FIG 3.

Plasma and tissue pharmacokinetics of DOX in rabbits receiving DOX-supplemented chow. (A) Left panel: DOX concentration-time profile in rabbit plasma following a single DOX dose administered intravenously (i.v.), by oral gavage (p.o.), and subcutaneously (s.c.), as indicated. Right panel: DOX plasma concentrations in rabbits receiving 2,000 ppm DOX in standard chow for 7 days. AM, immediately prior to receiving daily DOX-supplemented feed in the morning; PM, 6 h after receiving DOX feed. (B) Effect of dietary calcium removal on the plasma pharmacokinetics of DOX in rabbits following a single oral dose of 25 mg/kg. (C) Effect of dietary calcium lowering (0.2% total calcium content, or 5-fold lower than in standard chow) on DOX plasma levels in rabbits that received 2,000 ppm DOX in chow for 5 to 7 days. AM and PM time points are as described for right panel A. Data are represented as scatter dot plots of individual animal values and are pooled from two separate experiments with 4 and 6 rabbits, respectively (horizontal bar indicates mean, n = 20 to 34 blood samples from 10 rabbits).