A single ascending dose study of epigallocatechin gallate in healthy volunteers.
This randomized, double-blind, placebo-controlled study assessed the safety, tolerability and plasma kinetic behaviour of single oral doses of 94% pure crystalline bulk epigallocatechin gallate (EGCG) under fasting conditions in 60 healthy male volunteers. In each group of 10 subjects, eight received oral EGCG in single doses of 50 mg, 100 mg, 200 mg, 400 mg, 800 mg or 1600 mg, and two received placebo. Blood samples were taken at intervals until 26 h later. The area under the concentration-time curve from 0 h to infinity (AUC(0-infinity)), the maximum plasma concentration (Cmax) of EGCG, the time taken to reach the maximum concentration (Tmax), and the terminal elimination half-life (t1/2z) of EGCG were determined. Safety and tolerability were assessed. In each dosage group, the kinetic profile revealed rapid absorption with a one-peak plasma concentration versus time course, followed by a multiphasic decrease consisting of a distribution phase and an elimination phase. The mean AUC(0-infinity) of total EGCG varied between 442 and 10,368 ng.h/ml. The according mean Cmax values ranged from 130 to 3392 ng/ml and were observed after 1.3-2.2 h. The mean t1/2z values were seen between 1.9 and 4.6 h. Single oral doses of EGCG up to 1600 mg were safe and very well tolerated.
Ullmann
U
U
Roche Vitamins Ltd, Human Nutrition and Health, Research and Development, Basel, Switzerland. uwe.ullmann@roche.com
Haller
J
J
Decourt
J P
JP
Girault
N
N
Girault
J
J
Richard-Caudron
A S
AS
Pineau
B
B
Weber
P
P
D000042:Absorption; D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D002392:Catechin / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006207:Half-Life; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D015990:Placebo Effect; D012016:Reference Values
D002392:Catechin; C045651:epigallocatechin gallate