Plasma Clearance and Plasma Half-Disappearance Time of Exogenous Thyrotropin-Releasing Hormone and Pyroglutamyl-N^3im-Methyl-Histidyl Prolineamide*

Abstract

The plasma clearance rate (PCR) and plasma half-disappearance time (t1/2) of TRH was compared to the PCR and t1/2 of pyroglutamyl-N3im-methyl-histidyl prolineamide (methyl-TRH), a more potent analog of TRH in normal subjects. The PCR for TRH was 1500 +/- 329 (SD) ml/min, which was significantly greater than the PCR of methyl-TRH (783 +/- 96 ml/min). The t1/2 of TRH was 6.2 min compared to a t1/2 of 11.5 min for methyl-TRH. The slower clearance of methyl-TRH is probably due to the increased resistance to degradation by serum enzymes of methyl-TRH compared to TRH.

Changes in plasma thyrotrophin-releasing hormone, thyrotrophin, prolactin and thyroid hormone levels after intravenous, intranasal or rectal administration of synthetic thyrotrophin-releasing hormone in man

“…The findings obtained by iv administration confirmed those of previous reports (Anderson et al 1971;Hollander et al 1972;Bassiri & Utiger 1973;Hershman 1974;Morely et al 1979). The mean plasma TRH concentrations were 6.2-12.0 pg/ml before TRH administration and differed from previous reports (Lombardi et al 1978;Guignier et al 1981).…”

“…There are many reports related to the effects of iv administration of synthetic thyrotrophin-releasing hormone (TRH) on thyrotrophin (TSH), prolactin and thyroid hormone release in man, and changes in plasma TRH concentration after iv administra¬ tion (Anderson et al 1971;Hollander et al 1972;Bassiri & Utiger 1973;Hershman 1974;Morely et al 1979). The effect of the route of administration on hormone release and plasma TRH concentra¬ tions however, has rarely been studied (Schäfgen et al 1983).…”

Immunoreactive thyrotrophin-releasing hormone like material (IR-TRH LM) in human cord blood: high circulating serum levels but possible non-identity with hypothalamic TRH

“…In the present as well in the previously reported TRH-RIA's (Leppäluoto 1976;Spindel & Wurtman 1980), only TRH analogues differing from L pyroglu-L his-L pro NH2 by substitution or altera¬ tion of the histidyl residue seem susceptible to interfere significantly with the assay and it should be mentioned that such changes in the TRH mole¬ cule can interfere with serum degradation without necessarily abolishing bioactivity (Morley et al 1979). …”

TRH pharmacokinetics and nerve stimulation evoked prostatic fluid secretion during TRH infusion in the dog

“…This suggests little tissue binding of TRH and rapid elimination. We have previously deter¬ mined TRH pharmacokinetics in the rat using a constant infusion method (Safran et al 1984) and TRH pharmacokinetics have also been deter¬ mined in humans (Morley et al 1979;Bassiri & Utiger 1973) and sheep (Klindt et al 1979). Table 3 summarizes data from these studies with the various species listed in order of their weight.…”

“…The pharmacokinetics of TRH have been deter¬ mined in the rat (Safran et al 1984;Jackson et al 1979), in humans (Bassiri & Utiger 1973; Leppaluoto et al 1972;Morley et al 1979), and in sheep (Klindt et al 1979). The plasma or serum of all of these species contains enzyme(s) that rapidly de¬ grade TRH (Emerson 1986) and the relatively short half-time of TRH after iv injection has been at¬ tributed to the presence of plasma TRH degrading activity (Jackson et al 1979;Bassiri & Utiger 1973).…”