Comparison of Efficacy and Safety Evaluation of Latanoprost Formulations with and without Benzalkonium Chloride

Hiroyoshi Kasai, Yumiko Aoyama, Takashi Kurasawa, Tomoyo Imamura, Kazuhiro Tsuruma, Hideaki Hara, Haruhisa Hirata, Tetsuya Yamamoto

Department of Ophthalmology, Gifu University Graduate School of Medicine, Gifu, Japan.
Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan.
Research and Development, Wakamoto Pharmaceutical Co., Ltd., Tokyo, Japan.
Sagami Research Laboratories, Wakamoto Pharmaceutical Co., Ltd., Kanagawa, Japan.

DOI: 10.4236/pp.2013.44054                

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.

Keywords

Latanoprost; NP; Benzalkonium; Benzalkonium-Free; Bioequivalence

Conflicts of Interest

The authors declare no conflicts of interest.

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