Pharmacokinetics of chelerythrine and its metabolite after oral and intramuscular administrations in pigs.

The objective of this study was to investigate the single- and multiple-dose pharmacokinetics of chelerythrine (CHE) and its metabolite, dihydrochelerythrine (DHCHE), after oral and IM administrations in pigs.Six crossbreed (Landrace × Large White) female pigs (7-8 weeks old; 24.1 ± 2.6 kg bw) administered oral and IM CHE at a dose of 0.1 mg/kg orally and intramuscularly in a cross-over design. Multiple oral administration was performed at 0.1 mg/kg a time, three times a day at 8-h intervals for three consecutive days. Blood samples were collected from the anterior vena cava and placed into heparinized centrifuge tubes before dosing (time 0 h) and at different times after oral and IM administrations. Pre-treatment plasma was analysed by high-performance liquid chromatography-tandem mass spectrometry.After IM administration, CHE and DHCHE rapidly reached peak concentrations (Cmax, 69.79 ± 15.41 and 3.47 ± 1.23 ng/mL) at 0.42 ± 0.13 and 0.33 ± 0.13 h, respectively. After single oral administration, CHE and DHCHE rapidly increased to reach Cmax of 5.04 ± 1.00 and 1.21 ± 0.35 ng/mL at 1.83 ± 0.26 and 1.67 ± 0.26 h, respectively. The half-life (T1/2) was 2.03 ± 0.26 and 2.56 ± 1.00 h for CHE and DHCHE, respectively. After multiple oral administration, the average steady-state concentrations (Css) of CHE and DHCHE were 2.51 ± 0.40 and 0.6 ± 0.06 ng/mL, respectively.CHE is metabolized rapidly after a single oral administration, multiple daily doses and long-term use of CHE are recommended.

Sanguinarine metabolism and pharmacokinetics study in vitro and in vivo.

Sanguinarine (SA) is a benzo[c] phenanthridine alkaloid which has a variety of pharmacological properties. However, very little was known about the pharmacokinetics of SA and its metabolite dihydrosanguinarine (DHSA) in pigs. The purpose of this work was to study the intestinal metabolism of SA in vitro and in vivo. Reductive metabolite DHSA was detected during incubation of SA with intestinal mucosa microsomes, cytosol, and gut flora. After oral (p.o.) administration of SA, the result showed SA might be reduced to DHSA in pig intestine. After i.m. administration, SA and DHSA rapidly increased to reach their peak concentrations (Cmax , 30.16 ± 5.85, 5.61 ± 0.73 ng/ml, respectively) at 0.25 hr. Both compounds were completely eliminated from the plasma after 24 hr. After single oral administration, SA and DHSA rapidly increased to reach their Cmax (3.41 ± 0.36, 2.41 ± 0.24 ng/ml, respectively) at 2.75 ± 0.27 hr. The half-life (T1/2 ) values were 2.33 ± 0.11 hr and 2.20 ± 0.12 hr for SA and DHSA, respectively. After multiple oral administration, the average steady-state concentrations (Css ) of SA and DHSA were 3.03 ± 0.39 and 1.42 ± 0.20 ng/ml. The accumulation indexes for SA and DHSA were 1.21 and 1.11. The work reported here provides important information on the metabolism sites and pharmacokinetic character of SA. It explains the reasons for low toxicity of SA, which is useful for the evaluation of its performance.