Pranoprofen

To explore the effect of the variation of pupil diameter (PD) and intraocular pressure (IOP) induced by femtosecond laser treatment on the subsequent phacoemulsfication and intraocular lens implantation. And whether the application of 0.1% pranoprofen could significantly reduce the miosis and increased IOP caused by femtosecond laser treatment in femtosecond laser-assisted cataract surgery (FLACS).

In this study, patients were pretreated with (trial group) or without (control group) topical 0.1% pranoprofen. The PD and IOP were measured at different time points within 30 ​min after the completion of the femtosecond laser treatment.

The comparisons of the two groups showed the PD of patients pretreated with 0.1% pranoprofen was significantly larger than that of the control only at 15 ​min after FLACS (P ​= ​0.046), and there was no significant difference in IOP at any time point (P ​> ​0.05). Neither the ratio of significant miosis (PD ​≤ ​5 ​mm) nor intraocular hypertension (IOP ≥30 ​mmHg) was significantly different between the control group (1.72%, 6.67%) and the trial group (1%, 4.17%) (P ​> ​0.05).

The PD and IOP of patients undergoing FLACS showed fluctuations within a small range. The rates of significant miosis and intraocular hypertension are very low, it is safe for surgeons to complete the follow-up procedures within 30 ​min after femtosecond laser treatment. Pretreatment with 0.1% pranoprofen exerted a slight, albeit significant prophylactic effect preventing pupil miosis. However, it provided only a limited benefit in patients undergoing FLACS without other complications.

Cytochrome P450 4A11 (CYP4A11) has many endogenous and exogenous compounds containing a carboxyl group in their structure as substrates. If drugs with this characteristic potently attenuate the catalytic function of CYP4A11, drug-drug interactions may occur. Acidic non-steroidal anti-inflammatory drugs (NSAIDs) possess a carboxylic acid in their structure. However, it remains unclear whether these drugs inhibit CYP4A11 activity. The present study examined the inhibitory effects of acidic NSAIDs on CYP4A11 activity using human liver microsomes (HLMs) and recombinant CYP4A11. Sulindac sulfide, ibuprofen, and flurbiprofen effectively decreased the luciferin-4A O-demethylase activity of HLMs and recombinant CYP4A11 (inhibition rates of 30-96% at an inhibitor concentration of 100 μM), while salicylic acid, aspirin, diclofenac, mefenamic acid, indomethacin, etodolac, ketoprofen, loxoprofen, S-naproxen, pranoprofen, zaltoprofen, and oxaprozin exhibited weaker inhibitory activity (inhibition rates up to 23%). Among the drugs tested, sulindac sulfide was the most potent inhibitor of CYP4A11 activity. A kinetic analysis of the inhibition of CYP4A11 by sulindac sulfide revealed mixed-type inhibition for HLMs (K_i = 3.38 μM) and recombinant CYP4A11 (K_i = 4.19 μM). Sulindac sulfide is a pharmacologically active metabolite of sulindac (sulfoxide form), which is also oxidized to sulindac sulfone. To elucidate the role of a sulfur atom of sulindac sulfide in the inhibition of CYP4A11, the inhibitory effects of sulindac sulfide and its oxidized forms on CYP4A11 activity were examined. The potency of inhibition against HLMs was greater in the order of sulindac sulfide, sulindac, and sulindac sulfone; IC₅₀ values were 6.16, 52.7, and 71.6 μM, respectively. The present results indicate that sulindac sulfide is a potent inhibitor of CYP4A11. These results and the molecular modeling of CYP4A11 with sulindac sulfide and its oxidized forms suggest that a sulfur atom of sulindac sulfide as well as its carboxylic acid play important roles in the inhibition of CYP4A11.