or route of administration. Others (4) report that urinary excretion is 20 percent with a 
daily dose of 75 mg., but that this declines to 5 percent when tte dosage level reaches 
more than 400 mg. daily. Total excretion, however, remains at 25 mg. per 24 hour period 
within a dosage range of 200 to 400 mg. daily. The percentage level of urinary excretion 
of levomepromazine is around 12 percent with daily doses of 17, 100, and 125 mg. 
It has recently been reported (5) that in cattle, approximately 12 percent of intra- 
venously injected doses of 0.19, 0.25, and 0.4 mg. of chlorpromazine hydrochloride per 
pound of bodyweight was excreted in the urine during the 24-hour period following 
injection. 
It has been reported (6) that chlorpromazine can be found in the urine of humans for 
4 to 12 days following withdrawal and this variation does not depend upon dosage level 
alone. It has been demonstrated (7) that following doses as massive as 1,000 mg. per 
day, the blood of humans does not contain more than 0.4 mg. per 100 cc., while not even 
a trace is present in the cerebrospinal fluid. Only 2 to 4 percent appears in the urine in 
unchanged form whether the material is injected or given by mouth. 
Accumulation in Tissues 
Concentration levels of chlorpromazine in the tissues following treatment vary 
widely. Kok (8) reports that following a subcutaneous injection of 150 MM’ per kg. into 
rabbits, tissue concentrations in MM per liter of blood or per kg. of tissue were as 
follows: Blood, 3.6; liver, 30; lung, 470; skeletal muscle, 11; brain, 51; and heart, 45, 
In a recent investigation (9) chlorpromazine concentration was found to be 520 mg. per 
kg. of liver and 90 mg. per kg. of brain following intramuscular injection into rats of 
25 mg. of drug per 100 gm. of bodyweight. In another investigation (10) it was found that 
chlorpromazine accumulates in unequal concentrations in the various parts of the brain. 
In cattle slaughtered 8 hours after injection of 0.4 mg. chlorpromazine per lb. body- 
weight, small residues were found inthe fat, brain, heart, lung, and kidney of the animals, 
In cattle slaughtered 72 hours after intravenous injection, no chlorpromazine could be 
detected. No chlorpromazine was found in the muscle of treated animals (5). 
Metabolism 
Only about 1 percent of a 20 mg.per kg. bodyweight intravenous dose of chlorproma- 
zine injected into dogs appears unchanged in the urine according to Salzman et al. (11), 
while 12 percent appears as the sulphoxide. When this metabolite is injected, only 20 
percent appears unchanged in the urine. They also report (12) that two metabolites other 
than the sulphoxide are present as is shown by chromatography. The drug disappears 
relatively slowly from the tissues, the amount remaining 7 hours after injection being 
of the same order as that remaining after 1 hour. However, the small amount of the drug 
found in the plasma at 1 and 3 hours disappeared by the seventh hour. 
An important means of chlorpromazine metabolism detoxification in man is hydroxy - 
lation followed by conjugation with glucuronic acid according to Lin, e al. (13). Young, 
et al. (14) reported the recovery of 40 percent of the radioisotope of C!4 chlorpromazine 
added to rabbit and rat liver homogenates as cl4o, demonstrating that the liver is at 
least able to lower the pharmacological activity of the drug. The appearance of cl4o, in 
air expired by rats given labeled chlorpromazine has been demonstrated by Ross (15), 
This is evidence that the side chain is metabolized, From one group of rats given 15 mg. 
of the drug per kg. bodyweight by mouth, 17 percent of the isotope was recovered from 
expired air during the first 6 hours following administration. A second group of rats 
pretreated with daily doses equal to the labeled dose of the drug for 10 days prior to the 
oral administration of 15 mg. of radioactive chlorpromazine released 12 percent of the 
administered isotope in 6 hours. Rats given 2 mg. of the drug per kg. bodyweight intra- 
venously also released 12 percent of the radioactive material in 6 hours. 
2uM is equivalent to micronole, or 1 millionth of the molecular weight of a given compound, 
220 
