Pharmacokinetics of cyproheptadine hydrochloride in mice and beagle dogs, tissue distribution, and excretion properties of cyproheptadine hydrochloride in mice

Cyproheptadine hydrochloride (CYP) is a typical antihistamine with antiserotonergic, blocking H1 receptor, anticholine, anti‐inflammatory and anti‐allergic effects. To investigate the pharmacokinetics, biodistribution, and excretion, the liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) method was established and validated the CYP concentrations in the plasma of beagle dogs and the biological matrix of mice. CYP was quickly absorbed into the bloodstream and widely distributed to various tissues. The area under the curve (AUC)0–t and peak concentration of CYP were increased with the dose after administration. At the equal dose, the bioavailability of intramuscular injection in mice and beagle dogs was 81.1% and 79.1%. The tissue distribution experiments suggested that CYP would not accumulate for a long time in vivo. CYP levels in tissues peaked after 15 min of injection, and the drug concentrations in the kidney and lung were higher than those in other tissues. For excretion, the cumulative urinary excretion of CYP within 156 h after intramuscular injection in mice accounted for (1.2 ± 0.1)% of the total administration dose. The feces excretion of the drug prototype was below the lower limit of quantitation. High sensitivity and strong specificity are observed based on the established method of LC‐MS/MS, which was successfully applied to the pharmacokinetics, tissue distribution, and excretion studies of CYP.