Pharmacokinetics and pharmacodynamics of TRH during pregnancy

To determine the pharmacokinetics and pharmacodynamics of thyrotropin-releasing hormone (TRH) in pregnant women.

Twenty-four pregnant and eight nonpregnant women were given 400 micrograms TRH as either intravenous infusion or bolus. Serial venous samples were collected for TRH, TSH, thyroxine, and prolactin assay.

When given as bolus, mean (+/- standard error of the mean) peak plasma concentration (50 +/- 5.2 and 73 +/- 5.1 ng/mL, P < .01), elimination half life (4.3 +/- 0.3 and 6.3 +/- 0.4 minutes, P < .001), and area under the curve (156.4 +/- 14.8 and 340.1 +/- 32.8 ng/mL/minute, P < .001) in pregnant subjects were reduced compared with controls, whereas plasma clearance (45.4 +/- 6.5 and 23.6 +/- 2.1 mL/kg/minute, P < .01) and volume of distribution (27.8 +/- 1.8 and 19.0 +/- 1.3% body weight, P < .01) were increased. When given by infusion, steady-state concentration (6.6 +/- 0.5 and 9.8 +/- 0.9 ng/mL, P < .01) and elimination half-life (4.6 +/- 0.5 and 6.3 +/- 0.3 minutes, P < .05) were lower in pregnant subjects than in controls. Thyrotropin-releasing hormone kinetics were independent of mode of administration. Although basal TSH and thyroid hormone concentrations were similar in patients and controls, the TSH response to TRH was blunted in pregnant subjects compared with controls (9.3 +/- 0.6 and 16.4 +/- 1.4 microIU/mL, P < .001). The basal (3187 +/- 488 and 147 +/- 16 mIU/L) and maximal prolactin response (6193 +/- 426 and 1316 +/- 106 mIU/L) were increased in pregnant subjects compared with controls (P < .001).

The peak plasma concentration and elimination half-life of TRH are reduced during pregnancy because of the increased volume of distribution and rapid clearance. Mode of administration does not affect TRH pharmacokinetics, but the maternal pharmacodynamic response differs in patients receiving bolus compared with infusion.