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Pharmacokinetic interaction of antimicrobial agents with levomethadon in drug-addicted AIDS patients
N H Brockmeyer1, L Mertins, M Goos
1Universitätshautklinik Essen.
Abstract:
Morphine and its derivatives are metabolized by the liver microsomal enzyme system with a high first-pass effect after oral application. In four of 44 HIV-infected i.v. drug abusers who participated in a levomethadon maintenance program, we observed sustained symptoms of under-dosage and loss of effect of there to fore well-tolerated substitution therapy during rifampin treatment or therapy with zidovudine or fucidic acid. As a pharmacological model substance for cytochrome p 450 enzymes, measurement of antipyrine in serum by high pressure liquid chromatography revealed induction of cytochrome p 450 isoenzymes. The half-life of antipyrine decreased (patient 1 from 11.3 to 8.4 h and patient 2 from 10.7 to 7.6 h after rifampin, patient 3 from 12.2 to 8.6 h after fucidic acid, and patient 4 from 10.6 to 8.6 h after zidovudine). In i.v. drug abusers on levomethadon maintenance programs, adjustment of the levomethadon dosage may be necessary when specific therapy for HIV infection and associated diseases requires the use of drugs known to be potent inducers of the liver microsomal enzyme system.
Insights
HIV patients on methadone maintenance may need dosage adjustments. Certain HIV therapies, like rifampin, can induce liver enzymes, reducing methadone effectiveness and causing under-dosage symptoms.
Area of Science:
- Pharmacology
- Hepatology
- Infectious Diseases
Background:
- Levomethadone maintenance therapy is common for HIV-infected intravenous drug users.
- Morphine derivatives, including methadone, undergo significant liver metabolism with a high first-pass effect.
- Cytochrome P450 enzymes play a crucial role in drug metabolism.
Observation:
- Four out of 44 HIV-infected patients in a levomethadone program experienced under-dosage symptoms.
- These symptoms occurred during treatment with rifampin, zidovudine, or fucidic acid.
- Antipyrine metabolism, a marker for cytochrome P450 activity, was measured.
Findings:
- Rifampin, zidovudine, and fucidic acid induced cytochrome P450 isoenzymes in these patients.
- The half-life of antipyrine significantly decreased, indicating accelerated drug metabolism.
- This enzyme induction likely contributed to the reduced effectiveness of levomethadone therapy.
Implications:
- Levomethadone dosage adjustments may be necessary in HIV patients receiving potent enzyme-inducing drugs.
- Clinicians should monitor for under-dosage symptoms in patients on concurrent therapies.
- Understanding drug-drug interactions is critical for optimizing HIV treatment and substitution therapy.