Dose dependency of apparent volumes of distribution for methylene blue in rabbits.

The binding of methylene blue (MB) and chlordiazepoxide (CDP) to rabbit plasma was determined by ultrafiltration. The fractions (f) unbound of these two drugs to the plasma were about 23--29 ad 6--12%, respectively. These fvalues were comparable to binding data of these two drugs to bovine serum albumin. The results supported the previous suggestion stating that protein binding would partly account for relatively high value of apparent volume of distribution (Vd') for MB. Therefore, in order to investigate the distributive profile for MB as compared with that for CDP, pharmacokinetic parameters for MB and CDP were estimated from plasma concentration--time data following simultaneous intravenous administration by a bolus injection and by a contrast rate infusion in rabbits. The Vd' for MB was found to be dependent of dose in contrast with that for CDP by the infusion experiments at three different doses. These evidences assume that MB would be bound to and/or adsorbed on some biological components other than plasma protein.