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The diseased lung and drugs
Archives of Toxicology. Supplement. = Archiv Fur Toxikologie. Supplement
|January 1, 1984
Summary
The lung can directly impact drug pharmacokinetics through cellular metabolism and drug uptake. Lung diseases can also indirectly alter drug processing by affecting blood flow to other organs.
Area of Science:
- Pharmacology
- Pulmonary Medicine
- Toxicology
Background:
- The lung's role in drug pharmacokinetics is complex, involving direct metabolic activity and indirect influences from disease states.
- Pulmonary circulation efficiently clears biogenic molecules, suggesting potential for drug modulation.
- Lung cells possess enzymes like mixed function oxidases (MFO) capable of metabolizing xenobiotics.
Purpose of the Study:
- To investigate the lung's direct and indirect effects on drug pharmacokinetics.
- To explore the lung's capacity for drug clearance, metabolism, and potential toxicity.
- To understand how lung diseases influence drug distribution and processing.
Main Methods:
- Review of existing literature on drug-lung interactions.
- Analysis of pulmonary circulation's clearance mechanisms for biogenic molecules.
- Examination of lung cell enzymatic activity (MFO) in xenobiotic metabolism.
Main Results:
- The lung exhibits drug uptake and can metabolize xenobiotics via MFO, though its overall metabolic contribution is likely marginal compared to the liver.
- High MFO content in bronchiolar Clara cells may contribute to lung susceptibility to xenobiotics.
- Respiratory failure can alter blood flow distribution, indirectly affecting drug pharmacokinetics by impacting liver and kidney function.
Conclusions:
- The lung directly influences drug pharmacokinetics through metabolism and uptake, with potential for toxicity from reactive metabolites.
- Lung diseases, particularly those causing respiratory failure, indirectly modulate drug pharmacokinetics by altering systemic blood flow.
- Further research is needed to fully evaluate the significance of pulmonary drug clearance and the lung's susceptibility to xenobiotics.
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