Oral administration of a low dose of midazolam (75�?g) as an in vivo probe for CYP3A activity
| Autor: | Gabriela Bleiber, Amalio Telenti, Thierry Buclin, Gianni Cucchia, Kerry Powell Golay, Daniele Fabio Zullino, Reinhold Kerb, Elisabeth Hustert, Pierre Baumann, Anne-Catherine Aubert, Chin B. Eap |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Adult
Male genetic structures CYP3A medicine.drug_class Midazolam Pharmacology Hypnotic Oral administration In vivo mental disorders medicine Cytochrome P-450 CYP3A Humans heterocyclic compounds Pharmacology (medical) Cross-Over Studies Dose-Response Relationship Drug Chemistry Oxidoreductases N-Demethylating General Medicine Middle Aged Aryl Hydrocarbon Hydroxylases Enzyme Induction Female Ketoconazole surgical procedures operative Anesthesia Sedative psychological phenomena and processes Rifampicin medicine.drug |
| Zdroj: | European journal of clinical pharmacology, vol. 60, no. 4, pp. 237-46 |
| ISSN: | 1432-1041 0031-6970 |
| Popis: | OBJECTIVE: We investigated whether the oral administration of a low dose (75 micro g) of midazolam, a CYP3A probe, can be used to measure the in vivo CYP3A activity. METHODS: Plasma concentrations of midazolam, 1'OH-midazolam and 4'OH-midazolam were measured after the oral administration of 7.5 mg and 75 micro g midazolam in 13 healthy subjects without medication, in four subjects pretreated for 2 days with ketoconazole (200 mg b.i.d.), a CYP3A inhibitor, and in four subjects pretreated for 4 days with rifampicin (450 mg q.d.), a CYP3A inducer. RESULTS: After oral administration of 75 micro g midazolam, the 30-min total (unconjugated + conjugated) 1'OH-midazolam/midazolam ratios measured in the groups without co-medication, with ketoconazole and with rifampicin were (mean+/-SD): 6.23+/-2.61, 0.79+/-0.39 and 56.1+/-12.4, respectively. No side effects were reported by the subjects taking this low dose of midazolam. Good correlations were observed between the 30-min total 1'OH-midazolam/midazolam ratio and midazolam clearance in the group without co-medication (r(2)=0.64, P |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink