Effect of Combined Exposure to EDTA and Zinc Pyrithione on Pyrithione Absorption in Rats

Zinc pyrithione (ZnPT) is a coordination complex of zinc and has been used widely as an anti-dandruff agent in shampoos. Many shampoos contain both ZnPT and EDTA, a chelating agent speculated to increase ZnPT absorption, thereby raising concerns about neurotoxicity. Here, we investigated the effect of EDTA on ZnPT absorption by direct comparison of ZnPT and pyrithione (PT) concentrations in shampoo formulations, and by pharmacokinetic analysis of ZnPT, PT, and 2-methanesulfonylpyridine (MSP), the main ZnPT metabolite, in rat plasma or urine following exposure to shampoo containing ZnPT alone or a combination of ZnPT and EDTA. Approximately 17.3% of ZnPT was converted to PT by the addition of EDTA in the shampoo formulation. Plasma ZnPT and PT concentrations were not measured up to 24 hr after treatment with shampoo containing 1% ZnPT or 1% ZnPT + 2% EDTA in all rats. However, PT amount in 24-hr urine sample, MSP concentration in plasma, and MSP amount in 24-hr urine sample were approximately 4-, 2.6-, and 2.7-fold higher, respectively, in the 1% ZnPT + 2% EDTA shampoo group than in the 1% ZnPT shampoo group. As confirmed by the formulation analysis and in vivo pharmacokinetic analysis, the exposure of ZnPT could be increased by the absorption of PT due to partial dissociation of ZnPT into PT.