PT  - JOURNAL ARTICLE
AU  - H. M. MEHENDALE
AU  - E. A. EL-BASSIOUNI
TI  - UPTAKE AND DISPOSITION OF ALDRIN AND DIELDRIN BY ISOLATED PERFUSED RABBIT LUNG
DP  - 1975 Nov 01
TA  - Drug Metabolism and Disposition
PG  - 543--556
VI  - 3
IP  - 6
4099  - http://dmd.aspetjournals.org/content/3/6/543.short
4100  - http://dmd.aspetjournals.org/content/3/6/543.full
SO  - Drug Metab Dispos1975 Nov 01; 3
AB  - The uptake, metabolism, and release of aldrin and dieldrin by the lungs were studied by use of isolated perfused rabbit lungs that were artificially ventilated and perfused through the pulmonary artery. Both recirculating and single-pass experiments were conducted using an artificial medium as perfusate. Aldrin accumulated in the lung from the perfusate through two distinct phases of uptake: a rapid phase involving simple diffusion and nonspecific binding and a slower phase representing its metabolic turnover as dieldrin. Dieldrin was not metabolized but accumulated in the lungs by a saturable and a nonsaturable process. Single-pass experiments with aldrin indicated that the initial velocity of uptake could be fitted to one component and a constant representing the rate of metabolism. Uptake of dieldrin was biphasic: one phase independent of the perfusate concentration and the other saturable with respect to the perfusate concentration. By the application of Michaelis-Menten kinetics, the maximum amount of dieldrin accumulation attributable to the saturable component was calculated to be 0.64 µmol/lung. Our results indicate that the accumulation of these chlorinated xenobiotics takes place through the processes of simple diffusion followed by nonspecific tissue binding. There was no evidence for irreversible binding of aldrin or dieldrin, its epoxide, in the lung. While the lung plays a role in metabolizing aldrin to dieldrin followed by a transient storage, neither substrate has the potential for long-term storage in the lung. Copyright © 1975 by The American Society for Pharmacology and Experimental Therapeutics