PHARMACOKINETICS OF OFLOXACIN IN SERUM AND VITREOUS-HUMOR OF ALBINO AND PIGMENTED RABBITS

The purpose of this study was to evaluate the pharmacokinetics of oflo xacin in serum and vitreous humor samples from albino and pigmented ra bbits by using a recently described animal model which permits robust estimation of parameter values. The drug was administered to rabbits i ntravenously, multiple vitreous humor and serum samples were taken fro m each rabbit, and the vitreous humor and serum samples were assayed b y high-pressure liquid chromatography. The pharmacokinetic parameters were determined with RSTRIP, an iterative, nonlinear, weighted, least- squares regression program. Eight New Zealand White rabbits and eight Dutch Belted rabbits (split into single-dose and multiple-dose groups) were investigated in this study. The value of penetration into the vi treous humor of albino rabbits (n = 6) was 32.6% +/- 2.12%, with termi nal-elimination half-life values of 3.21 and 2.39 h, respectively, for vitreous humor and serum. In pigmented rabbits after a single dose (n = 3) and with a steady-state concentration of drug in serum (n = 4), penetration values were similar, at 30.4% +/- 2.98% and 30.0% +/- 4.12 %, respectively (P > 0.10). Following a single dose of ofloxacin, pigm ented animals had elimination half-life values from serum and vitreous humor of 2.64 and 4.32 h, respectively. After steady state was achiev ed, half-life values for serum and vitreous humor were 3.12 and 6.05 h , respectively. By comparing pigmentation, dose mode, and elimination from vitreous humor, the vitreous humor half-life value for singly dos ed albino rabbits (3.21 h) was not more rapid than that for singly dos ed pigmented rabbits (4.32 h [P > 0.10]) but was more rapid than that for multiply dosed pigmented rabbits (6.05 h [P < 0.05]). The excellen t penetration of ofloxacin into uninflamed rabbit eyes in conjunction with the higher levels in blood found in humans and greater activity a gainst coagulase-negative staphylococci suggest that ofloxacin may be preferable to other quinolones for evaluation in the prophylaxis and t reatment of bacterial endophthalmitis.