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[Enzymatic induction during isoniazid therapy (author's transl)].
Pathologie-Biologie
|October 1, 1979
Summary
Isoniazid increases urinary D-glucaric acid, indicating enzyme induction, with higher levels in slow acetylators. Co-administration with phenobarbital further stimulates this induction.
Area of Science:
- Pharmacology
- Biochemistry
- Toxicology
Context:
- Isoniazid is a primary drug for tuberculosis treatment.
- Individual variations in drug metabolism, particularly acetylation, affect isoniazid efficacy and toxicity.
- Enzyme induction by drugs can alter their own metabolism and that of other substances.
Purpose:
- To investigate enzyme induction by isoniazid using urinary D-glucaric acid levels.
- To compare the induction response in slow and fast isoniazid acetylators.
- To assess the effect of co-administering phenobarbital, a known enzyme inducer, with isoniazid.
Summary:
- Isoniazid administration significantly increased urinary D-glucaric acid excretion in both slow and fast acetylators, signifying enzyme induction.
- Fast acetylators showed a 1.8-fold increase in D-glucaric acid over 30 days, while slow acetylators exhibited a more pronounced 3-fold increase after a delayed rise.
- Co-administration of phenobarbital with isoniazid potentiated enzyme induction in both patient groups. Plasmatic free isoniazid levels suggested that phenobarbital increased isoniazid acetylation rate in slow acetylators.
Impact:
- This study highlights differential enzyme induction responses to isoniazid based on acetylation status.
- Findings suggest potential interactions between isoniazid and other drugs affecting hepatic enzyme activity.
- The results raise important considerations regarding isoniazid's hepatic toxicity, particularly in slow acetylators receiving enzyme-inducing co-medications.