Metabolic clearance and plasma half-disappearance time of D-TRP6 and exogenous luteinizing hormone-releasing hormone.

The MCR and t1/2 of D-Trp6 LRH, a potent analog of LRH, were compared to those of exogenous LRH. Studies were performed on eight normal subjects during and after cessation of a constant infusion of D-Trp6 LRH and LRH. The D-Trp6 LRH and LRH were quantitated individually by sensitive and specific RIAs which did not cross-react with the other peptide infused or fragments of the degraded peptides. High performance liquid chromatography of plasma from a patient infused with D-Trp6 LRH alone yielded one peak, which coeluted with D-Trp6 LRH. The kinetics of peptide clearance were biphasic, with a rapid and a slow component of elimination. The t1/2 of the rapid component of D-Trp6 LRH clearance was 18.7 +/- 1.8 (SEM) min. This was significantly longer (P less than 0.001) than the t1/2 for the LRH of 7.8 +/- 1.1 min. The MCRs for D-Trp6 LRH and LRH were 503.4 +/- 196.4 and 1766.6 +/- 404.3 ml/min, respectively (P less than 0.01). The longer t1/2 of D-Trp6 LRH compared to that of LRH reflects the slower clearance, which is probably due to a decreased rate of degradation. These findings indicated that the enhanced bioactivity of D-Trp6 LRH is in part due to a decreased rate of degradation.