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Hayette Rebika, Laure Chauchat, Thierry Amar, Karen Viaud-Quentric, Camille Guerin; A comparative pharmacokinetics study of 3 Latanoprost eyedrops solutions containing various excipients in an animal model. Invest. Ophthalmol. Vis. Sci. 2022;63(7):4166 – F0158.
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© ARVO (1962-2015); The Authors (2016-present)
Benzalkonium chloride (BAC), the most common preservative used in anti-glaucoma eyedrops, has been described in the literature as increasing prostaglandin corneal penetration but to date, this fact seems to be controversial. In addition, surfactants may play a role in lipophilic agent solubilization and could, therefore, influence active substance (AS) penetration. The purpose of the study was to evaluate the role of formulation on the AS bioavailability by assessing the pharmacokinetics (PK) profile of different latanoprost eyedrops solutions on a rabbit model.
3 different formulations of 0.005% Latanoprost were tested: A. preservative-free (PF) and surfactant-free (SF) formulation; B. same SF formulation but containing BAC 0.02%; and C. different PF formulation but containing Macrogolglycerol hydroxystearate 40 (MGHS 40) at 5%. The ocular concentration of Latanoprost free acid (LAT) was monitored according to GLP standards in 3 parallel groups of Dutch Belted rabbit following a single ocular administration of each tested items in the right eye (n=6). Aqueous humor (AH) and iris-ciliary body (ICB) samples were collected at the following timepoints: 0.5h, 1h, 2h, 3h, 4h, 8h, 24h post-dose. LAT concentrations were measured by RRLC-MS/MS validated method; statistical analysis (Fisher LSD) was performed. PK parameters (AUC, Cmax, Tmax, t1/2) were calculated.
In both AH and ICB, the concentration of LAT was statistically not different for A and B at each timepoint, except for t1h in ICB (p=0.005). However, LAT behavior in C was statistically inferior to A and B in AH and ICB from t30min to t3h (p<0.05). In terms of AUC, A (521 ng/mL.h; 300 ng/g.h) and B (470 ng/mL.h; 269 ng/g.h) were at least 2 times higher than C (210 ng/mL.h; 97 ng/g.h) in both AH and ICB respectively. Cmax follow the same ratio for A and B vs C. Tmax was 2h in AH and between 0.5 to 1h in ICB.
The absence or presence of BAC within the formulations A and B did not influence the PK profile as a similar behavior in LAT concentrations is described all over the study duration. Therefore, BAC for penetration purposes is no longer justified. However, these in vivo PK results highlighted the importance of formulation as a significantly lower absorption in AH and ICB is measured for the C formulation. This may be due to the presence of MGHS 40 which could be a matter of questioning.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.
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