Document Detail

Ocular and systemic pharmacokinetics of latanoprost in humans.
MedLine Citation:
PMID:  12204697     Owner:  NLM     Status:  MEDLINE    
The ocular pharmacokinetics of latanoprost (13,14-dihydro-17-phenyl-18, 19,20-trinor-PGF(2alpha)-isopropyl ester; Xalatan [Pharmacia-Upjohn, Peapack, NJ]) was studied in patients undergoing cataract surgery using radio-immunoassay, and the systemic pharmacokinetics of latanoprost was studied in healthy human volunteers with 3H-latanoprost as well as radioimmunoassay. After topical application, latanoprost was rapidly hydrolysed in the cornea and blood. The maximum concentration of the active drug, latanoprost acid, was detected in the aqueous humor 1-2 hours after topical administration of the clinical dose and amounted to 15-30 ng/ml. The half-life of latanoprost acid in the aqueous humor was 2-3 hours. In the systemic circulation the peak concentration of latanoprost acid appeared 5 minutes after topical application and reached a level of 53 pg/ml with an elimination half-life of 17 minutes. In patients that had been on the drug continuously for more than 1 year, 5 out of 10 had plasma levels of latanoprost acid below the limit of detection (<30 pg/ml). The mean plasma clearance was 0.40 +/- 0.04 l/h. kg, and the volume of distribution was 0.16 +/- 0.02 l/kg after intravenous administration. The corresponding figures after ocular administration were 0.88 l/h. kg, and 0.36 l/kg. The majority of the radioactivity was recovered in urine (88%) and the rest was found in feces. In the eye the main metabolism of latanoprost was the ester hydrolysis. The only prominent chromatographic peak in plasma corresponded to latanoprost acid. In urine no latanoprost or latanoprost acid was detected. Before excretion latanoprost acid was beta oxidized to 1,2-dinor and 1,2,3,4-tetranor latanoprost acid. These metabolites accounted for approximately 66% of the radioactivity in urine. In conclusion, latanoprost is rapidly hydrolyzed in the eye and blood to latanoprost acid. Minimal further metabolism occurs in the eye, but latanoprost acid undergoes beta oxidation and other metabolism outside the eye. After topical application the peak concentration in aqueous humor was approximately 10(-7) M, whereas that in plasma was about 10(-10) M or less.
Birgitta Sjöquist; Johan Stjernschantz
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Survey of ophthalmology     Volume:  47 Suppl 1     ISSN:  0039-6257     ISO Abbreviation:  Surv Ophthalmol     Publication Date:  2002 Aug 
Date Detail:
Created Date:  2002-09-02     Completed Date:  2002-12-20     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  0404551     Medline TA:  Surv Ophthalmol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  S6-12     Citation Subset:  IM    
Department of Neuroscience, Unit of Pharmacology, Uppsala University, SE-751 24 Uppsala, Sweden.
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MeSH Terms
Administration, Topical
Antihypertensive Agents / pharmacokinetics*
Aqueous Humor / metabolism*
Chromatography, High Pressure Liquid
Infusions, Intravenous
Intraocular Pressure / drug effects
Prostaglandins F, Synthetic / pharmacokinetics*
Reg. No./Substance:
0/Antihypertensive Agents; 0/Prostaglandins F, Synthetic; 130209-82-4/latanoprost

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