Pharmacokinetics and tolerability of a novel progesterone intravaginal ring in sheep.
Drug Deliv Transl Res
; 9(5): 1008-1016, 2019 10.
Article
in En
| MEDLINE
| ID: mdl-31066007
ABSTRACT
The objectives of this work were to evaluate the in vitro release and in vivo pharmacokinetics and local tolerability of a novel, segmented ethylene-vinyl acetate (EVA) intravaginal ring (IVR) delivering progesterone (P) in drug-naïve ovariectomized female Dorset crossbred sheep. Following preparation and assessment of in vitro release of P, animals were randomized into one of six treatment groups group 1 Crinone® 8% gel (90 mg); group 2 Prometrium® 200-mg capsules; group 3 placebo IVR; group 4 progesterone (P) IVR 4 mg/day; group 5 P IVR 8 mg/day; or group 6 P IVR 12 mg/day. Crinone 8% gel and Prometrium capsules were administered once daily for 28 days. IVRs were inserted vaginally on day 1 and remained in place through day 14; a new ring was administered on day 15 and was removed at day 28. Animals underwent daily examinations to confirm ring placement, and vaginal irritation was scored from 0 (none) to 4 (severe). Blood samples were taken at scheduled times for pharmacokinetic analysis. Postmortem examinations performed on all IVR groups included vaginal irritation, macroscopic, and microscopic evaluations, including irritation scoring and histopathology. Intravaginal rings were retained over 28 days in all animals. Clinical observations showed no significant abnormal findings in any group. Pharmacokinetic analysis in animals showed sustained release of P over from days 0 through 14 of ring use. Irritation scores and microscopic assessments were consistent with the IVRs being well tolerated. These results will guide future human clinical studies to ultimately develop an IVR for use in women for the prevention of preterm birth.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Progesterone
/
Drug Delivery Systems
/
Contraceptive Devices, Female
Limits:
Animals
Language:
En
Journal:
Drug Deliv Transl Res
Year:
2019
Document type:
Article
Affiliation country:
Publication country:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
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EUA
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UNITED STATES
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UNITED STATES OF AMERICA
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US
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USA