[Pharmacokinetics study of injected doripenemin healthy volunteers].

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.