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. CONCLUSION: 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.
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. CONCLUSION: 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.
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