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. Cmax was 275 +/- 36 ng/ml, tmax 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. AUC0-12 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.
Castañeda-Hernández
G
G
Departamento de Farmacología y Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politecnico Nacional, Mexico City.
Vargas-Alvarado
Y
Y
Aguirre
F
F
Flores-Murrieta
F J
FJ
D000328:Adult; D002849:Chromatography, Gas; D002936:Cinnarizine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D008297:Male
D002936:Cinnarizine