Pharmacokinetic and bioequivalence comparison of a single 100-mg dose of cefteram pivoxil powder suspension and tablet formulations: a randomized-sequence, open-label, two-period crossover study in healthy Chinese adult male volunteers.
BACKGROUND
Cefteram pivoxil (CFTM-PI) is an oral antibiotic available in powder suspension and tablet formulations indicated in China for the treatment of bacterial infections. Although these 2 formulations are marketed in China, published information regarding their pharmacokinetics and bioequivalence in the Chinese population is not available.


OBJECTIVE
The aim of this study was to compare the pharmacokinetics and bioequivalence of the powder suspension (test) and tablet (reference) formulations of CFTM-PI 100 mg available in China.


METHODS
This single-dose, randomized-sequence, open-label, 2-period crossover study was performed at the Nanjing First Hospital of Nanjing Medical University. Eligible subjects were healthy male volunteers who were randomly assigned at a 1:1 ratio to receive a single 100-mg dose of the test or reference formulation, followed by a 1-week washout period and administration of the alternate formulation. The study drugs were administered after a 12-hour overnight fast. Plasma was assayed using a high-performance liquid chromatography method. For analysis of pharmacokinetic properties, including C(max), AUC from time 0 (baseline) to 6 hours (AUC(0-6)), and AUC from baseline to infinity (AUC(0-infinity)), blood samples were obtained at intervals over the 6-hour period after study drug administration. The formulations were considered bioequivalent if the log-transformed ratios of C(max) and AUC were within the predetermined equivalence range (80%-125%) as established by the US Food and Drug Administration (FDA). Tolerability was assessed by monitoring vital signs and laboratory tests (hematology, blood biochemistry, hepatic function, and urinalysis), and by questioning subjects about adverse events (AEs).


RESULTS
Twenty-four Chinese male subjects (mean [range] age,24.2 [23-32] years;weight,64.3 [58-67] kg; height, 172 [167-185] cm) enrolled; all completed the study. No period or sequence effect was observed. The 90% CIs for the log-transformed ratios of C(max), AUC(0-6;), and AUC(0-infinity) were 96.5 to 120.1, 95.7 to 110.2, and 96.2 to 110.4, respectively (all, P>0.05). Similar results were found for the data without log-transformation. No AEs occurred or were reported during the study.


CONCLUSIONS
In this small study in healthy Chinese adult male volunteers, a single 100-mg dose of the powder-suspension formulation was bioequivalent to a single 100-mg dose of the tablet formulation based on the US FDA's regulatory definition (rate and extent of absorption). Both formulations were well tolerated.
Zou
Jianjun
J
Department of Clinical Pharmacology, Nanjing First Hospital of Nanjing Medical University, Nanjing, China.
Di
Bin
B
Wu
Chun Yong
CY
Hu
Qin
Q
Li
Jian Hua
JH
Zhu
Yubing
Y
Fan
Hongwei
H
Xiao
DaWei
D
Wang
Guang Ji
GJ
D000284:Administration, Oral; D000328:Adult; D001424:Bacterial Infections / Q000097:blood / Q000188:drug therapy; D015281:Cefmenoxime / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D002681:China; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004339:Drug Compounding; D004361:Drug Tolerance; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D011208:Powders; D012016:Reference Values; D013607:Tablets; D013810:Therapeutic Equivalency
D011208:Powders; D013607:Tablets; C046817:cefteram pivoxil; D015281:Cefmenoxime