Renal handling of salicyluric acid in the isolated perfused rat kidney: evidence for accumulation in tubular cells.

The renal handling of salicyluric acid (SU) was studied over a broad concentration range (0-400 micrograms/ml) in the isolated perfused rat kidney (IPK). The accumulation of SU was determined by difference calculations between the SU dose given and the SU amount present in the perfusate and excreted into the urine. SU accumulates highly in the IPK and this accumulation is concentration-dependent. At low perfusate concentrations (5-20 micrograms/ml) there is a sharp increase in the accumulation (100-400 micrograms/g), whereas at higher concentrations (20-100 micrograms/ml) a small increase (400-500 micrograms/g) is seen. The largest part of the accumulation is probably caused by accumulation of SU in the tubular cells. This is a result of the active uptake of SU over the basolateral membrane followed by facilitated diffusion over the brush-border membrane. As a result of the saturation of the active SU uptake, accumulation reaches a maximal value. Excretion of SU in the IPK involves glomerular filtration, active secretion and reabsorption. Reabsorption is probably a passive process, dependent on the urinary flow and pH. The apparent Michaelis-Menten constant of the excretion is 18.7 +/- 1.8 micrograms/ml and the maximum transport capacity is 69.8 +/- 1.4 micrograms/min. The pharmacokinetic parameters of the excretion of SU were in good agreement with previously reported in vivo values.