Preclinical factors affecting the pharmacokinetic behaviour of tanshinone IIA, an investigational new drug isolated from<i>Salvia miltiorrhiza</i>for the treatment of ischaemic heart diseases

Bi, Huichang; Zuo, Zhong; Chen, X.; Xu, Chunhai; Wen, Yajie; Sun, Hai Yan; Zhao, Lizi; Pan, Yuexiao; Deng, Ying; Liu, P.-Q.; Gu, Lian‐Quan; Huang, Zhengwei; Zhou, Shu‐Feng; Huang, Min

doi:10.1080/00498250701767675

Cited by 50 publications

(32 citation statements)

References 56 publications

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“…Hepatic tissues were collected from healthy male Sprague-Dawley rats (230-310 g) and stored at 280°C. Liver microsomes were prepared by differential centrifugation as previously described in our report (Bi et al, 2008;Qin et al, 2010b). Human liver microsomes were purchased from BD Biosciences (Franklin Lakes, NJ).…”

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confidence: 99%

“…On the day before the experiment, a light surgery on the right jugular vein of the rats was performed as described in our previously published paper (Bi et al, 2008;Qin et al, 2010b). Afterward, the rats were placed individually in cages to recover and were fasted for 12 hours before the pharmacokinetic study.…”

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confidence: 99%

“…The transport of FK506 across the Caco-2 monolayer was investigated by the methods described in our previous reports Bi et al, 2008;Qin et al, 2010b) with small modifications. Briefly, Caco-2 cells were seeded at 1.0 Â 10 5 cells/cm 2 on polycarbonate membrane Transwell inserts (Corning Inc., Corning, NY) and cultured for 21 days.…”

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confidence: 99%

“…Pharmacokinetic analysis was performed using a noncompartmental analysis by the Pharmacokinetics and Bioavailability Program Package (version 2.1; Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-set University, Guangzhou, China) (Bi et al, 2008;Qin et al, 2010bQin et al, , 2013Jin et al, 2011;Xue et al, 2013). The derived pharmacokinetic parameters of FK506, including the absolute bioavailability of oral doses (F oral ), the hepatic extraction ratio (ER H ), hepatic availability [F H (F H = 1 2 ER H )], gut availability [F G (F G = 1 2 ER G )], and fraction absorbed, were calculated by the methods described previously (Qin et al, 2010b).…”

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confidence: 99%

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In Vivo to In Vitro Effects of Six Bioactive Lignans of Wuzhi Tablet (Schisandra Sphenanthera Extract) on the CYP3A/P-glycoprotein–Mediated Absorption and Metabolism of Tacrolimus

et al. 2013

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We recently reported that Wuzhi tablet (WZ; Schisandra sphenanthera extract) can inhibit P-glycoprotein (P-gp)-mediated efflux and CYP3A-mediated metabolism of tacrolimus (FK506) and thus increase the blood concentrations of FK506. Major active lignans of WZ include schisandrin A, schisandrin B, schisandrin C, schisandrol A, schisandrol B, and schisantherin A. Whether and how these six lignans affect the pharmacokinetics of FK506 remains unclear. Therefore, this study aimed to investigate the effects of these lignans on the first-pass absorption and metabolism of FK506 and the involved mechanisms in vitro and in vivo. The results showed that whole-blood concentrations of FK506 were increased to different degrees following coadministration of the six lignans, respectively. Schisandrol B showed the strongest effect on the increase of the area under the concentration-time curve, the oral bioavailability, the gut processes affecting availability, and the hepatic availability of FK506. The reduction of intestinal first-pass effect contributed most to the increase in oral bioavailability of FK506 when coadministered with schisandrol B. In vitro transport experiment showed that schisandrin A, schisandrin B, and schisandrol B inhibited P-gp-mediated efflux of FK506. In vitro metabolism study showed that the inhibitory effect of these six lignans on FK506 metabolism was dose-dependent. In conclusion, the exposure of FK506 in rats was increased when coadministered with these lignans, and schisandrol B showed the strongest effect. Lignans of WZ inhibited P-gp-mediated efflux and CYP3A-mediated metabolism of FK506, and the reduction of intestinal first-pass affected by the lignans was the major cause of the increased FK506 oral bioavailability.

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confidence: 99%

Section: Downloaded Frommentioning

confidence: 99%

Section: Downloaded Frommentioning

confidence: 99%

Section: Downloaded Frommentioning

confidence: 99%

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In Vivo to In Vitro Effects of Six Bioactive Lignans of Wuzhi Tablet (Schisandra Sphenanthera Extract) on the CYP3A/P-glycoprotein–Mediated Absorption and Metabolism of Tacrolimus

et al. 2013

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“…On the day before the experiment, a light surgery for the rat was performed as described in previously published paper (Bi et al 2008). Briefly, a polyethylene catheter (0.4 mm i.d., 0.8 mm o.d., Portex Ltd, Hythe, UK) was inserted into the right jugular vein under light anesthesia.…”

Section: Pharmacokinetic Studymentioning

confidence: 99%

Comparative pharmacokinetics and bile transformation of R-enantiomer and racemic bambuterol after single-dose intravenous, oral administration in rats and beagle dogs

Guan

et al. 2014

Eur J Drug Metab Pharmacokinet

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This study was to compare pharmacokinetics and bile transformation of R-enantiomer bambuterol with its racemate. Pharmacokinetics of R-enantiomer was investigated after single-dose intravenous and three doses of oral administration to rats and beagle dogs. To compare the pharmacokinetics with racemic bambuterol, the same oral doses of racemic bambuterol were also administrated; the blood and bile samples were collected by cannulation. A validated LC-MS/MS method was used to assess the level of bambuterol in plasma and bile. After single intravenous administration, no significant differences were observed between the two drugs in pharmacokinetic data. After oral dosing of R-bambuterol, the AUCs of R-enantiomer presented linear correlation. After same oral dosing of R-enantiomer and its racemate, all the pharmacokinetic parameters were equivalent. However, the clearance and apparent distribution had different results due to species and administration route difference. The bile transformation of these two compounds was similar and implicated that liver transformation accounted for the major metabolism of them. The bioavailability of R-enantiomer and racemate were comparative and relatively high in beagle dogs. Thus, R-enantiomer had a comparative pharmacokinetic profile and bile transformation with racemic bambuterol in rats and beagle dogs. These findings provided references for further clinical study.

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Microdialysis in the Hepatobiliary System: Monitoring Drug Metabolism, Hepatobiliary Excretion, and Enterohepatic Circulation

Wu¹,

Tsai²

2011

Applications of Microdialysis in Pharmaceutical Science

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Preclinical factors affecting the pharmacokinetic behaviour of tanshinone IIA, an investigational new drug isolated fromSalvia miltiorrhizafor the treatment of ischaemic heart diseases

Cited by 50 publications

References 56 publications

In Vivo to In Vitro Effects of Six Bioactive Lignans of Wuzhi Tablet (Schisandra Sphenanthera Extract) on the CYP3A/P-glycoprotein–Mediated Absorption and Metabolism of Tacrolimus

In Vivo to In Vitro Effects of Six Bioactive Lignans of Wuzhi Tablet (Schisandra Sphenanthera Extract) on the CYP3A/P-glycoprotein–Mediated Absorption and Metabolism of Tacrolimus

Comparative pharmacokinetics and bile transformation of R-enantiomer and racemic bambuterol after single-dose intravenous, oral administration in rats and beagle dogs

Microdialysis in the Hepatobiliary System: Monitoring Drug Metabolism, Hepatobiliary Excretion, and Enterohepatic Circulation

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