Life; D007275:Injections, Intravenous; D007441:Intubation, Gastrointestinal; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D000900:Anti-Bacterial Agents; C495303:CQ-M-EPCA; D024841:Fluoroquinolones