Phytomedicine. Vol. 7(5). pp. 351·364 C Urban & Fischer Verlag 2000 Pharmacokinetic and oral bioavailability of andrographolide from Andrographis paniculata fixed combination Kan Jang in rats and human A. Panossian ', A. Hovhannisyan ', G. Mamikonyan ', H. Abrahamian", E. Hambardzumyan ', E. Cabrielianl, G. Goukasova", G. Wikman 2 and H. Wagner 3 1Guelbenkian Research & Drug Quality Control Laboratory of ADMTA, Yerevan, Armenia 2Swedish Herbal Institute, Gothenburg, Sweden 3Institute of Pharmaceutical Biology, Ludwig Maximilian University, Munich, Germany "Erebuny Clinic, Yerevan, Armenia Summary Validated analytical methods (HPLC, CE and GC-MS) for determining the amount of andrographolide (AND) in the blood plasma of rats and human volunteers following the oral administration of Andro- graphis paniculata extract (APE) and Andrographis paniculata fixed combination Kan lang tablets were developed and used for the pharmacokinetic study. Andrographolide was quickly and almost com- pletely absorbed into the blood following the oral administration of APE at a dose of 20 mg/kg body wt. in rats. Its bio-availability, however, decreased four-fold when a 10-times-higher dose was used. Since a large part (55 %) of AND is bound to plasma proteins and only a limited amount can enter the cells, the pharmacokinetics of AND are described well by a one-compartment model. Renal excretion is not the main route for eliminating AND. It is most likely intensely and dose dependently metabolized. Follow- ing the oral administration of four Kan lang tablets (a single therapeutic dose, equal to 20 mg of AND) to humans, maximum plasma levels of approximately 393 ng/ml (approx. 1.12 u.M) were reached after 1.5-2 hours, as quantified using a UV diode-array detection method. Half-life and mean residence times were 6.6 and 10.0 hours, respectively. AND pharmacokinetics in humans are explained well by an open two-compartment model. The calculated steady state plasma concentration of AND for multiple doses of Kan lang (after the normal therapeutic dose regimen, 3 x 4 tablets/day, about 1 mg AND/kg body wt.lday) was approximately 660 ng/ml (approx. 1.9 u.M), enough to reveal any anti-PAF effect, partic- ularly after drug uptake when the concentration of AND in blood is about 1342 ng/ml (approx. 3.8 f..lM, while for anti-PAF effect EC so - 5 f..lM). Key words: Andrographis paniculata, andrographolide, pharmacokinetic, capillary electrophoresis, oral bioavailability studies. Introduction Andrographis paniculata Nees is one of the most im- portant medicinal plants, having been used in Chinese and Ayurvedic medicine for gastric disorders, colds, in- fluenza and other infectious diseases [Bensky and Gam- ble, 1993; Cava et al., 1965; D. Chakravati and R. Chakravati, 1952; Chang and But,1987; Dymock et al.,1890; Tang and Eisenbrand 1992; White, 1901]. An extract of A. paniculata, standardized for its content of andrographolide and deoxyandrographolide and called 'Kan lang', has been used extensively in Scandinavia for the last 20 years in treating the common cold. Sev- eral randomized, placebo-controlled, double-blind clinical trials of Kan lang tablets have shown that it has a preventive effect against the common cold. Kan lang 0944-7113/00/07/05-351 $15.00/0