The pharmacokinetics of thyrotropin-releasing hormone (TRH) and deamido-TRH in the rat.
The pharmacokinetics of TRH and its metabolite deamido-TRH (TRH-OH) were evaluated and compared. After a 60- to 90-min infusion of the appropriate peptide into rats, the MCR, half-life of disappearance (t 1/2), and volume of distribution were calculated. The MCR of TRH averaged 4 ml/min, whereas that of TRH-OH was 6.5 ml/min. The serum concentrations of both TRH and TRH-OH decreased in a biexponential manner after stopping the corresponding peptide infusions. The t 1/2 values were 2.4 and 3.9 min for the initial phase of disappearance and 14.1 and 20.6 min for the later phase of disappearance for TRH and TRH-OH, respectively. The volume of distribution of TRH-OH was twice that of TRH. The fractional conversion rate of TRH to TRH-OH, based on serum TRH-OH concentrations measured during TRH infusions, was 0.7-1.4%. Less than 1 ng TRH-OH was excreted in the urine during the last 30 min of TRH infusion. The rapid clearance of TRH-OH and low fractional conversion of TRH to TRH-OH, as measured in serum, suggest that little TRH secretion will be reflected in serum TRH-OH concentrations.
D000818:Animals; D006207:Half-Life; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000378:metabolism*
C020271:thyrotropin-releasing hormone, deamido-; D013973:Thyrotropin-Releasing Hormone; D011761:Pyrrolidonecarboxylic Acid