title: Lack of effect of mizolastine on the safety and pharmacokinetics of digoxin administered orally in repeated doses to healthy volunteers.
abstract: The effects of mizolatine, a new H1 receptor antagonist, on safety and pharmacokinetics of digoxin were studied in a double-blind placebo-controlled crossover study. After administration of digoxine alone (0.25 mg o.d. for 7 days), 12 healthy young male volunteers (23+/-2 years) received either placebo and digoxin (0.25 mg o.d.) or mizolastine (10 mg o.d.) and digoxin (0.25 mg o.d.) during 7 days. The assessment criteria consisted in hemodynamic and ECG parameters recordings and the pharmacokinetics of digoxin during the last day of coadministration (day 14). No difference between the 2 treatment groups was evidenced on ECG, hemodynamic, and clinical and laboratory safety parameters. No change in AUC and tmax was recorded. No clinically relevant effect of mizolastine on the digoxin pharmacokinetics was found. However, a statistically significant increase in digoxin Cmax (3.03+/-0.18 nmolxl(-1) vs 2.52+/-0.19 nmolxl(-1), p < 0.05) and Cmin (0.99+/-0.08 nmolxl(-1) vs 0.87+/-0.07 nmolxl(-1), p=0.05) occurred after the coadministration vs digoxin alone. It can be concluded that mizolastine and digoxin at therapeutic dosages can be safely coadministered.
authors.affiliation: Synthélabo Recherche, Clinical Pharmacology, Bagneux, France.
authors.forename: S
authors.initials: S
authors.lastname: Chaufour
authors.forename: F
authors.initials: F
authors.lastname: Le Coz
authors.forename: T
authors.initials: T
authors.lastname: Denolle
authors.forename: C
authors.initials: C
authors.lastname: Dubruc
authors.forename: I
authors.initials: I
authors.lastname: Cimarosti
authors.forename: C
authors.initials: C
authors.lastname: Deschamps
authors.forename: N
authors.initials: N
authors.lastname: Ulliac
authors.forename: B
authors.initials: B
authors.lastname: Delhotal-Landes
authors.forename: P
authors.initials: P
authors.lastname: Rosenzweig
mesh_terms: D000328:Adult; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D004077:Digoxin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004311:Double-Blind Method; D004347:Drug Interactions; D004562:Electrocardiography / Q000187:drug effects; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008297:Male
chemical_list: D000889:Anti-Arrhythmia Agents; D001562:Benzimidazoles; D006634:Histamine H1 Antagonists; C076170:mizolastine; D004077:Digoxin