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Effect of dose and dosage interval on the oral bioavailability of docetaxel in combination with a curcumin self-emulsifying drug delivery system (SEDDS)

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Abstract

The present study investigated the effects of a curcumin self-emulsifying drug delivery systems (SEDDS) on the pharmacokinetics of orally administered docetaxel in rats. A single dose of docetaxel was orally administered (30 mg/kg) alone or after oral curcumin SEDDS (25, 50, 100 and 150 mg/kg) administration with time intervals of 0, 15 and 30 min, respectively. After oral administration, the C max and the area under the plasma concentration-time curve (AUC) of docetaxel were significantly increased (0 min, p < 0.05; 15 and 30 min, p < 0.01) by 2.2, 4.7 and 4.6 times and 2.0, 3.8 and 4.1 times compared to that of control group, respectively, after treatment with curcumin SEDDS (100 mg/kg) for each interval. Moreover, The C max of docetaxel was increased by 2.6 and 4.4 times in response to 25 and 50 mg/kg curcumin SEDDS treatment, respectively, the corresponding AUC was increased by about 2.4 and 3.1 times, and consequently the absolute bioavailabilities of docetaxel in these two treatment groups were 7.9 and 10.4%, respectively, which showed a significant increase of about 2.4- and 3.2-fold in comparison to the control value (3.3%). However, no further increase in either AUC or C max values of docetaxel was observed as the curcumin SEDDS dose was increased from 50 to 150 mg/kg. It is worth noting that the presence of curcumin SEDDS did not significantly decrease the systemic clearance, which was shown by the almost unchanged terminal half-life (t 1/2) of docetaxel in all treatment groups. Thus, the enhanced bioavailability of oral docetaxel by curcumin SEDDS seemed to be likely due to an inhibition function of cytochrome P450 (CYP) 3A and P-glycoprotein (Pgp) in the intestines of the rats. However, further in vivo studies are needed to verify these hypotheses.

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Acknowledgments

This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Science and Technology (No. 2010-0024185), and the Mid-career Researcher Program through the NRF grant funded by the MEST (No. 2010-0000363) in South Korea.

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Authors and Affiliations

  1. College of Pharmacy, Yeungnam University, 214-1 Dae-Dong, Gyungsan, Gyungbuk, 712-749, South Korea

    Yi-Dong Yan, Nirmal Marasini, Young Keun Choi, Jong Oh Kim, Chul Soon Yong & Han Gon Choi

  2. Hanmi Research Center, Hanmi Pharm Co., Ltd., Dongtam-myeon, 377-1, Hwaseong, Gyeonggi, 445-913, South Korea

    Jong Soo Woo

  3. College of Pharmacy, Hanyang University, 1271, Sa-3-Dong, Ansan, 426-791, South Korea

    Han Gon Choi

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  1. Yi-Dong Yan
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  2. Nirmal Marasini
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  4. Jong Oh Kim
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Correspondence to Chul Soon Yong or Han Gon Choi.

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Yan, YD., Marasini, N., Choi, Y.K. et al. Effect of dose and dosage interval on the oral bioavailability of docetaxel in combination with a curcumin self-emulsifying drug delivery system (SEDDS). Eur J Drug Metab Pharmacokinet 37, 217–224 (2012). https://doi.org/10.1007/s13318-011-0078-1

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