Morphine effects on gentamicin disposition and toxicity in mice

Aryeh Hurwitz, Moshe Garty, Zvi Ben-Zvi

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Morphine has been shown to reduce renal and hepatic clearance of several xenobiotics in rodents. After iv administration of gentamicin, 10 to 30 mg/kg, its plasma levels were elevated in mice given morphine, 20 mg/kg sc. Plasma clearance of gentamicin was nearly halved by morphine, due primarily to lowering of the elimination constant of gentamicin from 0.03 to 0.02 min-1 (p < 0.01). Morphine also significantly reduced urine levels of gentamicin and urine volume. In mice given naloxone, 2 mg/kg sc, morphine did not significantly raise plasma levels of gentamicin nor reduce its elimination into urine. Mice were made tolerant by morphine administration for 9 days at ascending doses to 100 mg/kg twice daily. An acute challenge with morphine, 20 mg/kg, was less effective in raising plasma levels of gentamicin or lowering its urinary elimination in tolerant mice than after chronic saline treatment. Partial tolerance to acutely administered morphine and reversal of morphine effects by naloxone suggest opioid receptor-mediated reduction of glomerular filtration by morphine in mice. Despite marked elevation of plasma gentamicin levels in morphine-treated mice, narcotic administration did not significantly increase the acute toxicity of a single dose of genatamicin. LD50 of acutely administered iv gentamicin was 51.6 mg/kg after saline and 45.3 mg/kg after treatment with morphine, 20 mg/kg sc. However, this dose of morphine enhanced the lethality of intravenously infused gentamicin. Morphine administration significantly reduced the dose of infused gentamicin needed to achieve the critical lethal plasma level.

Original languageEnglish
Pages (from-to)413-420
Number of pages8
JournalToxicology and Applied Pharmacology
Issue number3
StatePublished - 1 Jan 1988
Externally publishedYes

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology


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