STUDIES OF CHRONIC MORPHINE POISONING IN DOGS IV. EXCRETION OF MORPHINE IN TOLERANT AND NON-TOLERANT ANIMALS

¹ From the Laboratory of Pharmacology, Stale University of Iowa, Iowa City

1. A method is described for extraction and estimation of morphine in urine and in feces, which gives consistent results in control experiments where small amounts of morphine are added to these excretions.

2. No essential difference in the amount of morphine excreted by tolerant and non-tolerant dogs on the same per kilogram dose could be demonstrated when excretions are studied from day to day.

3. Although the ratio of the excretion in urine and feces varied from day to day, the amount excreted in the urine was always greater than in the feces.

4. The amounts excreted in the urine are roughly proportional to the dose, while the quantities excreted in the feces are more nearly constant and show less variation when different per kilogram doses are compared.

5. While the concentration of morphine in the urine varies considerably from day to day even when fluid intake is kept at a constant level, diuresis is an important factor in urinary excretion of morphine, for when water intake is increased the excretion of the alkaloid in the urine also shows considerable augmentation.

6. The average per cent of the daily dose excreted at all dose levels investigated was approximately 12.5 per cent. The percentage excreted was somewhat greater at the lower dose levels than at the higher levels; but the difference, when only moderate doses are used, is not significant.

7. There is no essential difference in the quantity of morphine excreted by a non-tolerant dog when administration is stopped after the third dose and the quantity excreted by a tolerant dog on withdrawal after prolonged administration. After a single dose, however, the amount excreted is distinctly less than after the third dose. This indicates that part of the dose is retained in the body longer than twenty-four hours as unchanged morphine.