Pharmacokinetics Of Cefepime In Five Ethnic Groups In China

Objective To investigate and compare the pharmacokinetics of cefepime in healthy volunteers of different Chinese nationalities (including Han, Mongolia, Uigur, Korea and Muslim) and genders. Then, we study the population pharmacokinetics of cefepime based on the concentration of five nationalities. In addition, the research would provide instruction and help for the usage of cefepime safely, reasonably and effectively to both clinic and remedy of battle wound.Methods A single dose of 1.0 g cefepime was given under fasting conditions to ten healthy volunteers (five male and five female) of each Chinese nationalities above. Plasma samples were obtained before dosing and at various predetermined time points after a single intravenous administration up to 10.5 hours. A simple, accurate and sensitive HPLC-UV method was developed to determine the plasma concentration of cefepime. The pharmacokinetic parameters were calculated by DAS 2.0 software and were compared by SPSS 11.5 software. Finally, nonlinear mixed-effect model (NONMEM) was applied to study population pharmacokinetics of cefepime.Results (1)The PK parameters of cefepime in five nationalities (including Han, Mongolia, Uigur, Korea and Muslim) after a single intravenous administration of 1.0 g cefepime were:t1/2β(1.97±0.204), (2.09±0.694), (2.06±0.331), (2.40±0.655) and (1.94±0.236) h; Vd (20.2±4.35), (19.8±7.52), (18.7±5.28), (19.2±3.79) and (21.3±4.81) L; CL (7.10±1.05), (6.58±1.08), (6.24±0.91), (7.16±1.76) and (7.55±1.29) L·h-1; AUC0-10.5h (137±23.0), (149±22.6) (162±24.2), (140±28.7) and (129±23.0) mg·h·L-1; AUC(0-∞) (140±23.8), (152±20.9) (166±25.5),(142±29.8)and(133±23.8)mg·h·L-1;Cmax(68.8±10.4),(75.3±13.7),(83.2±10.3), (73.8±9.59)and(62.9±10.7)mg·L-1. (2) The PK parameters of 25 male volunteers and 25 female volunteers after a single intravenous administration of 1.0 g cefepime were:t1/2β(2.06±0.542)and (2.13±0.443) h; Vd (20.7±4.36) and (19.0±5.82) L; CL (7.48±1.38) and (6.37±0.987) L·h-1; AUC0-10.5h (131±21.3) and (156±24.1) mg·h·L-1; AUC(0-∞)(134±22.3) and (159±24.8) mg·h·L-1; Cmax (66.9±9.14) and (79.0±12.7) mg·L-1.(3) Results of statistical analysis showed that there were no significant differences on the PK parameters Vd, CL, lnAUC, t1/2βof different nationalities and Vd, t1/2βof different genders, but significant on lnCmax of different nationalities and CL, lnAUC, lnCmax of different genders. Then, we found there was high linear correlation (P < 0.01) between weight and CL, lnAUC and lnCmax. The differences of the PK parameters above became insignificant after normalized by weight.Conclusion (1) Normalized by body weight, the differences of ethnicity among five nationalities and gender had no significant influence on the pharmacokinetics of cefepime.(2) In clinic and remedy of battle wound, we should adjust the dosage of cefepime according to the body weight of patient in order to use it safely, reasonably and effectively.