Studies on the rate of metabolism of apomorphine in intact mice revealed that the disappearance of injected drug and the appearance of ''bound" apomorphine follow first-order kinetics, with the rate constants 8.15 X lo-' min.rl and 6.07 X min.-*, respectively. Liver perfusion data and experiments on partially hepatectomized rats indicate that this organ is the main site of the metabolism of apomorphine.
REVIOUS PAPERS in this series have described a method for quantitative determination of apomorphine (1) and subsequent application of this method in studying the fate and organ distribution of injected apomorphine (2). In this paper, the kinetics of metabolism and the role of liver in the biotransformation of the drug are described.
EXPERIMENTAL
Kinetics of Metabolism.-The rate of metabolism of apomorphine was studied in intact mice. Apomorphine hydrochloride, 50 mg./Kg., was injected into the tail vein of Albino mice (Webster strain) weighing 20 A 4 Gm. (This dose killed none of five animals in preliminary trials, whereas 60 mg./ Kg. and higher doses killed 4/4 mice.) The drug was given in isotonic saline containing 2 mg./ml. At fixed time intervals, a mouse was homogenized in a Waring Blendor, 1 N hydrochloric acid being used to make 1 : 10 w/v dilution of the mouse. Tenmilliliter and five-milliliter aliquots of the homogenate were assayed for free and total apomorphine, respectively, by the method described previously -Far blank values several untreated mice were carried through the procedure. The blank absorbance values for free and total alkaloid were less than 0.005 and 0.03, respectively. The recoveries of the drug added to mouse homogenates were within the experimental error of *lo%. Table I shows the per cent of the injected dose found as free and "bound" apomorphine a t different time intervals. As is evident in Fig. 1, the disappearance of the injected apomorphine is virtually paralleled by the appearance of "bound" apomorphine.
When the data are plotted on a semilogarithmic scale, a straight line is obtained for at least a ten-(2).