Pharmacokinetics of cinnarizine after single and multiple dosing in healthy volunteers

Cinnarizine (CAS 298-57-7) pharmacokinetics were studied after single and repetitive dosing in healthy volunteers. Six young male healthy subjects received a 75 mg tablet and blood samples were drawn for 72 h after medication. Cinnarizine plasma levels were determined by gas chromatography. C(max) was 275 ± 36 ng/ml, t(max) 3.0 ± 0.5 h, AUC extrapolated to infinity 4437 ± 948 ng · h/ml and terminal half-life 23.6 ± 3.2 h. After a 2-week washout period, 5 of these subjects received 75 mg tablets b.i.d. for 15 days. After the administration of doses 1 and 29, blood samples were drawn for 12 h and cinnarizine plasma levels were measured. Cinnarizine accumulated under these conditions. At steady state (dose 29), the observed accumulation factor was 2.79 ± 0.23, being not significantly different from that predicted with the terminal half-life obtained from single dose data, which was 3.37 ± 0.37. AUC_0-12 for dose 29 was 5074 ± 1021 ng · h/ml, being not significantly different from the AUC extrapolated to infinity obtained with the single dose. Results indicate that cinnarizine accumulates with repetitive dosing due to its pharmacokinetic properties.