Ocular topotecan pharmacokinetics following topical administration to rabbits for diffused anterior retinoblastoma.
J Pharm Pharmacol
; 69(5): 574-581, 2017 May.
Article
em En
| MEDLINE
| ID: mdl-27578324
ABSTRACT
OBJECTIVES:
We characterized and compared the in-vivo absorption of topotecan into the aqueous humor after instillation of aqueous and ointment formulations.METHODS:
A lanolin/petrolatum ointment was used. New Zealand rabbits were instilled with topotecan solution (6 µg, group A), a single 10 µg dose of topotecan ointment (group B) or with five 10 µg doses of topotecan ointment (group C). Aqueous humor samples were collected at different times. Corneal samples were collected only for group A. Topotecan was quantified using HPLC, and pharmacokinetic parameters were calculated. Acute corneal epithelial toxicity was assessed after multiple instillations of topotecan ointment. KEYFINDINGS:
Total topotecan maximum aqueous humor concentration (Cmax ) was 16.1, 69.9 and 287 ng/ml in group A, B and C, respectively. A single dose of topotecan ointment increased threefold and sevenfold the aqueous humor Cmax , and exposure compared to the aqueous formulation. Aqueous humor concentrations from group C eyes were substantially above the cytotoxic concentration for retinoblastoma cells. No corneal toxicity was evident after ointment instillation.CONCLUSIONS:
Topotecan penetrated into the aqueous humor of the rabbit eye after multiple doses of an ointment in concentrations pharmacologically active against retinoblastoma cells without eliciting acute toxicity. Topotecan ointment may translate to the clinical treatment of anterior segment disseminated retinoblastoma.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Soluções Oftálmicas
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Retinoblastoma
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Corpo Vítreo
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Topotecan
Limite:
Animals
Idioma:
En
Revista:
J Pharm Pharmacol
Ano de publicação:
2017
Tipo de documento:
Article