COMPARATIVE IN VIVO AND IN VITRO EFFECTS OF METHADONE UPON THE Q_O2 OF RAT LIVER, KIDNEY AND JEJUNUM

¹ Division of Pharmacology and Experimental Therapeutics, University of California Medical School, San Francisco, 22

Kidney and liver slices from rats given 10 mgm./kgm. of methadone·HCl subcutaneously and sacrificed 40 minutes later respired at lower rates than similar slices from noninjected animals.

The addition of 0.0005 M methadone·HCl in vitro inhibited the oxygen uptake of kidney and liver slices from noninjected rats and produced additional inhibition of these tissues from injected animals. The effect was most pronounced in the kidney and less so in the liver.

Thus, in moderate quantities methadone·HCl, either given in vivo or added in vitro, significantly reduced the Q_O2 of rat kidney and liver slices as measured by the direct method of Warburg. In contrast, oxygen uptake of jejunum strips was unaffected by methadone·HCl at the concentrations used.

The inhibition of Q_O2 produced by methadone in vitro on kidney and liver slices from noninjected rats at 180 minutes was the same as that produced by methadone in vivo, 40 minutes after injection.