Renal safety pharmacology: value of sensitized experimental models.
The kidneys are an important target for toxic effects of drug candidates. It is mandatory to select accurate, clinically relevant parameters in order to be in a position to detect putative nephrotoxic effects during the safety pharmacology programme. The glomerular filtration rate appears to be of major interest since it is associated with the definition of acute renal failure. Measurement of the renal blood flow, proteinuria, enzymuria, fractional excretion of sodium, etc. are also highly useful to detect any possible renal impact of a new compound. Although the rat is, by far, the most widely used animal species, there are no specific (clinically relevant) reasons to choose it. Various parameters may vary according to the species, sex, strain, age, etc. Since in most cases acute renal failure occurs following administration of drugs in patients with pre-existing risk factors, it is suggested that sensitized animal models be validated and used (salt depletion, dehydration, co-administration of pharmacologic agents, etc.).
Idée
J M
JM
Laboratoires Guerbet, Research Division, Roissy-Charles de Gaulle, France.
D000818:Animals; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced*; D008954:Models, Biological; D010601:Pharmacology, Clinical