Pharmacokinetic and mass balance study of unlabelled and (14)C-labelled emedastine difumarate in healthy volunteers.

摘要

1. In a mass balance study, six healthy male volunteers received a single oral dose of 4 mg (14)C-labelled emedastine difumarate. The pharmacokinetics of the total radioactivity and unchanged drug#10; were assessed over 48 h. Urinary and faecal excretion were measured over 120 h. Additionally, urinary metabolites were investigated. 2. In a single- and multiple-dose pharmacokinetic study, nine male#10; and nine female healthy volunteers received 2 mg oral emedastine difumarate b.i.d. or 4 mg o.d. for 7 consecutive days. The plasma pharmacokinetics were assessed on day 1 and at steady-state. 3. The#10; mass balance study demonstrated almost complete gastrointestinal absorption of the administered dose. A total of 94.2% of the radioactivity was eliminated via the kidneys. Unchanged emedastine in the urine#10; accounted for <5% of dose. 5-Hydroxy, 6-hydroxy and N-oxide metabolites previously identified in the Japanese were present in Caucasian subjects. 4. AUC after single and multiple dosing were#10; dose-proportional. On day 7, no statistical difference in AUC(0-24) could be detected between the two regimens, with AUC = 70.6 +/- 36.1 and 71.7 +/- 52.3 ng h ml(-1), respectively. There were#10; no gender differences in the pharmacokinetics of emedastine. 5. The results corroborate the use of emedastine in a Caucasian population and support the extrapolation of safety and efficacy data from#10; Asians to Caucasians. #10;