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G.M. Comer, T.A. Ciulla, C. Peloquin, J. Wheeler; Human Vitreous Distribution of Linezolid After a Single Oral Dose . Invest. Ophthalmol. Vis. Sci. 2004;45(13):506.
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Purpose: The authors undertook a pharmacokinetics pilot study to evaluate the relationship between vitreous linezolid concentrations verses both time and serum concentrations after a single 600 mg oral dose. Methods: Eleven adult patients with macular pucker or macular hole undergoing pars plana vitrectomy were given a single oral dose of 600 mg linezolid prior to surgery. Each then received a pre– and post–vitrectomy blood draw and vitrectomy for the vitreous specimen. The samples were immediately shipped to an outside facility for concentration analysis using HPLC. Results: The patients were divided into two groups: one group (n=5) underwent vitrectomy before the mean time of maximum serum linezolid concentration as stated on the linezolid package insert (i.e. Tmax = 77 minutes after oral linezolid administration) and the second group (n=6) underwent vitrectomy after the time of maximum serum concentration. In the early group (mean time 52 minutes), the mean linezolid concentrations measured 2.67 mcg/ml in the serum prior to vitrectomy and 0.06 mcg/ml in the vitreous. In the later group (mean time 139 minutes), the mean concentration measured 11.30 mcg/ml in the serum prior to vitrectomy and 1.25 mcg/ml in the vitreous. The serum linezolid concentrations pre–vitrectomy (r=0.77, p<0.01) and post–vitrectomy (r=0.69, p<0.01) showed a strong correlation with time, while vitreous concentrations tended to demonstrate a positive correlation with time (r=0.46), but did not achieve statistical significance (0.05<p<0.10). However, the vitreous linezolid concentrations had a strong correlation with the extrapolated serum linezolid concentrations (r=0.70,p<0.01) at the time of vitrectomy. Conclusions: This study suggests that vitreous linezolid concentrations increase with increased serum concentrations which increase with time after ingestion. Because the mean inhibitory concentrations (MIC) of the aerobic Gram–positive cocci range between 2–4 mcg/ml, adequate serum levels were frequently reached by the Tmax with a single oral 600 mg linezolid dose. Although the mean vitreous concentration failed to reach an adequate MIC after a single oral dose, it is possible that multiple oral doses to achieve steady state would result in higher vitreous levels at times later than those studied here. In addition, it is likely that eyes with inflammation would show break down of the blood retinal barrier with higher linezolid penetration. Further study is warranted.
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