Pharmacokinetics and effects of 17 beta-estradiol and progesterone implants in ovariectomized rats

Mannino, Christy A., South, Samantha M., Inturris, Charles E. and Quinones-Jenab, Vanya (2005) Pharmacokinetics and effects of 17 beta-estradiol and progesterone implants in ovariectomized rats. Journal of Pain, 6 12: 809-816. doi:10.1016/j.jpain.2005.07.007

Author Mannino, Christy A.
South, Samantha M.
Inturris, Charles E.
Quinones-Jenab, Vanya
Title Pharmacokinetics and effects of 17 beta-estradiol and progesterone implants in ovariectomized rats
Journal name Journal of Pain   Check publisher's open access policy
ISSN 1526-5900
Publication date 2005-12
Sub-type Article (original research)
DOI 10.1016/j.jpain.2005.07.007
Volume 6
Issue 12
Start page 809
End page 816
Total pages 8
Place of publication Edinburgh, Scotland
Publisher Churchill Livingstone
Language eng
Subject 1115 Pharmacology and Pharmaceutical Sciences
Abstract For the pharmacokinetic evaluation of Silastic capsules, ovariectornized (OVX) rats were implanted subcutaneously with this dosage form containing 17 beta-estradiol (5, 10, 15, or 20% in cholesterol, where 5% 17 beta-estradiol equals 0.4 mg) or progesterone (20, 40, 110, or 220 mg of crystalline progesterone). The time-course of serum 17 beta-estradiol and progesterone released from these capsules in the OVX rat is characterized by an initial increase in serum hormone levels followed by a decline and then an apparent steady-state that persists from 7 to 24 days postimplant. Both hormones have large clearance values (total clearance is 97.7 L/day for 17 beta-estradiol and 20.9 L/clay for progesterone). For 17 beta-estradiol and progesterone only, 11% of the dose was released from the implant after 24 days. Thus, the Silastic membrane represents the rate controlling barrier for these hormones. The relationship between graded doses of 17 beta-estradiol or progesterone and serum concentration was linear. Neither tail flick latencies measured at 48, 52.5, and 55 degrees C nor the antinociceptive potency of morphine (ED50 values) were altered by continuous administration to steady-state of graded doses of 17 beta-estradiol or progesterone. We demonstrate how a dose-dependent analysis of some of the behavioral effects of 17 beta-estradiol or progesterone can be conducted at steady-state serum hormone concentrations. Perspective: we describe a method to obtain sustained serum levels of estrogen or progesterone and the consequences of these sustained hormone levels on acute thermal nociception and the antinociceptive response to morphine. This rat model of hormone replacement may provide insights into the role of these hormones in pathological pain states.
Keyword Clinical Neurology
Ovariectomized rat
17 beta-estradiol
Silastic implant
Tail flick latency
Morphine ED50
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
ERA 2012 Admin Only
School of Pharmacy Publications
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Citation counts: TR Web of Science Citation Count  Cited 40 times in Thomson Reuters Web of Science Article | Citations
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Created: Fri, 25 Jan 2008, 16:44:13 EST