ABSORPTION, DISTRIBUTION AND EXCRETION OF ISONIAZID (NYDRAZID) IN THE DOG

¹ The Squibb Institute for Medical Research, New Brunswick, N. J.

After single or repeated oral doses of isoniazid (Nydrazid) in dogs, it was found that:

1. Peak plasma levels of isoniazid generally occurred within thirty minutes and only occasionally as late as two hours.

2. The average 30-minute plasma concentrations were strictly proportional to and, when expressed as microgm./ml., nearly identical with the oral dose in mgm./kgm. of body weight.

3. The average plasma disappearance rate of isoniazid was 19 per cent per hour.

4. Isoniazid was distributed relatively uniformly in blood plasma, spinal fluid and most tissues sampled.

5. There was no chemically detectable cumulation of the drug in body fluids or tissues with chronic doses tolerated for two to eight months.

6. The urinary excretion of isoniazid as apparently unchanged drug reached its peak within 2 to 4 hours and was practically complete within 24 hours.

7. From 44 to 86 per cent of the administered dose could be accounted for as isonicotinic acid plus apparently unchanged isoniazid in the 24 hour urinary output.

The absorption, distribution, and excretion characteristics of isoniazid in the dog appear to be similar to those reported in man.