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ARVO 2024: Understanding the pharmacokinetics of latanoprost and prednisolone acetate with perfluorohexyloctane

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The rabbit model found that the levels of the active metabolites were very comparable, whether or not eyes had received a prior installation of perfluorohexyloctane.

Megan Cavet, PhD, sat down with Emily Kaiser Maharjan of Optometry Times to discuss her 2024 ARVO poster, "Effects of perfluorohexyloctane on the ocular pharmacokinetics of latanoprost and prednisolone acetate after topical administration to rabbits." The study investigated the effects of the long-lasting monolayer created by perfluorohexyloctane and whether the order of administration affected the absorption of active ingredients.

Video transcript

Editor's note: This transcript has been lightly edited for clarity.

Emily Kaiser Maharjan:
Hi everyone. I'm here with Megan Cavet lead investigator on a poster that's being presented at ARVO. So thank you so much for taking the time to chat today. I'm really excited to learn more about this research.

Megan Cavet, PhD:
Thanks. I'm happy to talk about it. So yes, this ARVO poster presents findings from a rabbit ocular pharmacokinetic study evaluating the effect of perfloruohexyloctane, or brand name Miebo, on the absorption of other topically instilled ocular medications.

So just a bit of background about perfluorohexyloctane. It was FDA approved last year for the treatment of the signs and symptoms of dry eye disease. And it's a very unique therapy. So it's the first and only prescription eye drop that directly targets tear evaporation. That's a major contributor to the dry eye disease, continuing cycle of the disease. So perfluorohexyloctane differs from other dry eye disease prescription medications in that it's 100% active. So the perfluorohexyloctane is at 100% There is no vehicle in the formulation. And so it's an aqueous-free formulation, and it doesn't require a preservative. So it has a number of unique physical chemical properties, which give rise to its mechanism of action. So it's got a very low surface tension, and it spreads rapidly and evenly across the ocular surface. And it has a very unique structure. And it's amphiphilic. This enables it to form a monolayer, a long-lasting monolayer, across the across the tear film on top of the tear film. And because of this monolayer formation, it can inhibit the evaporation of the underlying aqueous layer of the tear film. And in this way, it can improve the tear film homeostasis and improve the signs and symptoms of dry eye disease.

So we wanted to perform this study, this was a rabbit pharmacokinetic study, to see whether because perflourohexyloctane forms this long-lasting monolayer, could it impact the absorption of other topically applied medications if a patient were to instill it prior to their other medications?

So we performed a study in the rabbits where the rabbits were divided into 2 groups, and the rabbits were instilled with latanoprost ophthalmic solution alone or following a topical installation of perfluorohexyloctane, which was applied 15 minutes earlier. And then the second group of rabbits received prednisolone acetate ophthalmic suspension, again either alone or 15 minutes after receiving a single installation of perfluorohexyloctane.

Because perfluorohexyloctane forms a monolayer on the ocular surface, we wanted to determine if a patient were to instill their other topical medications after their perfluorohexyloctane, would the absorption of those drugs be impacted by the layer of perfluorohexyloctane? So we performed a study in rabbits were the eyes were instilled with latanoprost ophthalmic solution alone, or 15 minutes following a single installation of perfluorohexyloctane and another group of rabbits receive prednisolone acetate ophthalmic suspension alone or 15 minutes following a single installation of perfluorohexyloctane. So the levels of the the active metabolites, latanoprost acid and prednisolone, were evaluated in the ocular tissues of the rabbits over between 5 minutes and 4 hours following installation. So the ocular tissues that were evaluated with a cornea conjunctiva aqueous humor and the iris ciliary body. And the main findings were that the levels of the active metabolites were very comparable, whether or not the rabbits had received a prior installation of perfluorohexyloctane or not.

Kaiser Maharjan:
Can you tell me some of the key takeaways that you really want to drive home to eye care professionals?

Cavet:
Yes, of course. So the key takeaway of the study really is that in this rabbit model, prior installation of perfluorohexyloctane did not impact the absorption of the other applied topically ophthalmic drops, so the latanoprost solution and the prednisolone acetate suspension. So this suggests that if a patient were on multiple medications were to install their perfluorohexyloctane prior to their other medications, there would be no impact on the penetration or efficacy of those other medications. However, if an eye care professional were to prescribe multiple medications for a patient, then because Miebo forms this long-lasting monolayer on the ocular surface, it may be good to consider to counsel the patient to actually instill that aqueous eye drops first prior to instilling perfluorohexyloctane.

Kaiser Maharjan:
Yeah, that's a super helpful little tidbit. So thanks for mentioning that. Do you have any plans to further this research?

Cavet:
So I think the data is clear on the impact of perfluorohexyloctane installation prior to other medications. In the future, we may look at ways in which we could evaluate whether other aqueous drops may impact the monolayer formation of perfluorohexyloctane. So this is a bit harder to do, of course, because the active is perfluorohexyloctane and there's no active metabolites that can be directly measured, but that's something that we may look at in the future.

Kaiser Maharjan:
Thank you so much for taking the time to chat today. The study is absolutely fascinating, and I really appreciate your commentary.
You're welcome. Thank you for having me.

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