Emedastine-ketoconazole: pharmacokinetic and pharmacodynamic interactions in healthy volunteers
| Autor: | U Herranz, A Rusca, A Assandri |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Adult
Male Antifungal Agents Adolescent Pharmacology QT interval Emedastine Electrocardiography Pharmacokinetics Cytochrome P-450 Enzyme System Oral administration Anti-Allergic Agents medicine Humans Pharmacology (medical) Drug Interactions Emedastine Difumarate business.industry Drug interaction Middle Aged Ketoconazole Pharmacodynamics Area Under Curve Benzimidazoles business medicine.drug |
| Zdroj: | International journal of clinical pharmacology and therapeutics. 39(3) |
| ISSN: | 0946-1965 |
| Popis: | Objective: To assess the pharmacokinetic and pharmacodynamic interactions of emedastine difumarate, a new antihistamine drug and ketoconazole. Material: Twelve healthy Caucasian volunteers were administered emedastine difumarate 4 mg oral capsules once daily for 10 consecutive days. From day 6 to day 10, ketoconazole 200 mg were co-administered twice daily. Methods: The effects of multiple ketoconazole administration on emedastine kinetics were evaluated by comparing values obtained for pharmacokinetic parameters at steady state, with and without ketoconazole. C ss,max , C ss,min , t max , AUC ss , t 1/2 and Cl ss /F values, obtained after both treatments, were compared. Significant difference was defined as p < 0.05. QTc intervals from ECGs at baseline, after emedastine treatment and after emedastine-ketoconazole co-treatment were statistically compared. Results: Emedastine steady state pharmacokinetics were slightly altered as a result of the ketoconazole co-treatment. AUC ss rose by about 33% (increase ranging from 0.96 to 66.86, p < 0.001) and total clearance decreased by about 30% (ranging from 0.96 to 40.08, p < 0.001) with no change in the half-life. These events did not lead to relevant pharmacodynamic changes, i.e. maximum prolongation of the corrected QT interval (QTc) observed after 5 days co-treatment (day 10) was of about 4%. Rate and severity of anti-H 1 sedation episodes also did not increase on ketoconazole co-treatment. Conclusions: A moderate, but statistically significant interaction between emedastine and ketoconazole was observed. Pharmacodynamic data indicate no increase in the QTc interval during concomitant therapy. This result is consistent with the multiple emedastine metabolic pathways shown in man which supplement the metabolism by different enzymatic isoforms of CYP450. Concomitant treatment with emedastine and ketoconazole in subjects with normal QT intervals can therefore, be undertaken without special precautions. |
| Databáze: | OpenAIRE |
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