Estimated rate of XXXX secretion into the circulation of normal humans.

@entity2871 @entity57393 @entity117 @entity7489 @entity3448
We have measured the excretion of a major urinary metabolite of @entity7489 ( @entity3448 ), i.e., @entity57393 , during the infusion of exogenous @entity3448 over a 50-fold dose range to enable estimation of the rate entry of endogenous @entity3448 into the bloodstream. Four healthy male volunteers received 6-h i.v. infusions of venhicle alone and @entity3448 at 0.1, 1.0, and 5.0 ng/kg X min in random order. They were pretreated with @entity117 at a dose of 325 mg/d in order to suppress endogenous @entity3448 production. Urinary @entity57393 was measured before, during, and up to 24 h after the infusions and in @entity117 -free periods, by means of radioimmunoassay. The nature of the extracted immunoreactivity was characterized by thin-layer chromatography and confirmed by negative ion-chemical ionization gas chromatography/mass spectrometry. @entity117 treatment suppressed urinary @entity57393 excretion by 80%. The fractional elimination of @entity57393 was independent of the rate of @entity3448 infusion and averaged 5.3 +/- 0.8%. Interpolation of metabolite values obtained in @entity117 -free periods onto the linear relationship between the quantities of infused @entity3448 and the amount of metabolite excreted in excess of control values (y = 0.0066x, r = 0.975, P less than 0.001) permitted calculation of the mean rate of entry of endogenous @entity3448 into the circulation as 0.11 ng/kg X min. The rate of disappearance of immunoreactive @entity3448 from the circulation was monoexponential over the first 10 min with an apparent half-life of 7 min. This corresponded to a maximal estimate of the plasma concentration of endogenous @entity3448 of 2.0 pg/ml. These results suggest that ex vivo platelet activation and/or analytical problems confound estimates of endogenous @entity2871 release based on plasma @entity3448 and provide a rationale for seeking longer-lived enzymatic metabolites of @entity3448 in plasma.
