Comparative Study on the Pharmacokinetic Bioequivalence of Two Intravascular Ceftriaxone Preparations
Kao-Pin Hwang1,Jwu-Maw Yang3,Bin-Nan Wu2,Jwu-Lai Yeh2, Yung-Da Yang4, Su-Fan Sou4 and Ing-Jun Chen2
1. Department of Pediatric, Kaohsiung Medical College
2. Department of pharmacology, Kaohsiung Medical College
3. Department of Pharmacy, Chia-Nan College of Pharmacy and Science
4. Department of Pharmaceutical Investigation, Panbiotic Laboratories
ABSTRACT
The pharmacokinetics and bioequivalence of two Ceftriaxone preparations, CefinR "Panbiotic" for I.M injection and RocephinR "Roche" , were compared in twelve healthy male volunteers. A 1g dose of Ceftriaxone disodium hemiheptahydrate was given intramuscularly in a balanced two-way cross-over study for CefinR and RocephinR groups. Blood samples were obtained at 0, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0 and 24.0 hours after the dosing. Ceftriaxone concentration in plasma was assayed by a high performance liquid chromatographic method using an UV detector. All the data was processed by SigmaPlotR and SigmaStatR computer software and the pharmacokinetic parameters were calculated , based on one-compartment model. The results revealed that the maximal concentration (Cmax) of CefinR and RocephinR was 118.89±15.59 and 120.02±15.04 μg/ml；the time to reach maximal concentration (Tmax) was 1.83±0.33 and 1.75±0.26 hr；the elimination rate constant (Ke) was 0.11±0.02 hr-1 for both；the elimination half life (T1/2, β) was 6.54±0.93 and 6.25±0.90 hr；the absorption rate constant (Ka) was 1.83±0.38 and 1.81±0.28 hr-1；the area under curve (from 0 to t hou-rs) (AUC0~t) was 1263.45±106.69 and 1218.86±118.30 μg hr/ml；the area under curve ( from 0 hour to infinity) (AUC0~∞∞) was 1405.97±138.87 and 1356.27±166.90 μg hr/ml；Cl/F was 0.71±0.07 and 0.75±0.09 (L/hr)；Vdβ was 8.49±1.21 and 8.11± 1.17(L), respectively. In order to strengthen the statistical evidence, the power of the test (1-β) was also calculated. According to the statically pharmacokinetic results, statistical power value, and the natural logarithmic transformation of Cmax and AUC, we conclude that CefinR manufactured by Panbiotic and RocephinR manufactured by Roche are bioequivalent.
Key words: Ceftriaxone, pharmacokinetics, bioequivalence