Breast cancer Borstkanker
Conditions
Interventions
1. Co-administration of 600 mg rifampicin during 15 days
2. Dextromethorphan administration (during both clinical periods)
3. Pharmacokinetic sampling.
Sponsors
Erasmus Medical Center - Daniel den Hoed Kliniek, afdeling Interne Oncologie
Eligibility
Inclusion criteria
Inclusion criteria: 1. Histological or cytological confirmed diagnosis of breast cancer, for which treatment with tamoxifen monotherapy is indicated; 2. Use of tamoxifen monotherapy for at least 4 weeks (to guarantee steady-state) and willing to continue the treatment until the end of the study; 3. Age > 18 years; 4. WHO performance < 1; 5. Adequate renal and hepatic functions; 6. Adequate hematological blood counts; 7. Written informed consent; 8. No radiotherapy or chemotherapy within the last 4 weeks before start; 9. No concurrent (over the counter) medication or (herbal) supplements known to induce or inhibit CYP2D6, CYP2C, CYP3A4 and/or P-glycoprotein; 10. No concurrent medication or supplements which can interact with rifampicin; 11. Abstain from grapefruit, grapefruit juice, herbal dietary supplements, and herbal tea during the study.
Exclusion criteria
Exclusion criteria: 1. Pregnant or lactating patients; 2. Impossibility to take oral drugs; 3. Serious illness or medical unstable condition requiring treatment, symptomatic CNS-metastases or history of psychiatric disorder that would prohibit the understanding and giving of informed consent; 4. Contra-indications for rifampicin and/or dextromethorphan use; 5. Use of medications or dietary supplements known to induce or inhibit CYP2D6, CYP2C, CYP3A4 and/or P-glycoprotein; 6. Unwillingness to abstain from grapefruit (juice), (herbal) dietary supplements, herbals, over-the-counter medication (except for low dose of paracetamol and ibuprofen) and other drugs known to seriously interact with CYP3A during the study period; 7. More than one dose of tamoxifen (20 or 40 mg) per day; 8. Non-compliance.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The effects of cytochrome P450 enzyme induction (including CYP3A4, CYP2C and CYP2D6) by rifampicin on the metabolism and plasma pharmacokinetics of tamoxifen and its metabolites. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. The effects of cytochrome P450 enzyme induction on the inter-patient variability in pharmacokinetics of tamoxifen and its metabolites; 2. The influence of genetic polymorphisms in enzymes involved in the metabolism of tamoxifen on the formation of endoxifen, in the presence and absence of rifampicin; 3. Incidence and severity of side effects in the presence and absence of rifampicin; 4. Validation of the previously developed dextromethorphan phenotyping test. | — |
Contacts
Public ContactLisette Binkhorst
Groene Hilledijk 301
Outcome results
None listed