curcumin and talinolol

This study was to investigate the effect of concomitantly administered curcumin on the pharmacokinetics of talinolol and association with ABCB1 C3435T genetic polymorphism. A two-phase, randomized, single-blind, crossover study was carried out in 18 healthy male volunteers with different genotypes of ABCB1, including C3435C (CC, n = 6), C3435T (CT, n = 6) and T3435T (TT, n = 6). The pharmacokinetics of talinolol were measured after co-administration of placebo or 1000 mg curcumin capsules once daily for 14 days. The AUC(0-48 h) and AUC(0-∞) of talinolol were increased by 67.0% (95% CI: 1.09~2.25; p = 0.002) and 80.8% (95% CI: 0.92~2.69; p = 0.005) respectively with curcumin co-administration. The C(max) of talinolol was significantly higher after curcumin administration as compared with placebo (p = 0.029).The CL/F of talinolol was decreased by 25.9% (p = 0.005) during the curcumin-treated phase. No significant change in t(max) and t(1/2) of talinolol were observed between the placebo- and curcumin-treated phases. AUC(0-48), AUC(0-∞), C(max) of talinolol were extensively increased and CL(oral)/F decreased in TT subjects. Co-administration of curcumin significantly increased the plasma concentration of talinolol in healthy volunteers. The effect of curcumin on talinolol was associated with ABCB1 genotypes (C3435T).

Topics: Administration, Oral; Adult; ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily B, Member 1; Curcumin; Genotype; Humans; Male; Polymorphism, Single Nucleotide; Propanolamines; Time Factors; Young Adult

To investigate the effect of concomitantly administered curcumin on the pharmacokinetics of the beta1 adrenoceptor blocker talinolol.. 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).. 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.. 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.

Topics: Adrenergic beta-Antagonists; Adult; Area Under Curve; ATP Binding Cassette Transporter, Subfamily B, Member 1; Biological Availability; China; Cohort Studies; Curcumin; Dose-Response Relationship, Drug; Drug Antagonism; Drug Therapy, Combination; Half-Life; Humans; Male; Propanolamines; Radiation-Sensitizing Agents