Unexpected effect of concomitantly administered curcumin on the pharmacokinetics of talinolol in healthy Chinese volunteers.
OBJECTIVE
To investigate the effect of concomitantly administered curcumin on the pharmacokinetics of the beta1 adrenoceptor blocker talinolol.


METHODS
The study was conducted in a self-controlled, two-period experiment with a randomized, open-labeled design, using 12 healthy volunteers and a wash out period of 1 week between the administration of a single oral dose of 50 mg talinolol and the concomitant administration of curcumin (300 mg day(-1) for 6 days) and a single oral dose of 50 mg talinolol on the seventh day. Concentrations of talinolol were measured in plasma by high-performance liquid chromatography-electrospray ionization mass spectrometry. Non-compartmental analysis was used to characterize talinolol plasma concentration-time profiles, all pharmacokinetic parameters were calculated using DAS: (ver. 2.0) software, and comparisons of mean values were analyzed by the Wilcoxon signed rank test. Differences were considered to be significant at p < 0.05 (two-sided test).


RESULTS
The consumption of curcumin for 6 days reduced the area under the curve (AUC) from predose to infinity (AUC(0-infinity)) of talinolol from 1860.0 +/- 377.9 to 1246.0 +/- 328.2 ng x h mL(-1), the highest observed concentration values (C(max)) were significantly decreased from 147.8 +/- 63.8 to 106.4 +/- 39.9 ng mL(-1), and the CL/F was increased from 27.9 +/- 5.5 to 43.1 +/- 13.4 L x h(-1) (p < 0.05). There was no significant difference in sampling time for C(max) (t(max)) and elimination half-life (t(1/2)) values between the two periods (p > 0.05). The interindividual variability in AUC(0-60) and C(max) of talinolol was comparable in two study periods; the coefficient of variance (CV) of AUC(0-60) and C(max) was 26 and 40% after curcumin versus 21 and 43% after talinolol alone, respectively.


CONCLUSIONS
We suggest that the reduced bioavailability of talinolol is most probably due to the low intraluminal curcumin concentration, or possibly due to the upregulation of further ATP-binding cassette transporters, such as MRP2, in different tissues.
Juan
He
H
Clinical Pharmaceutical Research Institute, Second Xiangya Hospital, Central South University, Changsha 410011, People's Republic of China.
Terhaag
Bernd
B
Cong
Zang
Z
Bi-Kui
Zhang
Z
Rong-Hua
Zhu
Z
Feng
Wang
W
Fen-Li
Su
S
Juan
Song
S
Jing
Tang
T
Wen-Xing
Peng
P
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors; D000319:Adrenergic beta-Antagonists / Q000097:blood / Q000493:pharmacokinetics*; D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D002681:China; D015331:Cohort Studies; D003474:Curcumin / Q000008:administration & dosage* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D004359:Drug Therapy, Combination; D006207:Half-Life; D006801:Humans; D008297:Male; D011412:Propanolamines / Q000097:blood / Q000493:pharmacokinetics*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage* / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011838:Radiation-Sensitizing Agents; C011550:talinolol; D003474:Curcumin