Pharmacokinetic interaction between ivabradine and carbamazepine in healthy volunteers.
J Clin Pharm Ther
; 36(2): 225-9, 2011 Apr.
Article
in En
| MEDLINE
| ID: mdl-21366652
ABSTRACT
WHAT IS KNOWN AND OBJECTIVE:
Ivabradine is a novel heart rate-lowering agent that selectively and specifically inhibits the depolarizing cardiac pacemaker If current in the sinus node. Our objective was to evaluate a possible pharmacokinetic interaction between ivabradine and carbamazepine in healthy volunteers.METHODS:
The study consisted of two periods Period 1 (Reference), when each volunteer received a single dose of 10 mg ivabradine and Period 2 (Test), when each volunteer received a single dose of 10 mg ivabradine and 400 mg carbamazepine. Between the two periods, the subjects were treated for 15 days with a single daily dose of 400 mg carbamazepine. Plasma concentrations of ivabradine were determined during a 12-h period following drug administration, using a high-throughput liquid chromatography with mass spectrometry analytical method. Pharmacokinetic parameters of ivabradine administered in each treatment period were calculated using non-compartmental and compartmental analysis to determine if there were statistically significant differences. RESULTS ANDDISCUSSION:
In the two periods of treatments, the mean peak plasma concentrations (C(max)) were 16·25 ng/mL (ivabradine alone) and 3·69 ng/mL (ivabradine after pretreatment with carbamazepine). The time taken to reach C(max), t(max), were 0·97 and 1·14 h, respectively, and the total areas under the curve (AUC(0-∞)) were 52·49 and 10·33 ng h/mL, respectively. These differences were statistically significant for C(max) and AUC(0-∞) when ivabradine was administered with carbamazepine, whereas they were not for t(max), half-life and mean residence time. WHAT IS NEW ANDCONCLUSION:
T Carbamazepine interacts with ivabradine in healthy volunteers, and lowers its bioavailability by about 80%. This magnitude of effect is likely to be clinically significant.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Benzazepines
/
Carbamazepine
/
Cardiovascular Agents
/
Heart Rate
/
Anticonvulsants
Type of study:
Prognostic_studies
Limits:
Adult
/
Humans
/
Male
Language:
En
Journal:
J Clin Pharm Ther
Journal subject:
FARMACIA
/
TERAPEUTICA
Year:
2011
Document type:
Article
Affiliation country:
Romania