Mechanism of Action of Bimatoprost, Latanoprost, and Travoprost in Healthy Subjects. A Crossover Study

K. Sheng Lim, Cherie B. Nau, Megan M. O'Byrne, David O. Hodge, Carol B Toris, Jay W. McLaren, Douglas H. Johnson

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Abstract

Purpose: To study the effects of 3 prostaglandin analogs, bimatoprost, latanoprost, and travoprost, on aqueous dynamics in the same subjects and to compare techniques of assessing outflow facility. Design: Experimental study (double-masked, placebo-controlled, randomized paired comparison, 4-period crossover). Participants: Thirty healthy adult subjects. Methods: Bimatoprost, latanoprost, travoprost, or a placebo was administered to the left eye once a day in the evening for 7 days, after a minimum 4-week washout period between each session. Tonographic outflow facility was measured by Schiøtz tonography and pneumatonography on day 7. On day 8, the aqueous humor flow rate and fluorophotometric outflow facility were measured by fluorophotometry. Uveoscleral outflow was calculated from the aqueous humor flow rate and outflow facility using the Goldmann equation. Main Outcome Measures: Facility of outflow, aqueous humor flow rate, intraocular pressure (IOP), and calculation of uveoscleral outflow. Results: All medications lowered IOP relative to a placebo. None of the drugs affected aqueous humor production. All medications increased outflow facility compared with placebo when measured by Schiøtz and 2-minute pneumatonography (P≤0.02); the apparent increase of outflow facility measured with fluorophotometry and 4-minute pneumatonography did not reach statistical significance. In contrast, uveoscleral outflow was significantly increased by all medications when calculated from 4-minute pneumatonography data, and fluorophotometry and Schiøtz data at higher episcleral venous pressures. The apparent increase found with 2-minute pneumatonography did not reach statistical significance. These differing results in the same patients indicate that differences in measurement techniques, and not differences in mechanism of action, explain previous conflicting published reports on the mechanism of action of the prostaglandins. Conclusions: Bimatoprost, latanoprost, and travoprost have similar mechanisms of action. All 3 drugs reduce IOP without significantly affecting the aqueous production rate. All drugs increase aqueous humor outflow, either by enhancing the pressure-sensitive (presumed trabecular) outflow pathway or by increasing the pressure-insensitive (uveoscleral) outflow, but the assessment of the amount of flow through each pathway depends upon the measurement technique.

Original languageEnglish (US)
Pages (from-to)790-795.e4
JournalOphthalmology
Volume115
Issue number5
DOIs
StatePublished - May 2008

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latanoprost
Aqueous Humor
Cross-Over Studies
Fluorophotometry
Healthy Volunteers
Intraocular Pressure
Placebos
Pharmaceutical Preparations
Synthetic Prostaglandins
Pressure
Matched-Pair Analysis
Venous Pressure
Double-Blind Method
Prostaglandins
Research Design
Outcome Assessment (Health Care)
Bimatoprost
Travoprost

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Lim, K. S., Nau, C. B., O'Byrne, M. M., Hodge, D. O., Toris, C. B., McLaren, J. W., & Johnson, D. H. (2008). Mechanism of Action of Bimatoprost, Latanoprost, and Travoprost in Healthy Subjects. A Crossover Study. Ophthalmology, 115(5), 790-795.e4. https://doi.org/10.1016/j.ophtha.2007.07.002

Mechanism of Action of Bimatoprost, Latanoprost, and Travoprost in Healthy Subjects. A Crossover Study. / Lim, K. Sheng; Nau, Cherie B.; O'Byrne, Megan M.; Hodge, David O.; Toris, Carol B; McLaren, Jay W.; Johnson, Douglas H.

In: Ophthalmology, Vol. 115, No. 5, 05.2008, p. 790-795.e4.

Research output: Contribution to journalArticle

Lim, K. Sheng ; Nau, Cherie B. ; O'Byrne, Megan M. ; Hodge, David O. ; Toris, Carol B ; McLaren, Jay W. ; Johnson, Douglas H. / Mechanism of Action of Bimatoprost, Latanoprost, and Travoprost in Healthy Subjects. A Crossover Study. In: Ophthalmology. 2008 ; Vol. 115, No. 5. pp. 790-795.e4.
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AU - O'Byrne, Megan M.

AU - Hodge, David O.

AU - Toris, Carol B

AU - McLaren, Jay W.

AU - Johnson, Douglas H.

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N2 - Purpose: To study the effects of 3 prostaglandin analogs, bimatoprost, latanoprost, and travoprost, on aqueous dynamics in the same subjects and to compare techniques of assessing outflow facility. Design: Experimental study (double-masked, placebo-controlled, randomized paired comparison, 4-period crossover). Participants: Thirty healthy adult subjects. Methods: Bimatoprost, latanoprost, travoprost, or a placebo was administered to the left eye once a day in the evening for 7 days, after a minimum 4-week washout period between each session. Tonographic outflow facility was measured by Schiøtz tonography and pneumatonography on day 7. On day 8, the aqueous humor flow rate and fluorophotometric outflow facility were measured by fluorophotometry. Uveoscleral outflow was calculated from the aqueous humor flow rate and outflow facility using the Goldmann equation. Main Outcome Measures: Facility of outflow, aqueous humor flow rate, intraocular pressure (IOP), and calculation of uveoscleral outflow. Results: All medications lowered IOP relative to a placebo. None of the drugs affected aqueous humor production. All medications increased outflow facility compared with placebo when measured by Schiøtz and 2-minute pneumatonography (P≤0.02); the apparent increase of outflow facility measured with fluorophotometry and 4-minute pneumatonography did not reach statistical significance. In contrast, uveoscleral outflow was significantly increased by all medications when calculated from 4-minute pneumatonography data, and fluorophotometry and Schiøtz data at higher episcleral venous pressures. The apparent increase found with 2-minute pneumatonography did not reach statistical significance. These differing results in the same patients indicate that differences in measurement techniques, and not differences in mechanism of action, explain previous conflicting published reports on the mechanism of action of the prostaglandins. Conclusions: Bimatoprost, latanoprost, and travoprost have similar mechanisms of action. All 3 drugs reduce IOP without significantly affecting the aqueous production rate. All drugs increase aqueous humor outflow, either by enhancing the pressure-sensitive (presumed trabecular) outflow pathway or by increasing the pressure-insensitive (uveoscleral) outflow, but the assessment of the amount of flow through each pathway depends upon the measurement technique.

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