Des-enkephalin-gamma-endorphin: bioavailability in rats following the subcutaneous and intramuscular route of administration.
A pharmacokinetic study with [3H]des-enkephalin-gamma-endorphin (3H-DE gamma E) was performed in rats after the intravenous, subcutaneous and intramuscular route of administration. Disappearance of non-metabolized 3H-DE gamma E from blood upon intravenous dosing followed a biphasic decay with half-lives of 0.7 +/- 0.3 (+/- S.D.) min for the initial distribution phase and 6.3 +/- 2.7 min for the terminal elimination phase. The central and peripheral volumes of distribution were strikingly high (0.38 and 0.55 1 X kg-1, respectively). Extensive metabolism occurred already within the first minutes after injection. The blood clearance rate was found to be 0.29 +/- 0.12 1 X min-1 X kg-1, which value points to remarkable extrahepatic elimination of the neuropeptide. As compared to the intravenous route of administration, subcutaneous or intramuscular injection of 3H-DE gamma E resulted in low but longer-lasting peptide levels in blood. These levels reached already peak values at 2 min after both routes of administration and then declined to below the limit of detection at 2-3 h. The absolute bioavailability of DE gamma E after subcutaneous injection amounted to 30.9 +/- 16.3% (range 16.0-46.9%), whereas the bioavailability after intramuscular injection was observed to be 3.5 times lower (8.5 +/- 3.0%; range 4.6-12.0%). These data suggest that subcutaneous dosing of DE gamma E might be more effective in displaying CNS activity than the intramuscular route.
D000818:Animals; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D004723:Endorphins / Q000008:administration & dosage / Q000378:metabolism*; D006207:Half-Life; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate; D051381:Rats; D011919:Rats, Inbred Strains; D001615:beta-Endorphin
D004723:Endorphins; D001615:beta-Endorphin; C033558:des-enkephalin-gamma-endorphin