Enantiomeric analysis of terfenadine in rat plasma by HPLC.

Enantiomeric pairs of the antihistaminic drug terfenadine and its carboxylic acid derivative were directly separated by HPLC using an ovomucoid protein column. Absolute configurations of terfenadine enantiomers were assigned by comparing their circular dichroism spectra with those of 1-phenyl-1-butanol enantiomers of known absolute stereochemistry. Terfenadine and its major carboxylic acid metabolite extracted from blood plasma following an oral administration of a racemic terfenadine to rats were found to be enriched in the (S)- and (R)-enantiomers, respectively. The results indicated that the (R)-enantiomer of an orally administered racemic terfenadine was preferentially oxidized in rats to form a carboxylic acid metabolite enriched in the (R)-enantiomer.     

Effects of chronic infusion of dibutyryl c-AMP or adenosine on luteal function in sheep

Adenosine or vehicle; dibutyryl c-AMP, a c-AMP analogue, or vehicle in two separate experiments were infused through an indwelling cannula every four hours around the ovarian vascular pedicle of ewes unilaterally ovariectomized on day 8 postestrus. Adenosine or vehicle was infused from day 8 through 22 postestrus and dibutyryl-cAMP was infused from day 8 through 20 postestrus or until the ewes returned to estrus. Interestrous intervals were greater (p less than or equal to 0.05) in ewes receiving adenosine (27.3 +/- 2.4 days) than in control ewes (17.2 +/- 1.3 days). The length of the estrous cycle of ewes receiving dibutyryl c-AMP was greater (22.4 +/- 1.1; p less than or equal to 0.05) than in control ewes which averaged 16.7 +/- 0.6 days. Profiles of progesterone were different (p less than or equal to 0.05) for ewes receiving adenosine or dibutyryl c-AMP when compared to their respective controls. In addition, the overall mean concentrations of progesterone were greater (p less than or equal to 0.05) in dibutyryl c-AMP or adenosine-treated ewes than in controls. In a third experiment, infusions of adenosine or dibutyryl c-AMP intrauterine every 4 hours through a cannula from day 8 through 22 postestrus had no effect (p less than or equal to 0.05) on the interestrous interval or profiles of progesterone. It is concluded that dibutyryl c-AMP or adenosine in vivo can delay luteolysis and adenosine and c-AMP may play roles in luteal secretion of progesterone in sheep but are probably not the uterine embryonic antiluteolysin of early pregnancy in sheep.     

Prostaglandins F in uterine and ovarian compartments and in plasma from the uterine vein, ovarian artery and vein, and abdominal aorta of pseudopregnant rats with and without deciduomata

Prostaglandins F were measured in uterine and ovarian compartments and in uterine venous, ovarian arterial and venous and abdominal aorta plasma and the uptake of ³H-PGF_2α by ovarian compartments of 240 pseudopregnant rats with or without bilateral deciduomata in five experiments. Concentrations of PGF in deciduomal tissue, uterine venous plasma, ovarian arterial and venous plasma, corpora lutea, and remainder of the ovary and ³H-PGF_2α in the ovary were consistently as high or higher in pseudopregnant rats with deciduomata as in the endometrium, ovarian compartments, or samples of plasma from the same blood vessels of pseudopregnant rats without deciduomata jtLevels of PGF were consistently 3 to 7 fold higher in uterine venous than in plasma from the abdominal aorta. It is concluded that extended luteal maintenance by deciduomal tissue is by some mechanism other than an inhibition of PGF synthesis by the uterus, transfer of PGF locally to the ovary, or uptake of PGF by the ovarian compartments.