Pharmacokinetics And Relative Bioavailability Of Cefdinir Dispersible Tables Among Healthy Chinese Person

It is well known to all that theβ-lactams(penicillin,cephalosporins, and atypicalβ-lactams) are at the lead position in antibiotic market in the world. Because of theabuse ofβ-lactams, bacterial resistance has become a growing phenomenon. It isinevitable to study new antibiotics which are resistant toβ-lactamases. At the lastestβ-lactams antibiotics,cefdinir is acquired from the cefixime,It modified thecefixime's structure and compensate the third generation of cephalosporins'weakfunction to the Gram-negative bacteria. It has enough antibisis ability on the firstphase of treatment to avoid the resistant emergence. So we consulted cefdinirdispersible tablets produced by SanDongYiKang Medicine Limited Company andstudied pharmacokinetics and relative bioavailabity of dispersible cefdinir tabletsamong healthy Chinese persons. It is expected that it could provide reference for theuse of medicine in clinic.Objective To study the pharmacokinetics academic foundation and use of cefdinirin Chinese healthy volunteers.Methods An open, randomized and crossover study with one week washoutinterval was performed in 20 healthy volunteers. The reference formulation wasmanufactured by Fujisawa Toyama Co.Ltd.Takaoka Plant. The test formulation wasmanufactured by SanDongYiKang Medicine Limited Company. Cefdinir standard referenceformulation (400mg) and the test formulation (400mg) were given to 20 healthy malevolunteers in a randomized cross-over study. The interval was one week. None of thesubjects had a taken any other drugs for at least 2 weeks before the study and did not take any other drugs during the study. Their normal health status were judged on thebasis of a physical examination with screening blood chemistries, including acomplete blood count and liver function test,urinalysis and electrocardiogramperformed before the study. Volunteers were given medicine with tepid water of200ml in the morning after an overnight fast and were given standard food of low fatand low protein at 4h after medication. Venous blood samples(2ml each) werecollected into tubes, immediately before the drug administration and at 1, 1.5, 2, 2.5, 3,3.5, 4, 5, 6, 8, 10,12 hours after dosing. The samples were spun after the quiet 2 hours,and the blood plasma were stored at -20℃until assayed. The concentration in bloodplasma were detected with improved microbiology method. The tested microorganismwas Micrococcus Luteus 28001.The blood plasma concentration-time data were disposed with 3p97 program.The peak connection(C_max) and the peak time (T_max) of ritonavir were determinedfrom the respective observed concentration-time data. The area under the curve(AUC)were calculated by the linear trapezoidal method. The data are expressed as meanvalues±SD throughout the paper. Difference in pharmacokinetic data betweendomestic formulation and imported formulation were evaluated statistically by use ofa two-sample test. P value of＜0.05 was considered to statistically significant.Results It has been studied that the cefdinir pharmacokinetics in Chinesehealthy volunteers by using improved microbiology method. The results show thatthis method was specific and selective. In blood plasma and impurity substance inblood plasma didn't interfere with determination of cefdinir. Obtained linearregression equation of cefdinir is lgC=0.0734D-1.5013(r=0.9962).The lowerlimit of quantization is 0.2mg L^-1. The line range is 0.2-3.2 mg L^-1. The recoveries,difference intra-day and intra-day all meet with the examination of living creaturesample.The study results showed that the data of the two formulations were fitted to aone-compartment open model in healthy volunteers. Compared with standardreference formulation, the relative bioavailability of cefdinir is (95.93±16.01)% (F₀^t)and(96.03±14.89)ï¼…(F₀^∞). The pharmacokinetic parameters of standard referenceformulation and cefdinir were T_max(3.60±0.48) h, (3.48±0.53)h; C_max(2.15±0.26)mg L^-1, (2.10±0.32) mg L^-1. T_1／2ke (2.33±0.41) h, (2.41±0.39)h. AUC₀^t (10.05±1.72)mg h L^-1, (9.51±1.65) mg h L^-1. AUC₀^∞(11.01±1.81) mg h L^-11, (10.43±1.62)mg h L^-1. C_max, AUC₀^t, AUC₀^∞between the two formulation of cefdinir wereanalyzed with a statistic analysis of ANOVA and two one-side test statical analysis.T_max is analyzed with nonparametric statistics.The results show that C_max, AUC₀^t, AUC₀^t and T_max of the two formulation are bioequivalent.Conclusion1. The standard reference and test formulation of cefdinir were fitted to aone-compartment open model in healthy volunteers.2. The two different forms of cefdinir are bioequvalent.