Noninvasive estimation of bound and mobile XXXX compounds in the kidney using a radiopharmacokinetic model.

@entity35 @entity900 @entity902
Nephrotoxicity remains a major limitation in the use of @entity900 [ @entity900 ]. Although several strategies are in use to limit this serious side effect, none is fully satisfactory. Classical pharmacokinetic studies of @entity900 have been based on blood and urine samples. As nephrotoxicity plays a significant role in the design of the therapeutic strategy, the kidneys should be considered as a separate state in any model formulated for ultimate control purposes. Previous studies of organ pharmacokinetics have relied on population measurements. The authors have developed an organ compartmental model from individual animal data obtained noninvasively. The eight-compartment model used to represent the distribution of @entity900 considers free and bound @entity902 in plasma, @entity902 in the erythrocytes, mobile and bound @entity902 in the kidneys, mobile and bound @entity902 in the tissues, and @entity902 in the urine. Data were collected from experiments with anesthetized female @entity35 , after intravenous administration of [195mPt] @entity900 . Both arterial and bladder samples, and multiple images obtained with an Anger camera interfaced to a microcomputer were used. The model was estimated from individual data obtained after injection of a bolus of @entity900 (six animals). The model was validated by using it to predict data obtained from forcing the system with a different input function, a 0.5-h intravenous infusion (three animals). The results of this work show that it is possible to noninvasively study drug kinetics in organs that are not readily accessible to direct measurements in an individual, rather than relying on invasive measurements performed on a population.(ABSTRACT TRUNCATED AT 250 WORDS)
