Abstract
Latanoprost (13,14-dihydro-17-phenyl-18,19,20-trinor-prostaglandin F2α-1-isopropyl ester) is a unique prostaglandin analogue developed for the treatment of glaucoma. To investigate the pharmacokinetics, tritium-labeled latanoprost was administered topically on the eyes of rabbits and intravenously. About 7.7% of the applied dose was found in the cornea at 15 min after the drug administration. The following Cmaxand elimination half-life (interval 1–6 hr) values of the total radioactivity in the eye tissues were found: aqueous humor, 0.09 ng eq/ml and 3.0 hr; anterior sclera, 1.49 ng eq/mg and 1.8 hr; cornea, 1.59 ng eq/mg and 1.8 hr; ciliary body, 0.39 ng eq/mg and 2.8 hr; conjunctiva, 1.41 ng eq/mg and 1.4 hr; and iris, 0.39 ng eq/mg and 2.1 hr. Latanoprost was rapidly hydrolyzed, and most of the radioactivity found in the aqueous humor, anterior eye tissues, and plasma corresponded to the pharmacologically active acid of latanoprost. The initial plasma elimination half-life of the acid of latanoprost was 9.2 ± 3.2 min after iv and 2.3 ± 1.9 min after topical administration on the eyes. The plasma clearance of the acid of latanoprost was 1.8 ± 0.3 liters/hr·kg, and the volume of distribution was 0.4 ± 0.1 liter/kg after iv administration. Based on the retention times on HPLC and GC-MS, the main metabolite in urine and feces was identified as the 1,2,3,4-tetranor metabolite of acid of latanoprost. This acid existed in equilibration with the corresponding δ-lactone. The AUC of radioactivity in the eye tissues was approximately 1000 times higher than in plasma AUC. The recovery of radioactivity was complete.
Footnotes
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Send reprint requests to: Birgitta Sjöquist, Essinge Högväg 34, S-11265 Stockholm, Sweden.
- Abbreviations used are::
- IOP
- intraocular pressure
- PGF2α
- prostaglandin F2α
- Received August 28, 1997.
- Accepted March 10, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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