THE DISPOSITION OF A HUMAN RELAXIN (HRLX-2) IN PREGNANT AND NONPREGNANT RATS

The pharmacokinetics and tissue distribution of a human relaxin were i nvestigated after intravenous (iv) bolus administration to pregnant or nonpregnant rats. Human gene-2 relaxin (hRlx-2) serum concentrations after iv bolus administration were described as the sum of three expon entials. The pharmacokinetics were comparable in pregnant and nonpregn ant rats. The serum clearance (CL) was 7.4-10.2 ml/min/kg at doses of 46-93-mu-g/kg and was linear in this range. The half-lives were 1.1-2. 0, 15.1-16.4, and 53.7-67.9 min, respectively. The volume of the centr al compartment (V(c)) was 48-79 ml/kg and the volume of distribution a t steady state (V(ss)) was 271-336 ml/kg. Increasing the dose to 463-m u-g/kg increased the dose-corrected area under the serum concentration -time curve and significantly decreased CL and Vss. The distribution o f radioactivity in the tissues of pregnant rats was followed after iv bolus dosing with hRlx-2 internally labeled with S-35-cysteine. Compar ison of the extent of organ uptake of radiolabel after S-35-hRlx-2 or S-35-cysteine administration suggested that the kidneys were the princ ipal site of uptake; the liver was of secondary importance. In perfusi on experiments utilizing livers isolated from pregnant or nonpregnant rats, 36-52% of the dose of hRlx-2 was cleared from the perfusate in 2 hr. These studies showed that the pharmacokinetics of hRlx-2 in rats appeared to be unaffected by pregnancy and suggested that the kidneys and liver both play a role in the elimination of hRlx-2.