Mechanism of Action of Bimatoprost, Latanoprost, and Travoprost in Healthy Subjects: A Crossover Study
Received 4 December 2006; received in revised form 29 June 2007; accepted 2 July 2007.
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.
1Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota.
2Department of Ophthalmology, St. Thomas' Hospital, London, United Kingdom.
3Division of Biostatistics, Mayo Clinic, Rochester, Minnesota.
4Department of Ophthalmology, University of Nebraska Medical Center, Omaha, Nebraska.
Correspondence to Jay W. McLaren, PhD, Mayo Clinic, 200 First Street SW, Rochester, MN 55905.
Manuscript no. 2006-1388.
Supported in part by unrestricted grants from Allergan Inc., Irvine, California; Alcon Ltd., Fort Worth, Texas; Research to Prevent Blindness, Inc., New York, New York; National Institutes of Health, Bethesda, Maryland (grant no. EY 07065); and Mayo Foundation, Rochester, Minnesota. Dr Lim is an International Glaucoma Association (United Kingdom) fellow and has received an unrestricted travel grant from Pfizer Inc. (UK).
ABSTRACT