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DD Tang-Liu, M Cherukury, A Acheampong, J Cheetham, A VanDenburgh, D Yu; Systemic Pharmacokinetics of Bimatoprost 0.03% Solution Following Once Daily Ocular Dosing In Normal, Healthy Subjects . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1085.
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Purpose: To determine the pharmacokinetic profile of bimatoprost and its potential C-1 acid metabolite (17-phenyltrinor PGF2α) in 15 healthy subjects. Method: Every subject received one drop of bimatoprost 0.03% solution to each eye once daily for 14 days. Serial blood samples were collected on Days 1, 7, and 14 for the measurement of blood bimatoprost and the potential C-1 acid metabolite concentration using a validated LC-MS/MS method at the lower limits of quantitation (LLOQ) of 0.025 ng/mL and 0.05 ng/mL, respectively. Results: The potential C-1 acid metabolite was not detected in blood in any of the 14 completed subjects. Bimatoprost appeared rapidly in the blood and the mean tmax ranged from 6.3 to 7.9 min on different collection days (i.e., days 1, 7, and 14). The mean bimatoprost Cmax values on days 1, 7, and 14 were 0.0864, 0.0721, and 0.0822 ng/mL, respectively. The mean Cmax and tmax values were similar on different collection days. After reaching maximum levels, blood concentrations of bimatoprost rapidly declined and were below 0.025 ng/mL within 1 to 1.5 hours of dosing in all but one subject. In this subject, blood bimatoprost concentration was below LLOQ within 3 hours of dosing. Estimation of the half-life was not uniformly performed for all subjects on day 1 due to insufficient data in calculating the apparent elimination rate constant. The mean bimatoprost AUC0-t values on days 1, 7, and 14 were 0.0318, 0.0259, and 0.0444 ng•hr/mL, respectively. These values indicated that there was no systemic accumulation of bimatoprost following the daily ocular administration for 14 days. Conclusion: There was no detection of the potential C-1 acid metabolite from ocular administration of bimatoprost, indicating it is not a prodrug. Bimatoprost is absorbed and eliminated quickly from the systemic circulation following ocular dosing to human subjects. No drug accumulation was noted following multiple dosing.
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