Effects of PhXA41, A New Prostaglandin F Analog, on Aqueous Humor Dynamics in Human Eyes

Carol B Toris, C. B. Camras, M. E. Yablonski

Research output: Contribution to journalArticle

381 Citations (Scopus)

Abstract

Purpose: PhXA41, a new phenyl-substituted analog of a prostaglandin F (PGF) prodrug (13,14-dihydro-17-phenyl-18,19,20-trinor-prostagland in F-1-isopropyl ester), is an effective ocular hypotensive agent in patients with glaucoma. To understand its mechanism of action, various components of aqueous humor dynamics were examined after topical application to human eyes. Methods: In a randomized, double-masked, placebo-controlled study, PhXA41 (0.006%) was given topically twice daily for 1 week to one eye each of 22 volunteers with normotension or ocular hypertension. The other eye was similarly treated with vehicle. Intraocular pressure (IOP) was measured by pneumatonometry and tonographic outflow facility by pneumatonography. Aqueous flow and outflow facility were determined either directly or indirectly by a fluorophotometric technique, and uveoscleral outflow was calculated secondarily. Comparison of values obtained in treated versus contralateral control eyes and on baseline versus day 8 of treatment were made. Results: Compared with baseline measurements, PhXA41 significantly (P < 0.001) reduced IOP by 5.5 ± 0.6 mmHg (mean ± standard error of the mean) as measured 3 hours after the last dose on the eighth day of treatment. Aqueous flow, tonographic outflow facility, and fluorophotometric outflow facility were not changed by PhXA41. However, uveoscleral outflow was significantly greater in the PhXA41-treated eyes (0.87 + 0.22 µl/minute) compared with either the contralateral vehicle-treated eyes (0.14 ± 0.30; P < 0.02) or baseline measurements (0.39 ± 0.20 µl/minute; P < 0.05). Conclusions: PhXA41 decreases IOP in humans by increasing uveoscleral outflow without significantly affecting other parameters of aqueous humor dynamics.

Original languageEnglish (US)
Pages (from-to)1297-1304
Number of pages8
JournalOphthalmology
Volume100
Issue number9
DOIs
StatePublished - Jan 1 1993

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Synthetic Prostaglandins
Dinoprost
Aqueous Humor
Intraocular Pressure
Ocular Hypertension
Prodrugs
Proxy
Glaucoma
Volunteers
Esters
Placebos
Therapeutics

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Effects of PhXA41, A New Prostaglandin F Analog, on Aqueous Humor Dynamics in Human Eyes. / Toris, Carol B; Camras, C. B.; Yablonski, M. E.

In: Ophthalmology, Vol. 100, No. 9, 01.01.1993, p. 1297-1304.

Research output: Contribution to journalArticle

Toris, Carol B ; Camras, C. B. ; Yablonski, M. E. / Effects of PhXA41, A New Prostaglandin F Analog, on Aqueous Humor Dynamics in Human Eyes. In: Ophthalmology. 1993 ; Vol. 100, No. 9. pp. 1297-1304.
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abstract = "Purpose: PhXA41, a new phenyl-substituted analog of a prostaglandin F2α (PGF2α) prodrug (13,14-dihydro-17-phenyl-18,19,20-trinor-prostagland in F2α-1-isopropyl ester), is an effective ocular hypotensive agent in patients with glaucoma. To understand its mechanism of action, various components of aqueous humor dynamics were examined after topical application to human eyes. Methods: In a randomized, double-masked, placebo-controlled study, PhXA41 (0.006{\%}) was given topically twice daily for 1 week to one eye each of 22 volunteers with normotension or ocular hypertension. The other eye was similarly treated with vehicle. Intraocular pressure (IOP) was measured by pneumatonometry and tonographic outflow facility by pneumatonography. Aqueous flow and outflow facility were determined either directly or indirectly by a fluorophotometric technique, and uveoscleral outflow was calculated secondarily. Comparison of values obtained in treated versus contralateral control eyes and on baseline versus day 8 of treatment were made. Results: Compared with baseline measurements, PhXA41 significantly (P < 0.001) reduced IOP by 5.5 ± 0.6 mmHg (mean ± standard error of the mean) as measured 3 hours after the last dose on the eighth day of treatment. Aqueous flow, tonographic outflow facility, and fluorophotometric outflow facility were not changed by PhXA41. However, uveoscleral outflow was significantly greater in the PhXA41-treated eyes (0.87 + 0.22 µl/minute) compared with either the contralateral vehicle-treated eyes (0.14 ± 0.30; P < 0.02) or baseline measurements (0.39 ± 0.20 µl/minute; P < 0.05). Conclusions: PhXA41 decreases IOP in humans by increasing uveoscleral outflow without significantly affecting other parameters of aqueous humor dynamics.",
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