[Elimination kinetics following repeated administrations of chemotherapeutic agents]

Repeated administrations of the chemotherapeutic agents nalidixic acid, retacillin, oxacillin, ampicillin and gentamicin acts on the transport of organic acids by the kidney. With the exception of nalidixic acid, all the chemotherapeutic agents under study produced a significant dose-dependent increase in the renal clearance of p-aminohippuric acid (PAH) in adult rats aged 55 days. Due to nephrotoxic effects, the renal clearance of PAH is decreased by very high doses of nalidixic acid and gentamicin. In contrast to this, the changes in PAH clearance were less marked in 10-day-old rats in which the ability of the kidney to transport organic acids is low. On repeated administrations of chemotherapeutic agents, one has on principle to consider the production of a diminishing effect due to increased renal clearance.