Pharmacokinetics and system linearity of tea catechins in rat

1. The pharmacokinetics and dose proportionality of three tea catechins wer e 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 uas utilized to describe the bi-exponential disp osition exhibited by the three catechins. 5. Over this dose range, the central distribution volume (V-c) for these ca techins 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 catech ins that mirrored the increases in V-c was observed. 7. The estimates of steady-state volume of distribution (V-ss) were between 0.68 and 2.08 l kg(-1) at the lowest dose, and tended to increase with dos e. 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 acro ss doses were 43, 124, and 222 min respectively, and were invariant with do se. 10. Parallel to V-c, a 2-3-fold dose-dependent increase (p < 0.05) in syste mic 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 <similar to> 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.