The Use and Abuse of Toxicokinetics: What Does Actual Data Tell Researchers?

Autor:	Igarashi, Toshiji
Zdroj:	Drug Information Journal; January 1994, Vol. 28 Issue: 1 p285-293, 9p
Abstrakt:	Pharmacokinetic data obtained in 71 toxicity studies on 38 compounds were investigated. Twenty-four studies (33%) were of “I-type” nonlinear kinetics where the plasma concentration did not increase as much as the dose increased, while 14 studies (20%) were of “S-type” nonlinear kinetics where the plasma concentration increased super-proportionally. Some marked increase in plasma concentrations during repeated administration occurred exclusively in “S-type” nonlinear kinetics cases, while decreases were found in some “I-type” kinetics cases. Plasma concentrations at dose levels which produced toxicity were less than the human therapeutic plasma concentrations in 6% of studies and in 18% for those compounds which did not produce toxicity. The intertest compounds difference in items investigated seemed to be much greater than the interstudies (animal species) difference. It should be stressed from these results that the well-designed assessment of systemic exposure in toxicity studies should be requested only in certain representative studies.
Databáze:	Supplemental Index
Externí odkaz:	Zobrazit plný text záznamu