Pharmacokinetics
Cinnarizine is most commonly taken orally, in pill form, with frequency and amount of dosage varying depending on the reason for taking the medication. Once ingested, the substance is absorbed quite rapidly and reaches a peak plasma concentration in 1–3 hours post-administration. Cmax, the maximum level of the drug in the tested area (typically blood plasma), has been measured to be 275 +/- 36 ng/mL, where tmax, the amount of time that the drug is present at the max amount in the blood, was 3.0 +/-0.5 hours. AUC∞, (the area under the curve extrapolated to infinity) which can be used to estimate bioavailability, was 4437 +/- 948 (ng.h/mL). The half-life elimination varies from 3.4–60 hours, depending on age. However, the mean terminal half-life elimination for young volunteer subjects administered 75 mg cinnarizine, was found to be 23.6 +/- 3.2 hours.
A study that administered 75 mg doses of cinnarizine, twice a day for twelve days, to healthy volunteers, observed that cinnarizine did build up in the body, with a steady-state accumulation factor of 2.79 +/- 0.23. However, the AUCT for this amount of time (T=12 days) was not significantly different from the AUC∞, which was estimated from the single dose administration. As a very weakly basic and also lipophilic compound with low aqueous solubility, cinnarizine is able to cross the blood brain barrier by simple diffusion. It is because of this property that it is able to exert its effects on cerebral blood flow in the brain.
Bioavailability of orally administered cinnarizine is typically low and variable due to high incidence of degradation. However, it has been found than when administered intravenously in lipid emulsion, better pharmacokinetics and tissue distribution were achieved. The lipid emulsion administration had a higher AUC and lower clearance than the solution form, which meant that there was an increased bioavailability of cinnarizine, allowing for an improved therapeutic effect. Plasma pharmacokinetics of cinnarizine administered intravenously follows a three-compartment model first with a fast distribution phase, followed by a slower distribution phase, and ending with a very slow elimination. The Vss (steady state apparent volume of distribution) for lipid emulsion administration was 2x lower (6.871+/- 1.432 L/kg) than that of cinnarizine given in solution (14.018 +/- 5.598 L/kg) and it was found that significantly less cinnarizine was taken up into the lung and brain in the lipid emulsion condition. This is significant because it would reduce the likelihood of toxic side effects in the central nervous system.
Read more about this topic: Sepan