Narcotic effects on phenol red disposition in mice.

Morphine administration reduces phenol red clearance in mice. Increasing subcutaneous morphine doses from 10 to 40 mg/kg caused a progressive increase in plasma phenol red concentrations and reduced dye elimination in urine. Intravenous phenol red given at 50 to 200 mg/kg was cleared from plasma at 24 to 30 microliters/min/kg b. wt. At these dosages of dye plasma clearance of phenol red was reduced at least 33% by morphine pretreatment (20 mg/kg s.c.). Lowered dye clearance by morphine was reflected in smaller apparent volumes of phenol red distribution. The morphine effect on the elimination constant (kel) of phenol red was variable. The narcotic caused a rise in kel at the lowest phenol red dose and lowered this constant at the high phenol red dose. Like morphine, hydromorphone and methadone had an antidiuretic effect in mice and reduced renal elimination of phenol red. Naloxone had no effect on phenol red disposition but reversed completely the effect of morphine. This finding shows that the effect of the narcotic was not due to competition or displacement from transport sites. Morphine did not cause a change in urine pH. Since the urine did not become more acidic after morphine, back diffusion of undissociated due is not likely as the cause of its reduced renal elimination. Reduced renal elimination of phenol red by narcotics is probably due to reduced renal blood flow and glomerular filtration as shown by lowered p-aminohippurate and iothalamate clearance in mice.