PubMed · 5703380
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C Keeler. Note on olfacto-genes.. https://doi.org/10.1093/oxfordjournals.jhered.a107692
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The purpose of this study was to evaluate the pharmacokinetics of ofloxacin in serum and vitreous humor samples from albino and pigmented rabbits by using a recently described animal model which permits robust estimation of parameter values. The drug was administered to rabbits intravenously, multiple vitreous humor and serum samples were taken from each rabbit, and the vitreous humor and serum samples were assayed by 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 vitreous humor of albino rabbits (n = 6) was 32.6% +/- 2.12%, with terminal-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, pigmented animals had elimination half-life values from serum and vitreous humor of 2.64 and 4.32 h, respectively. After steady state was achieved, half-life values for serum and vitreous humor were 3.12 and 6.05 h, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
PURPOSE: This study was designed to investigate the possibility that gentamicin-induced retinal toxicity is dependent on ocular pigmentation by comparing the effects of the drug on the functional and morphologic integrity of the retina in albino and pigmented rabbits. METHODS: In each rabbit, a solution of gentamicin sulfate was injected into the vitreous of one eye, and saline was injected into the other eye. Retinal function was assessed by electroretinogram (ERG) at different time intervals after injection. Retinal structure was examined at the light microscopic level. RESULTS: In albino and pigmented rabbits, functional retinal damage developed to a maximal level within the first week after gentamicin injection. Thereafter, gradual recovery could be seen in eyes that suffered less than 80% maximal reduction in the ERG b-wave. For each dose >0.1 mg studied, retinal damage was more severe in the albino rabbits than in the pigmented ones. The degree of damage was not affected by the level of ambient illumination, nor was it reduced by the administration of N-acetylcystein, a free radical scavenger, together with gentamicin. CONCLUSIONS: Ocular pigmentation partially protects the rabbit retina from the toxic action of gentamicin. This protection probably reflects binding of the drug by the melanin, which thereby reduces the concentration of the free gentamicin. When the initial gentamicin-induced retinal damage is expressed in < 80% reduction in the ERG, substantial recovery may occur in both strains of rabbits.