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Endocrinology, doi:10.1210/endo-115-3-1031
Endocrinology Vol. 115, No. 3 1031-1037
Copyright © 1984 by the Endocrine Society.
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The Pharmacokinetics of Thyrotropin-Releasing Hormone (TRH) and Deamido-TRH in the Rat*

MARJORIE SAFRAN, CHIH-FANG WU, RICHARD MATYS, SHARON ALEX and CHARLES H. EMERSON

Division of Endocrinology and Metabolism, Department of Medicine, University of Massachusetts Medical School Worcester, Massachusetts 01605

Address requests for reprints to: Dr. Charles H. Emerson, Division of Endocrinology and Metabolism, University of Massachusetts Medical School, Worcester, Massachusetts 01605.

Abstract

The pharmacokinetics of TRH and its metabo-lite 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 (t1/2), 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 biex-ponential manner after stopping the corresponding peptide infusions. The t1/2 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. (Endocrinology 115: 1031–1037, 1984)

Footnotes

* This work was supported by Research Grants AM-27850 and AM-07302 from the NIADDK, NIH (Bethesda, MD).

Received February 10, 1984.






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Copyright © 1984 by The Endocrine Society