High Performance Liquid Chromatographic Analysis and Pharmacokinetic Characteristics of ID-7181, a Novel Quaternary Ammoniopropenyl Cephalosporin, Following Intravenous and Intramuscular Injections to Rats

The purpose of the present study was to examine the pharmacokinetic characteristics of 7-[(z)-2-(5-amino-1,2,4-thiadiazol-3-yl) -2-methoxyiminoacetamidol -3-[ (E) -3- [(E)-(1-carbamoyl-1-propene-3-yl) 3-ethylmethylammonio]-1-propene-1-yl]-3-cepheme-4-carboxylate (CAS 206126-08-1, ID-7181), a novel quaternary ammoniopropenyl cephalosporin that contains two vinyl groups at the C-3 side chain, after being administered intravenously (i.v.) or intramuscularly (i.m.) to rats. An HPLC-based method was developed to analyze the ID-7181 levels in the plasma, bile, urine, feces, and tissue homogenates and validated in a pharmacokinetic study. The plasma concentration of ID-7181 decreased to below the quantifiable limit at 6 h after the i.v. administration to rats following doses of 2-10 mg/kg, yielding a t 1/2,β of 77.7-81.7 min. The values of the terminal phase t 1/2 after i.m. doses of 10-50 mg/kg were 79.3-127 min. The total plasma clearance (CL t ) decreased with the nonlinear pharmacokinetics with an increase in the i.m. dose from 10 to 50 mg/kg in rats, while it was not significantly altered after the i.v. dose. The bioavailability of the i.m. administered ID-7181 was 43-63 %. Of the various tissues tested, ID-7181 was mainly distributed in the kidney after the i.v. or i.m. administration. The ID-7181 concentrations in the kidney 0.5 h after being administered i.v. or i.m. were comparable to the plasma concentrations shortly after being administered i.v. or the C max after being administered i.m. However, the ID-7181 concentrations in the tissues 6 h after being administered i.v. or i.m. decreased to low levels. The amounts of ID-7181 in the urine 24 h after being administered i.v. or i.m. were 35-45 % of the initial doses. The corresponding values in the bile 6 h after being administered i.v. or i.m. were 0.5-1 % of the initial dose. In conclusion, ID-7181, administered i.v. or i.m., is mainly distributed to the kidney. By 6 h after i.v. or i.m. administration, the ID-7181 concentrations in the various tissues decreased to very low levels. Moreover, the majority of ID-7181 appeared to be excreted in the urine.