Impact of ring size and drug loading on the pharmacokinetics of a combination dapivirine-darunavir vaginal ring in cynomolgus macaques.
Int J Pharm
; 550(1-2): 300-308, 2018 Oct 25.
Article
en En
| MEDLINE
| ID: mdl-30153490
ABSTRACT
This work investigates the impact of vaginal ring size and drug loading on the in vitro release, safety, ease of fit, and pharmacokinetics in cynomolgus macaques of matrix-type silicone elastomer vaginal rings containing a combination of the non-nucleoside reverse transcriptase inhibitor dapivirine and the protease inhibitor darunavir. Drug-free and drug-loaded vaginal rings having three different geometries were manufactured by reaction injection molding. In vitro drug release was assessed using both a solvent/water mixture and a vaginal fluid simulant. Macaques fitted with drug-free vaginal rings for 28â¯days were assessed by colposcopy, cytological evaluation of cervico-vaginal lavage and histological evaluation of tissue after ring removal. The 20â¯×â¯4.5â¯mm combination ring, deemed most appropriate for vaginal fit and comfort in the macaques, was evaluated for pharmacokinetics over 28â¯days. Substantial differences were observed in the in vitro release profiles between the three ring sizes. However, these differences were not manifest in vivo, where measured drug concentrations after 20â¯×â¯4.5â¯mm ring use were not significantly different from those reported previously with a 25â¯×â¯6â¯mm ring. These results suggest that ring placement and fit is an important species-specific study parameter that should be optimised prior to pharmacokinetic testing.
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Bases de datos:
MEDLINE
Asunto principal:
Pirimidinas
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Dispositivos Anticonceptivos Femeninos
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Fármacos Anti-VIH
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Darunavir
Límite:
Animals
Idioma:
En
Revista:
Int J Pharm
Año:
2018
Tipo del documento:
Article