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Progesterone Pharmacokinetics in the Mouse: Implications for Potential Stroke Therapy

Progesterone Pharmacokinetics in the Mouse: Implications for Potential Stroke Therapy

Raymond Wong, David Ray, David A Kendall

J Pharm Pharmacol. 2012 Nov;64(11):1614-20.

PMID: 23058048

Abstract:

Objectives:
Progesterone has been shown to be neuroprotective in a number of preclinical central nervous system injury models including cerebral ischaemia. The aim of this study was to clarify differences in outcomes owing to different dosing regimens and the pharmacokinetic profile of progesterone, particularly in relation to brain levels.
Methods:
Male C57 Bl/6 mice were injected intraperitoneally with progesterone (8 mg/kg in dimethylsulfoxide) or with a bolus injection followed by continuous subcutaneous infusion (1.0 µl/h of a 50 mg/ml progesterone solution) via implanted osmotic minipumps. Plasma and brain samples were collected over 24 h from bolus-injected mice and 48 h from mice implanted with minipumps. Progesterone concentrations were measured by an enzyme-linked immunoassay and pharmacokinetic profiles were constructed.
Key findings:
Intraperitoneally injected progesterone had a short half-life (fast component half-life of 0.2 h) in both plasma and brain. Minipump delivery resulted in higher concentrations of progesterone in plasma and particularly in brain over a longer period. The volume of distribution with intraperitoneal injection was 172.78 versus 1641.84 ng/h per g via minipump in the first 24 h.
Conclusions:
A bolus intraperitoneal loading dose of progesterone followed by continuous delivery via osmotic minipump is an effective way of delivering progesterone to the brain.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP57830-A	Progesterone solution		57-83-0	Price

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