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Abstract
13,14-Dihydro-17-phenyl-18,19,20-trinor-PGF2α-isopropyl ester (latanoprost) is a new prostaglandin drug developed for the treatment
of glaucoma. In clinical trials a daily dose of 1.5 μg is effective in reducing the
intraocular pressure. In toxicological studies doses from 2 μg/eye to 100 μg/eye have
been used in various species. This paper reports the development and validation of
a radioimmunoassay of latanoprost acid (PhXA85) and its application to toxicokinetic
studies performed in monkeys. An antiserum was raised in rabbits by immunization with
PhXA85 coupled to BSA at the carboxylic acid by the mixed anhydride method. The antibody
titre was found to be about 1:2000 to 1:3000. The cross-reactivity with 13,14-dihydro-15(R,S)-17-phenyl-trinor-PGF2α, 13,14-dihydro-15(S)-17-phenyl-trinor-PGF2α, dinor-PhXA85, 17-phenyl-trinor-PGF2α, latanoprost and PGF2α was 46.4, 4.2, 7.6, 2.2, 0.1 and 0.039%, respectively. The intra-assay precision
was between ± 7.7 and 11.7% (CV) at the level of 320 pg/ml and ±8.3 and 9.7% with
1280 pg/ml in plasma samples from man, monkey, rat and aqueous humour from human and
rabbit. Similarly, the intra-assay accuracy varied between 95.9 and 102.5% and 89.0
and 109.0% for the low and high standards, respectively. The inter-assay precision
and accuracy were between ±6.0 and 13.4% and 91.0 and 92.8% in the monkey plasma samples.
The limit of detection was 3 pg/tube or 30 pg/ml. In a long-term study, the acid of
latanoprost was rapidly cleared from plasma in monkeys treated with eye drops of latanoprost
(2 × 3 μg/day) over a period of 1 year.
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Article info
Publication history
Accepted:
May 15,
1996
Received:
April 26,
1996
Identification
Copyright
© 1996 Published by Elsevier Inc.
