Comparative pharmacokinetics of cefuroxime lysine after single intravenous, intraperitoneal, and intramuscular administration to rats.
OBJECTIVE
To compare the pharmacokinetic parameters of cefuroxime lysine, a new second-generation of cephalosporin antibiotics, after intravenous (IV), intraperitoneal (IP), or intramuscular (IM) administration.


METHODS
Twelve male and 12 virgin female Sprague-Dawley rats, weighing from 200 to 250 g, were divided into three groups (n=4 for each gender in each group). The rats were administered a single dose (67.5 mg/kg) of cefuroxime lysine via IV bolus or IP or IM injection. Blood samples were collected and analyzed with a validated UFLC-MS/MS method. The concentration-time data were then calculated by compartmental and non-compartmental pharmacokinetic methods using DAS software.


RESULTS
After IV, IP or IM administration, the plasma cefuroxime lysine disposition was best described by a tri-compartmental, bi-compartmental or mono-compartmental open model, respectively, with first-order elimination. The plasma concentration profiles were similar through the 3 administration routes. The distribution process was rapid after IV administration [t(1/2(d)), 0.10 ± 0.11 h vs 1.36 ± 0.65 and 1.25 ± 1.01 h]. The AUMC(0-∞) is markedly larger, and mean residence time (MRT) is greatly longer after IP administration than that in IV, or IM routes (AUMC(0-∞): 55.33 ± 20.34 vs 16.84 ± 4.85 and 36.17 ± 13.24 mg·h(2)/L; MRT: 0.93 ± 0.10 h vs 0.37 ± 0.07 h and 0.65 ± 0.05 h). The C(max) after IM injection was significantly higher than that in IP injection (73.51 ± 12.46 vs 49.09 ± 7.06 mg/L). The AUC(0-∞) in male rats were significantly higher than that in female rats after IM administration (66.38 ± 16.5 vs 44.23 ± 6.37 mg·h/L). There was no significantly sex-related difference in other pharmacokinetic parameters of cefuroxime lysine between male and female rats.


CONCLUSIONS
Cefuroxime lysine shows quick absorption after IV injection, a long retension after IP injection, and a high C(max) after IM injection. After IM administration the AUC(0-∞) in male rats was significantly larger than that in female rats.
School of Pharmacy, Shenyang Pharmaceutical University, China.
Long-shan
LS
Zhao
Ran
R
Yin
Bin-bin
BB
Wei
Qing
Q
Li
Zhen-yuan
ZY
Jiang
Xiao-hui
XH
Chen
Kai-shun
KS
Bi
D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002444:Cefuroxime / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D002853:Chromatography, Liquid; D005260:Female; D006207:Half-Life; D007273:Injections, Intramuscular; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008297:Male; D008954:Models, Biological; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D053719:Tandem Mass Spectrometry; D014018:Tissue Distribution
D000900:Anti-Bacterial Agents; C027301:cefuroxime lysine; D002444:Cefuroxime