PT  - JOURNAL ARTICLE
AU  - R J Lutz
AU  - W M Galbraith
AU  - R L Dedrick
AU  - R Shrager
AU  - L B Mellett
TI  - A model for the kinetics of distribution of actinomycin-D in the beagle dog.
DP  - 1977 Mar 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 469--478
VI  - 200
IP  - 3
4099  - http://jpet.aspetjournals.org/content/200/3/469.short
4100  - http://jpet.aspetjournals.org/content/200/3/469.full
SO  - J Pharmacol Exp Ther1977 Mar 01; 200
AB  - A pharmacokinetic model is presented for the distribution of actinomycin-D in the beagle dog. A simple, flow-limited model provides good simulations of the data at doses of 0.6 mg/m2 (0.03 mg/kg) and 2.7 mg/m2 (0.135 mg/kg) for most normal tissues. This implies that uptake of actinomycin-D in vivo is limited by tissue blood flow rate rather than by cell permeability. However, uptake by the testes is restricted by a blood-testis barrier, and a linear membrane-limited model is required to simulate the testis data. Linear binding of actinomycin-D to tissue is suggested by the fact that tissue concentrations are proportional to dose at least up to the lethal dose in dogs. The binding is also rapid and reversible as indicated by the tissue concentration curves which are parallel to the time course of the declining plasma curves.