Intestinal secretion of erythromycin base.

Area of Science:

• Pharmacology
• Gastroenterology
• Physiology

Background:

• Erythromycin is a widely used antibiotic.
• Understanding its intestinal transport is crucial for optimizing drug delivery and efficacy.
• Previous studies have not fully elucidated the mechanism of erythromycin's intestinal secretion.

Purpose of the Study:

• To investigate the mechanism and driving forces behind erythromycin secretion into the rabbit jejunum.
• To determine if erythromycin secretion is an active or passive process.
• To identify potential factors influencing erythromycin intestinal transport.

Main Methods:

• In vivo study using anesthetized rabbits with isolated midjejunal segments.
• Infusion of erythromycin into the jugular vein.
• Measurement of erythromycin secretion rates into the jejunal lumen.
• Assessment of protein binding and ultrafiltration of luminal erythromycin.
• Measurement of transmural electrical potential difference across the intestinal mucosa.

Main Results:

• Erythromycin was secreted into the jejunal lumen at a significant rate (0.0136 +/- 0.0023 mg/min).
• Secretion persisted even when luminal concentrations were significantly higher than plasma concentrations, indicating active transport.
• Protein binding did not account for the observed secretion; active erythromycin was present in the lumen.
• A transmural potential difference exceeding 80 mV was required to explain the observed secretion against concentration gradients.

Conclusions:

• Erythromycin undergoes active intestinal secretion into the rabbit jejunum.
• This process is likely driven by the intestinal transmural potential.
• An active transport pathway concentrates erythromycin in the lumen, though the specific endogenous substances using this pathway remain unidentified.