Pharmacokinetics and tissue distribution of coptisine in rats after oral administration by liquid chromatography–mass spectrometry

Abstract

Coptisine, one of the main components isolated from Coptidis rhizoma, has been reported to have many beneficial pharmacological effects including anti-inflammatory, anti-hypercholesterolemia, neuroprotective and cardioprotective properties. However, to date the information related to the in vivo pharmacokinetics (PK) of coptisine is very limited. The purposes of our study are to establish a fast and sensitive quantification method of coptisine using liquid chromatography-mass spectrometry (LC-MS) and evaluate the PK profile of coptisine in rats. The calibration curve for coptisine was linear from 0.78 to 50 ng/mL. After single-dose oral administration of coptisine, the mean peak plasma concentration values for groups treated with 30, 75 and 150 mg/kg doses ranged from 44.15 to 66.89 ng/mL, and the mean area under the concentration-time curve values ranged from 63.24 to 87.97 mg/L h. The absolute bioavailability was calculated to range from 1.87 to 0.52%. Coptisine remained in all analyzed samples at low concentrations after oral administration of 30 mg/kg.

Antimalarial activity of traditional Kampo medicine Coptis Rhizome extract and its major active compounds

“…This in vivo assay confirms the potential antimalarial activity of coptisine chloride, one of the major bioactive components of Coptis Rhizome [38]. The oral administration of Coptis Rhizome and Orengedokuto, plasma concentration and tissue distribution of coptisine was detected much lower than the berberine and palmatine suggesting that the poor oral absorption and bioavailability of coptisine and fast elimination rate [55,56].…”

Antimalarial activity of traditional Kampo medicine Coptis Rhizome extract and its major active compounds

“…The content of coptisine is approximately 1/16 of coptisine in Coptis Rhizome [54]. Therefore, our results re ect the contents of these alkaloids in Coptis Rhizome which suggest that the poor oral absorption and bioavailability, and fast elimination rate of coptisine [38,39].…”

Antimalarial activity of traditional Kampo medicine Coptis Rhizome extract and its major active compounds

“…The content of coptisine is approximately 1/16 of coptisine in Coptis Rhizome [54]. Therefore, our results reflect the contents of these alkaloids in Coptis Rhizome which suggest that the poor oral absorption and bioavailability, and fast elimination rate of coptisine [38,39].…”

“…The same dose of injection was performed once a day until day 6. The IP route of administration was used since the previous study revealed that coptisine has low oral bioavailability and poorly absorbed through gastrointestinal tracts [38,39] On day 3 (72 hrs post-infection), the parasitemia level were determined by Giemsa-staining of the tail vein blood smears that was characterized by random counting of the number of parasitized erythrocytes on randomly selected fields of the slide under microscopy of 2,000-4,000 erythrocytes when parasitemia was low (≤10 %) or up to 1000 erythrocytes when parasitemia was higher.…”