Pharmacokinetic Study of Andrographis paniculata Tablets in Healthy Thai Male Volunteers

Pharmacokinetics of andrographolide, main active compound contained in Andrographis paniculata product, was investigated in healthy Thai male volunteers. The bio-analytical method using HPLC for the determination of andrographolide in plasma was developed and validated following US FDA and Thailand guidelines for the bioavailability and bioequivalence studies. Six healthy Thai male volunteers were enrolled in the study. Each was administered with 3 doses (3, 6 and 9 tablets) of A. paniculata tablet which is equivalent to 29.55, 59.10 and 88.65 mg of andrographolide, respectively. Blood samples were pretreated by using C-18 solid phase cartridges before injecting into the HPLC. The result of this study demonstrated the individual variation of bioavailability among subjects. The concentration-time profile of andrographolide in plasma was obtained from a volunteer taking the highest dose. The peak concentration (Cmax) was 335.85 ng/mL and reached the peak time (Tmax) at 1 hour. Andrographolide was neither detected in plasma samples from the lower doses nor detected from other volunteers. However, an individual peak was detected in all plasma samples obtained from the volunteers taking A. paniculata products. A characteristic profile demonstrated the possibility of this peak being a metabolite of andrographolide. The chromatography assumed to be that of a compound polar than andrographolide. Tmax of this compound was also longer than that of andrographolide. The peak in the chromatogram did not appear in the blank plasma or in the extract of A. paniculata. Moreover, the peak response-time profiles of this compound were correspondent to the pattern of the concentration-time profile in pharmacokinetic study. Thus it can be concluded that the saturated metabolism process of andrographolide possibly occurred at high dose.