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Effects of morphine on the disposition of ampicillin in mice
Abstract:
Morphine raised the levels of intravenously administered ampicillin in the plasma of mice. Despite higher ampicillin levels in plasma after administration of morphine, levels of this antibiotic in bile and urine were not elevated. After ligation of the common bile duct, ampicillin levels in plasma were elevated. Morphine caused a further rise in drug levels in plasma of duct-ligated mice. Ampicillin levels in plasma were higher in mice made anephric by prolonged ligation of their external urethras. In such animals, morphine also caused ampicillin levels in plasma to be even higher. These experiments suggest that morphine impairs both renal and hepatobiliary elimination of ampicillin. These effects of morphine were completely reversed by naloxone. In contrast to effects on intravenously administered ampicillin, morphine markedly reduced drug levels in plasma when ampicillin was given by gastric intubation. This resulted from delayed absorption because of retardation of gastric emptying by morphine.
Insights
Morphine increases ampicillin plasma levels by impairing its renal and hepatobiliary elimination in mice. Naloxone reversed these effects, while delayed gastric emptying affected oral ampicillin absorption.
Area of Science:
- Pharmacology
- Drug Interactions
- Toxicology
Background:
- Ampicillin is a widely used antibiotic.
- Morphine is a potent opioid analgesic.
- Understanding drug interactions is crucial for patient safety.
Purpose of the Study:
- To investigate the effect of morphine on ampicillin pharmacokinetics in mice.
- To determine the mechanisms by which morphine alters ampicillin levels.
- To assess the role of renal and hepatobiliary excretion in these interactions.
Main Methods:
- Intravenous and oral administration of ampicillin in mice.
- Surgical manipulation (bile duct ligation, induction of anephria) to assess elimination pathways.
- Measurement of ampicillin concentrations in plasma, bile, and urine.
- Administration of naloxone to evaluate opioid receptor involvement.
Main Results:
- Morphine significantly increased plasma ampicillin levels following intravenous administration.
- Impaired renal and hepatobiliary excretion contributed to elevated ampicillin plasma concentrations.
- Morphine delayed gastric emptying, reducing oral ampicillin absorption.
- Naloxone completely reversed the effects of morphine on ampicillin pharmacokinetics.
Conclusions:
- Morphine impairs both renal and hepatobiliary elimination of intravenously administered ampicillin.
- Morphine's effect on ampicillin pharmacokinetics is mediated through opioid receptors.
- Delayed gastric emptying by morphine significantly impacts oral ampicillin bioavailability.