Evaluation of In Vitro Metabolism- and Transporter-Based Drug Interactions with Sunscreen Active Ingredients

Area of Science:

• Pharmacology and Toxicology
• Dermatology
• Drug Metabolism and Transport

Background:

• Sunscreen active ingredients are widely used for UV protection.
• Potential interactions between sunscreen ingredients and co-administered drugs are a concern.
• Understanding the impact of sunscreen on drug metabolism and transport is crucial for consumer safety.

Purpose of the Study:

• To evaluate the in vitro inhibitory potential of six sunscreen active ingredients on cytochrome P450 (CYP) enzymes.
• To assess the impact of these sunscreen ingredients on the function of key drug uptake transporters.
• To determine if sunscreen ingredients interfere with drug metabolism and transport processes.

Main Methods:

• In vitro metabolism assays using human liver microsomes for CYP2C9, CYP2D6, and CYP3A4.
• In vitro uptake transporter assays using transfected cell lines for OAT3, OCT2, and OATP1B1.
• Evaluation of avobenzone, enzacamene, oxybenzone, octinoxate, trolamine, and homosalate up to their solubility limits.

Main Results:

• Enzacamene, oxybenzone, and trolamine showed inhibition of CYP2C9 activity, with IC50 values exceeding clinical plasma levels.
• No significant inhibition of CYP2D6 or CYP3A4 was observed for any tested sunscreen ingredients.
• Oxybenzone and trolamine inhibited OAT3 and OCT2 transporters, but IC50 values were higher than clinical plasma concentrations.

Conclusions:

• In vitro inhibition of CYP2C9 and renal transporters by some sunscreen ingredients was observed.
• The measured IC50 values for inhibition exceeded the total plasma levels found in clinical studies.
• It is unlikely that these sunscreen active ingredients will inhibit drug metabolism or transport in consumers using sunscreen products.