Toxicity and Safety Profile of Latanoprost: Ocular, Systemic, and Reproductive Effects
Multiple animal studies have assessed the toxicity of latanoprost, a prostaglandin F2α analog used in glaucoma therapy, both ocularly and systemically. Overall, research shows that latanoprost is extremely well tolerated, with a wide safety margin. In fact, the systemic hazardous dose is over a thousand times greater than the usual clinical eye dose.
Systemic Toxicology Findings
In non-anesthetized monkeys, an intravenous injection of high-dose latanoprost (approximately 100 times the clinical dose per kg body weight) increased respiration rate. This result could reflect temporary bronchoconstriction. Animal investigations showed no sensitization or allergic symptoms.
Ocular Toxicology and Eye Safety
In both rabbits and monkeys, no ocular damage occurred at dosages of 100 mcg/eye/day when compared to the clinical dose of 1.5 mcg/eye/day.
However, investigations have revealed unique ocular-related effects.
- Monkeys' iris pigmentation increased.
This is thought to be the outcome of iris melanocytes being stimulated to produce melanin.
Importantly, no proliferative or detrimental cellular alterations were seen.
The pigment change may be permanent.
- Blepharoplasty (eyelid tissue alterations) occurred at a dose of 6 mcg/eye/day, which is substantially higher than clinical values.
These effects were reversible and had not been observed in people at conventional therapeutic levels.
Mutagenicity and carcinogenicity
Latanoprost has an excellent safety profile in genetic toxicity studies:
Negative outcomes:
- Bacterial Mutation Reversal Test
- Mouse lymphoma gene mutation test
- Mouse micronucleus test.
Human lymphocytes exhibited chromosome aberrations in vitro, similar to the reaction documented with natural prostaglandin F2α. This shows that it could be a class-related effect, not specific to latanoprost.
Additional research, including irregular DNA synthesis assays in rats (both in vivo and in vitro), revealed no mutagenic activity.
Carcinogenicity investigations in mice and rats were negative, showing no cancer-causing potential.
Effects on fertility and reproduction
Animal experiments have revealed:
- There is no impact on male or female fertility.
- In rats, intravenous dosages of 5, 50, and 250 μg/kg/day showed no embryotoxicity.
- In rabbits, dosages of 5 μg/kg/day or above resulted in embryo mortality and substantial fetal toxicity, including:
-Increased late absorption.
-Higher rates of miscarriage.
-Reduced fetal weight
Notably, no teratogenic effects (birth abnormalities) were detected in any species.