Establishment of an In Vitro–In Vivo Correlation for Melanin Binding and the Extension of the Ocular Half-Life of Small-Molecule Drugs

A large variety of drugs bind effectively to melanin, and this binding influences their ocular pharmacokinetic and distribution profiles. We aimed to establish a correlation between in vitro melanin binding and in vivo ocular pharmacokinetics (PK). The extent of melanin binding in vitro was determined for a set of model drugs; binding kinetics and binding isotherms were generated and fitted to a mechanistic model to derive the drug–melanin...