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A new principle for estimating hepatic blood flow rates is demonstrated in steady-state experiments in rats in which p-aminohippurate, labeled with either 14C or 3H, was infused into the portal vein, with simultaneous infusion into the tail vein of the same compound labeled with the other isotope. Hepatic blood flow and hepatic extraction ratios were calculated from measurements of urinary and biliary excretion rates and blood concentrations of each isotope. The principle may be used to calculate hepatic blood flow from measurements of urinary excretion and systemic blood concentrations of drug and metabolite after intravenous injections of radiolabeled drug and precursor.

In rats, l-isoproterenol (0.3 mg kg-1 s.c.) reduced the "average total body clearance" (as measured by dose/AUC) and the LD50 of various compounds that are eliminated almost entirely by the kidneys. These effects involve beta-adrenergic receptors since they are blocked by propranolol. Propranolol pretreatment prevented the isoproterenol-induced decreases in renal clearances of methoxy-inulin and tetraethylammonium bromide. Treatment with the alpha-adrenergic-blocking agent, phentolamine, potentiated the decreses in the renal clearances of these substances. The effects of isoproterenol were as marked in hypophysectomized as in intact rats. Peak plasma levels of isoproterenol after subcutaneous administration (0.3 mg kg-1) were about 42 ng ml-1.

In female Sprague-Dawley rats, the renal clearance of cephaloridine decreased as the plasma concentration of the drug declined from above 10 micrograms/ml to below about 3 micrograms/ml, thus suggesting a saturable tubular reabsorption of cephaloridine similar to that shown previously in man. The effects of cephaloridine (250 mg/kg i.v.) were compared with those shown by a group of rats receiving saline and another group of rats receiving probenecid (250 mg/kg i.v.). Probenecid caused a sustained increase in the urate excretion rate. By contrast, cephaloridine produced a relatively small and transient increase in urate excretion, which may have been caused by its diuretic effect. Thus, it is unlikely that the reabsorption mechanism of urate is the principle mechanism by which cephaloridine is reabsorbed.