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Drug induced esophageal lesions studied in vitro
A Ryrfeldt1, K Norbeck, S Reiland
1Department of Toxicology, Karolinska Institutet, Stockholm, Sweden.
Acta Physiologica Scandinavica. Supplementum
|January 1, 1990
Summary
This study introduces an in vitro method to assess drug-induced esophageal irritation using porcine esophagus. Certain oral medications demonstrated potential to cause muscle dysfunction and tissue damage, highlighting the need for careful formulation.
Area of Science:
- Pharmacology
- Gastroenterology
- Toxicology
Background:
- Oral drug formulations can cause esophageal irritation.
- Assessing this potential in vitro is crucial for drug safety.
- Existing methods may not fully capture the complex esophageal response.
Purpose of the Study:
- To develop and validate an in vitro method for evaluating the esophago-irritant potential of oral drug formulations.
- To assess drug effects on esophageal muscle activity, enzyme leakage, and tissue morphology.
- To provide a reliable model for screening drug-induced esophageal injury.
Main Methods:
- Utilized porcine esophageal tissue for in vitro drug exposure.
- Monitored esophageal muscle activity (contraction/relaxation).
- Measured lactate dehydrogenase (LDH) leakage as a marker of cell damage.
- Performed histopathological examination of esophageal mucosa.
Main Results:
- Alprenolol (Aptin) induced marginal esophageal contraction; emepronium bromide (Cetiprin) caused relaxation.
- Increased LDH leakage observed with tested drug formulations compared to controls.
- Histopathology revealed esophageal mucosal softening and necrosis with drugs like doxycycline (Idocyklin) and alprenolol (Aptin).
Conclusions:
- The in vitro method effectively evaluates the esophago-irritant potential of oral drug formulations.
- Specific drugs tested showed varying effects on esophageal muscle and tissue integrity.
- This model aids in understanding and predicting drug-induced esophageal adverse effects.