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  • Title: Absorption and penetration of dinoprost (prostaglandin F2 alpha) and dinoprost methyl ester into perfused mesenteric circulation in rats.
    Author: Taylor BM, Sun FF.
    Journal: J Pharm Sci; 1979 Aug; 68(8):983-6. PubMed ID: 480179.
    Abstract:
    The absorption of dinoprost (prostaglandin F2 alpha) and its methyl ester in rat jejunum was studied. A 22-cm segment of rat jejunum was cannulated at both ends and connected to an oscillating perfusion pump system. The mesenteric vasculature supplying this isolated segment also was cannulated and perfused with Kreb's bicarbonate buffer with dextran. Solutions of 3H-dinoprost or its methyl ester were introduced into the lumen and oscillated through the segment. The disappearance of radioactivity from the lumen and the appearance of radioactivity in the vascular perfusate were monitored. The metabolite patterns in the vascular perfusate were analyzed by TLC. A lag between the time the drug disappeared from the lumen and the time it appeared in the mesenteric circulation was detected. This lag was longer for the methyl ester than for the free acid, even though the ester disappears from the lumen faster than does the free acid. Upon removal of dinoprost from the gut lumen, a gradual decrease in the amount of drug appearing in the mesenteric circulation could be detected. However, with the ester, a slight increase could be observed for approximately 0.5 hr, followed by a decrease. Metabolism by the gut wall appears to be greater for the ester than for the acid. The results suggest that, although the ester disappears from the lumen more quickly than does the acid, it actually penetrates to the blood at a slower rate and undergoes greater metabolism.
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