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Absorption, Excretion and Tissue Residue in Feedlot Heifers Injected with the Synthetic Prostaglandin, Fenprostalene

Syntex Research, Palo Alto, CA 94304

¹ To whom correspondence should be addressed at Syntex Research, 3401 Hillview Avenue, Palo Alto, CA.

Abstract

Preliminary studies on use of the synthetic prostaglandin, fenprostalene, as an abortifacient had indicated that maximum effectiveness was dependent upon slow delivery. Because both route of administration and formulation control delivery rates, the influences of intramuscular (im) vs subcutaneous (sc) injections, and aqueous acetate buffer (AAB) vs polyethylene glycol-400 (PEG) vehicles on the plasma concentration and urinary excretion of fenprostalene were compared. Feedlot heifers were administered 1 mg injections of [13,14-³H]-fenprostalene. Blood samples and total urine excretion were collected during the following 96 h. The maximum concentration of tritium in plasma occurred at 2 h for AAB-im (.90 ng eq/ml), PEG-im (.75 ng eq/ml) and AAB-sc (.64 ng eq/ml), and then declined throughout 24 h with t values of 6.1, 9.4 and 9.2 h, respectively. The peak concentration from PEG-sc was lower (.37 ng eq/ml, P<.05), observed later (4h, P<.05) and declined more slowly following peak concentration (t = 15.1 h, P<.05). Consistent with delayed absorption, a smaller fraction (P<.05) of the total radioactivity excreted in urine was recovered during the first 24 h after injection for PEG-sc (85%) than for PEG-im (95%), AAB-sc (97%) or AAB-im (99%). In a tissue distribution study, plasma, urine and fecal samples were collected and heifers were slaughtered at various times following sc injection of 1 mg of [³H] fenprostalene in PEG. Peak concentrations of tritium in plasma occurred between 4 and 8 h and declined with a t of 15.2 h. Urine contained 60% and feces 40% of total recovered radioactivity. Drug equivalent concentrations in edible tissues 24 h after injection were .74, 2.25, .09 and .15 ppb in liver, kidney, muscle and fat, respectively, and continued to decline. Formulation of fenprostalene in PEG for sc injection resulted in a sustained-release prostaglandin. Nonetheless, the compound was rapidly excreted in urine and feces, leaving no persistent tissue residue.

² The authors thank Bonita Bowers, Judy Haller and Jose Rosetefor assistance with the in-life portions, and Carolyn Ackley, Larry Bowen and Steven Smith for assistance with the laboratory portions of these studies.