title: Pharmacokinetic differences between the epimers of cefotetan disodium after single intravenous injection in healthy Chinese volunteers.
abstract: The pharmacokinetic behaviors of the epimers of cefotetan disodium (R-CTT, S-CTT) after a single intravenous injection dose in healthy Chinese volunteers were explored in this study. In an open-label, randomized, three-way, cross-over study, 12 volunteers (6 females and 6 males) received a cross-over fashion doses of 0.5, 1.0, and 2.0 g of cefotetan disodium, separated by washout periods of 7 days. The plasma concentrations of both epimers were measured by validated high-performance liquid chromatography assays. Pharmacokinetic parameters of R-CTT, S-CTT, and total-CTT (R + S mixture) were calculated using a noncompartmental analysis. Generally, the R and S epimers showed different pharmacokinetic behaviors. Following 0.5, 1.0, and 2.0 g doses of cefotetan disodium, values of the total area under the plasma concentration-time curve (AUC(0-∞)) were 124.23 ± 19.54, 231.34 ± 39.34, and 459.09 ± 80.65 for R-CTT; 100.95 ± 14.19, 193.80 ± 30.42, and 372.66 ± 67.32 for S-CTT, respectively. Total body clearance values were 4.13, 4.43, and 4.46 L/h for R-CTT and 5.05, 5.28, and 5.50 L/h for S-CTT, respectively. Mean plasma elimination half-life (t (1/2)) values of R-CTT were 4.16, 4.13, and 4.01 h for 0.5, 1.0, and 2.0 g doses, respectively, and those of S-CTT were 3.15, 3.25, and 3.21 h. There were significant differences in t (1/2) between the two epimers (P < 0.05). The t (1/2) of R-CTT was 28% longer than that of S-CTT, which indicated that the elimination of the S-CTT was greater than that of the R-CTT. All treatments were well tolerated.
authors.affiliation: Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Meng-xiang
authors.initials: MX
authors.lastname: Su
authors.forename: Min-hong
authors.initials: MH
authors.lastname: Liu
authors.forename: Bin
authors.initials: B
authors.lastname: Di
authors.forename: Li-li
authors.initials: LL
authors.lastname: Huang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Jiang
authors.forename: Peng-cheng
authors.initials: PC
authors.lastname: Ma
authors.forename: Tai-jun
authors.initials: TJ
authors.lastname: Hang
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D015313:Cefotetan / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D013237:Stereoisomerism
chemical_list: D000900:Anti-Bacterial Agents; D015313:Cefotetan