Effects of
renal insufficiency and of aging on the pharmacokinetics of
NS-49, a newly developed
phenethylamine class alpha(1A)-adrenoceptor agonist eliminated mainly by renal excretion, were investigated in rats after a single administration of (14)C-NS-49. The gromerular filtration rate (GFR) in the partially nephrectomized rats was about half that in the
sham-operated rats, and the plasma
creatinine concentration in the former was well above the normal limit. Plasma concentrations of radioactivity after intravenous or
oral administration of (14)C-NS-49 were much higher in the nephrectomized rats than in the intact and
sham-operated rats. As a result, the areas under the plasma concentration-time curve (AUC(0-infinity)) after intravenous and
oral administrations respectively increased 5-fold and 7-fold after partial
nephrectomy. The elimination half-life (t(1/2,beta)) was increased about 2-fold by partial
nephrectomy. The systemic availability for the partially nephrectomized rats remained unchanged, indicative that partial
nephrectomy does not affect the absorption of
NS-49. Plasma concentrations of radioactivity after intravenous or
oral administration of (14)C-NS-49 to 88-week-old rats were higher than in 7-week-old rats, the AUC(0-infinity) value for the aged rats being about two times higher. The aged rats, unlike the nephrectomized rats, showed no marked difference in the t(1/2,beta), value, whereas their V(ss) value was about half that for the young rats. These findings are considered to be caused by physiologic age-related changes; decrease in renal function and loss of body water. Systemic availability in the aged rats did not differ from that in the young, indicative that aging has no effect on the extent of absorption of this
drug.