Pharmacokinetics and metabolism of anecortave acetate in animals and humans.

Abstract The ocular delivery of anecortave acetate was tested in preclinical and clinical pharmacokinetic and metabolism studies. Results of initial studies led to the design of a new cannula that could effectively deliver anecortave acetate as a posterior juxtascleral depot, providing adequate retinal and choroidal drug concentrations for up to 6 months after a single administration. A counter-pressure device was designed to prevent drug reflux during and immediately after posterior juxtascleral depot administration. Pharmacokinetic studies support the effectiveness of these devices. Anecortave acetate is rapidly hydrolyzed by esterases to pharmacologically active anecortave desacetate, and is further reductively metabolized to one major and several minor products that circulate as glucuronide conjugates. Low levels of these anecortave acetate metabolites were detectable for only approximately 2 weeks in the plasma after a 15-mg posterior juxtascleral depot administration to age-related macular degeneration patients. Studies show that posterior juxtascleral depot administration of anecortave acetate is an effective, minimally invasive method of delivering this drug to the choroid and retina.