Aim
Plasma adrenomedullin concentrations are reportedly elevated in patients with renal failure; however, the underlying mechanism is unclear. The aim of this study is therefore to investigate the pharmacokinetic changes of ADM in two renal dysfunction rats.
Methods and results
The pharmacokinetic parameters were calculated from individual plasma ADM concentration vs time curves during and after 1 h intravenous infusion of hADM in rats with acute renal dysfunction by mercury chloride treatment (RD-Ag) and bilateral renal blood flow blockage (RD-BL). At the end of hADM infusion, plasma ADM levels in RD-Ag rats were approximately three times as high as in RD-Bl and normal control rats. We measured a statistically significant positive correlation between ADM C60 and sCr. AUC0–60 during continuous hADM infusion was also significantly increased for RD-Ag than for normal controls. Plasma ADM disappearance after the end of infusion was similar among the three groups. The total systemic clearance of RD-Ag was significantly lower than that of normal rats. Pharmacokinetic analysis revealed that elevated plasma ADM in RD-Ag rats may be caused by a reduced volume of distribution.
Conclusion
These results suggest that decreased plasma ADM clearance in RD-Ag is not due to impaired renal excretion but to a decreased volume of distribution.