[Pharmacokinetics study of injected doripenemin healthy volunteers].

ABSTRACT

OBJECTIVE: To study the pharmacokinetics of injected doripenem in Chinese healthy volunteers, in order to optimize dosages for patients. METHODS: Twelve healthy volunteers were recruited in the threecross Latin square designed study. Participants received intravenous infusions of 0.25, 0.5 and 1.0 g doripenem sequentially in three periods at a random order. Plasma and urine doripenem were measured by HPLC-UV, using an internal standard method with meropenem for plasma samples and an external standard method for urine samples, respectively. Phoenix WinNonlin 6.1 pharmacokinetic software was used to calculate non-compartment pharmacokinetics parameters. SPSS 19.0 software was used for statistical analysis. RESULTS: A single dose infusion of 0.25, 0.5 and 1.0 g doripenemin 60 min produced the following respective parameters Cmax (11.81 +/- 1.52), (22.80 +/- 3.80) and (47.26 +/- 8.38) microg/mL, Tmax (60.42 +/- 1.44), (58.33 +/- 5.77) and (60.00 +/- 0) min, t(1/2) (63.48 +/- 10.51), (69.12 +/- 16.72) and (69.30 +/- 11.71) min, AUC(0-1), (1100.86 +/- 150.04), (2111.50 +/- 359.58) and (4359.50 +/- 789.38) microg/(mL x min). Linear Regression and Confidence Interval analyses suggested a linear kinetic characteristic. Doripenem was mainly excreted through kidneys, with 24 h cumulative urine excretion rates ranging from 70% to 75% for the three doses of infusions. It was safe to administer doripenem through infusion in healthy volunteers. Adverse reactions occurred in 19.44% cases of infusions, although all were mild reactions. Tinnitus happened in two cases (8.33%) of infusions, which required close observations. CONCLUSION: Doripenem infusion possesses a linear kinetics. There is no need to adjust the regimenpatients.