Safety and pharmacokinetics of a preservative-free triamcinolone acetonide formulation for intravitreal administration.

摘要

PURPOSE: The safety and pharmacokinetics of a triamcinolone acetonide (TA) preservative-free (TA-PF) formulation were investigated after intravitreal administration in rabbits. METHODS: A TA-PF formulation was prepared as a sterile 40-mg/mL or 160-mg/mL suspension in single-use vials by adding TA powder to 0.5% hydroxypropyl methylcellulose in normal saline. TA-PF (4-mg and 16-mg doses) and Kenalog (Bristol-Myers-Squibb, Princeton, NJ) (4-mg dose) were injected into the vitreous of separate groups of rabbits, and drug levels were measured in the vitreous over time with HPLC. Ocular toxicology (clinical examination, serial electroretinography, and histopathologic analysis) was evaluated in a separate group of animals after intravitreal TA-PF injection. RESULTS: The half-lives of the injection amount in the vitreous, 4-mg TA-PF, 16-mg TA-PF, and 4-mg Kenalog, were found to be 24 days, 39 days, and 23 days, respectively. There were no signs of toxicities by clinical examination after TA-PF injection. Serial electroretinograms of rabbits receiving either 4-mg or 16-mg intravitreal TA-PF injections remained normal over time. Histopathologic analysis showed normal ocular tissues in animals receiving either 4-mg or 16-mg intravitreal TA-PF injections. CONCLUSION: The half-life of TA in the vitreous after a 4-mg injection of either TA-PF or Kenalog was comparable. A 16-mg dose of TA-PF produced a long vitreous half-life, and this may be of clinical benefit in patients requiring 6 months of drug exposure in the eye for a chronic disease.