Effects of diazepam on arterial blood gas concentrations and pH of adult rats acutely and chronically exposed to methadone.

The effects of diazepam alone, and in combination with acute and chronic exposure to methadone, on arterial pH, pCO2 and pO2 in the rat were evaluated. Measurements were made before drug administration and at 15, 30, 60, 120, 180 and 240 min postadministration. Diazepam (20 mg/kg s.c.) did not cause any significant changes in arterial pCO2 or pH. However, it did cause a significant increase in arterial pO2 tension (P less than or equal to .05). The magnitude of this effect was essentially the same after acute and chronic diazepam treatment. The increase in arterial pO2 tension was attributed to a decrease in tissue uptake of oxygen associated with the decrease in body temperature that occurred after diazepam treatment. Acute and, to a far lesser extent, chronic administration of methadone (5 mg/kg/day i.p.) caused significant decreases in arterial pH and pO2 and increases in pCO2 (P less than or equal to .05). When given in combination with methadone, diazepam potentiated markedly the respiratory depressant effects of methadone. The most severe respiratory depression occurred when both drugs were used together acutely. The effects of the acute diazepam-chronic methadone treatment were 100 to 200% greater than those that occurred with the chronic diazepam-chronic methadone treatment, indicating the development of a tolerance to the potentiating ability of diazepam. These results show that there is a real potential for severe respiratory depression when these drugs, methadone and diazepam, are used concurrently, especially for the first time.