RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Caesalpinia sappan is a medicinal plant native to China popularly used to treat chronic pelvic inflammation, dysmenorrhea and hysteromyoma. Its main bioactive component is brazilin which had presented antibacterial, anti-inflammatory and anti-platelet aggregation activities. To establish a sensitive, selective, reproducible, and accurate high performance liquid chromatographic (HPLC) method for the quantitative determination of brazilin in plasma, and study the pharmacokinetics of brazilin in rats after intravenous administration of brazilin. MATERIALS AND METHODS: Rats received intravenous injection of 25, 50 and 100mg/kg of brazilin. Concentrations of brazilin in plasma were determined by HPLC method at different time points and all pharmacokinetic parameters were estimated by non-compartmental analysis with WinNonLin 6.2 software. RESULTS: After single intravenous doses of 25, 50 and 100mg/kg brazilin in rats, the main PK parameters were as follows: Cmax were 18.1 ± 4.1, 46.7 ± 8.7 and 82.2 ± 9.6 µg/mL; AUC0-24 were 20.4 ± 4.3, 48.7 ± 6.8 and 90.4 ± 10.3 µgh/mL; and t1/2 were 5.4 ± 1.5, 5.8 ± 0.9 and 6.2 ± 1.2h, respectively. CONCLUSION: It showed that the brazilin was eliminated moderately in rat by intravenous injection route with t1/2 of 6h and showed a dose-dependence profile of Cmax and AUC0-24 at the doses of 25~100mg/kg of brazilin for injection in rats.
Assuntos
Benzopiranos/química , Benzopiranos/farmacocinética , Cromatografia Líquida de Alta Pressão/métodos , Animais , Área Sob a Curva , Benzopiranos/sangue , Relação Dose-Resposta a Droga , Meia-Vida , Masculino , Estrutura Molecular , Ratos , Ratos Sprague-Dawley , Sensibilidade e Especificidade , Tinidazol/química , Tinidazol/farmacocinéticaRESUMO
The bioequivalence of two different tablet formulations of tinidazole (CAS 19387-91-8) was determined in healthy volunteers after a single dose in a randomized crossover study, with a 1-week washout period between the doses. Reference and test products were administered to 24 volunteers with 240 mL water after overnight fasting. Plasma concentrations of tinidazole were monitored by a high-performance liquid chromatographic method (HPLC) over a period of 72 h after the administration. The pharmacokinetic parameters AUC(o-t), AUCo-infinity, C(max), T(max), T((1/2)el) and beta were determined from plasma concentration time profile of both formulations and found to be in good agreement with previously reported values. The calculated pharmacokinetic parameters were compared statistically to evaluate bioequivalence between the two brands. The analysis of variance (ANOVA) did not show any significant difference between the two formulations and 90% confidence intervals for the ratio of C(max) (93.9 -102.6%), AUC(o-t) (94.9-101.1%) and AUC(o-infinity) (94.6-100.8%) values for the test and reference products were within the 80-125% interval, satisfying the bioequivalence criteria of the European Committee for Proprietary Medicinal Products and the US Food and Drug Administration Guidelines. These results Indicate that the test and the reference products of tinidazole are bioequivalent and, thus, may be prescribed interchangeably.