TITLE:
Comparison of Efficacy and Safety Evaluation of Latanoprost Formulations with and without Benzalkonium Chloride
AUTHORS:
Hiroyoshi Kasai, Yumiko Aoyama, Takashi Kurasawa, Tomoyo Imamura, Kazuhiro Tsuruma, Hideaki Hara, Haruhisa Hirata, Tetsuya Yamamoto
KEYWORDS:
Latanoprost; NP; Benzalkonium; Benzalkonium-Free; Bioequivalence
JOURNAL NAME:
Pharmacology & Pharmacy,
Vol.4 No.4,
July
1,
2013
ABSTRACT:
Background: This study
investigated the safety (cytotoxicity in
vitro) and pharmacological effects (ocular hypotensive effects and aqueous
humor concentrations in normotensive monkeys in vivo) of latanoprost formulations with benzalkonium chloride (latanoprost with BAK) and without
BAK (NP). Methods: A bioequivalence
study of latanoprost with BAK and NP was also conducted on human healthy
volunteers. Cytotoxicity and the protective effect against H2O2 stress in vitro were evaluated using
human corneal epithelial cells. The ocular hypotensive effects in normotensive
monkeys were measured by pneumatonometer and the aqueous humor concentrations
of latanoprost free acid were determined by
liquid chromatography/mass spectrum (LC/MS) methods. The bioequivalence study of
latanoprost with BAK and NP was carried out as a single eye drop, two-sequence,
crossover randomized study. Results: Cytotoxicity tests in vitro revealed
that NP was less toxic than latanoprost with BAK and significantly inhibited H2O2 induced cell damage while latanoprost with BAK did not. The hypotensive
efficacy and the latanoprost free acid concentrations in aqueous humor of each
formulation were not significantly different in monkeys. In the bioequivalence
study, NP was bioequivalent to latanoprost with BAK. NP was safer than
latanoprost with BAK with respect the results obtained in the in vitro cytotoxicity test. There was no
difference observed between latanoprost with BAK and NP in the IOP lowering
effect in monkeys and healthy volunteers. Conclusion: Taken together, these results indicate that NP is as effective as latanoprost
with BAK, and is more likely to maintain ocular surface health than latanoprost
with BAK.