Pharmacokinetics and system linearity of tea catechins in rat.

1. The pharmacokinetics and dose proportionality of three tea catechins were assessed. 2. Male Sprague-Dawley rats (210-230 g) received intravenous (i.v.) doses (50, 100, 200 and 300 mg kg(-1)) of a decaffeinated tea fraction containing (-)-epicatechin (EC: 5%), (-)-epigallocatechin gallate (EGCG: 50%) and (-)-epicatechin gallate (ECG: 13%). 3. Catechins in plasma, urine and faeces were quantitated by HPLC. 4. A two-compartment model was utilized to describe the bi-exponential disposition exhibited by the three catechins. 5. Over this dose range, the central distribution volume (Vc) for these catechins increased significantly (p < 0.05) from 0.17-0.34 to 0.42-0.66 l kg(-1). 6. A concentration-dependent increase in the plasma free fraction of catechins that mirrored the increases in Vc was observed. 7. The estimates of steady-state volume of distribution (Vss) were between 0.68 and 2.08 l kg(-1) at the lowest dose, and tended to increase with dose. 8. Appreciable amount of catechins partitioned into red blood cells (range 9-43%) and was apparently independent of concentration. 9. The mean elimination half-life (t(1/2,beta)) for EC, EGCG and ECG across doses were 43, 124, and 222 min respectively, and were invariant with dose. 10. Parallel to Vc, a 2-3-fold dose-dependent increase (p < 0.05) in systemic clearance (CL) was observed for the three catechins. 11. Urinary recovery was highest (21-31%) for EC, while those for EGCG and ECG was only approximately 3-5%. 12. Faecal recoveries of the catechins were between 0.5 and 5%. 13. In conclusion, the pharmacokinetics of the catechins appeared to be non-linear; dose-dependent changes in xenobiotic distribution might contribute to this observation.