Pharmacokinetic interaction studies of tanshinones with tolbutamide, a model CYP2C11 probe substrate, using liver microsomes, primary hepatocytes and in vivo in the rat

Wang, X.; Lee, Wayne; Or, Penelope M.Y.; Yeung, John H.K.

doi:10.1016/j.phymed.2009.07.013

Cited by 42 publications

(34 citation statements)

References 26 publications

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“…TOL hydroxylase activity was assessed as a marker activity for rat CYP2C11 (Wang et al, 2010). The activity was determined as follows: A typical incubation mixture (final volume of 0.2 ml) contained 100 mM potassium phosphate buffer (pH 7.4), RLM (0.2 mg/ml), and TOL (500 mM) dissolved in methanol (#1% v/v final concentration).…”

Section: Methodsmentioning

confidence: 99%

Carbamazepine-Induced Liver Injury Requires CYP3A-Mediated Metabolism and Glutathione Depletion in Rats

et al. 2015

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Carbamazepine (CBZ) is widely used as an antiepileptic agent and causes rare but severe liver injury in humans. It has been generally recognized that reactive metabolites formed via the metabolic activation reaction contribute to the onset of liver injuries by several drugs. However, the role of CBZ metabolism in the development of liver injury is not fully understood. In this study, we developed a novel rat model of CBZ-induced liver injury and attempted to elucidate the associated mechanisms by focusing on the metabolism of CBZ. The repeated administration of CBZ for 5 days in combination with L-buthionine sulfoximine (BSO), a glutathione (GSH) synthesis inhibitor, resulted in increases in the plasma alanine aminotransferase (ALT) levels and centrilobular necrosis in the liver that were observed in various degrees. The CBZ and 2-hydroxy-CBZ concentrations in the plasma after the last CBZ administration were lower in the rats with high plasma ALT levels compared with those with normal plasma ALT levels, showing the possibility that the further metabolism of CBZ and/ or 2-hydroxy-CBZ is associated with the liver injury. Although a single administration of CBZ did not affect the plasma ALT levels, even when cotreated with BSO, pretreatment with dexamethasone, a CYP3A inducer, increased the plasma ALT levels. In addition, the rats cotreated with troleandomycin or ketoconazole, CYP3A inhibitors, suppressed the increased plasma ALT levels. In conclusion, reactive metabolite(s) of CBZ produced by CYP3A under the GSH-depleted condition might be involved in the development of liver injury in rats.

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Section: Methodsmentioning

confidence: 99%

Carbamazepine-Induced Liver Injury Requires CYP3A-Mediated Metabolism and Glutathione Depletion in Rats

et al. 2015

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“…Tolbutamide is metabolized by CYP2C9 in humans and by CYP2C11 in rats 17) , but the activity of both enzymes can be evaluated as (S)-warfarin hydroxylase activity 18) . In the present study in rats, we observed an interaction of CFE with tolbutamide in vivo, in terms of hypoglycemia and induction of hepatic CYP2C.…”

Section: Discussionmentioning

confidence: 99%

<i>Coleus forskohlii</i> Extract Attenuates the Hypoglycemic Effect of Tolbutamide <i>in vivo via</i> a Hepatic Cytochrome P450-Mediated Mechanism

Yokotani

Chiba

Sato

et al. 2014

Journal of the Food Hygienics Society of Japan

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This in vivo study in rats evaluated whether Coleus forskohlii extract (CFE) taken orally interacted with tolbutamide, a hypoglycemic drug metabolized by CYP2C enzymes. Rats were fed 0 , 0.3 , 1 (w/w) CFE diet for 2 weeks, followed by 0 CFE diet for 1 day. They were then given 40 mg/kg tolbutamide by intragastric gavage. Blood glucose level was determined up to 6 h after tolbutamide administration. CFE treatment increased total CYP content and various CYP subtypes in the liver. In particular, increases in activity and protein expression were noted for the CYP2B, CY-P2C, and CYP3A subtypes. CFE treatment dose-dependently attenuated both the hypoglycemic action of tolbutamide at 6 h and the plasma concentration of tolbutamide. The activity of (S)-warfarin 7-hydroxylase, a CYP2C enzyme was negatively correlated with plasma tolbutamide level, which also showed a negative correlation with the reduction of blood glucose level. These results indicate that CFE induced hepatic CYPs in rats and attenuated the hypoglycemic action of tolbutamide via a hepatic CYP2C-mediated mechanism.

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“…Cytochrome P450 content of the rat liver microsomes was quantified as previously described [20]. The HPLC analysis of 4-hydroxytolbutamide was as previ-ously described [21]. The inhibitory effect of CuE on CYP2C11 was evaluated by the percentage of the formation of 4-hydroxytolbutamide compared with the control.…”

Section: 1mentioning

confidence: 99%

“…Sulfaphenazole (5-50 µmol L 1 ), a selective rat CYP2C11 inhibitor, was used as a positive control [21,22]. The mode of inhibition was evaluated by visual inspection of Lineweaver-Burk plots, which were obtained from Michaelis-Menten non-linear regression equation.…”

Section: Analysis Of Inhibition Kineticsmentioning

confidence: 99%

“…A single dose of tolbutamide (10 mg kg 1 ) was given via caudal vein 60 min after the treatment with CuE. The dosage of tolbutamide used was based on similar herb-drug interaction study carried out previously [21]. Serial blood samples (approximately 0.5 mL) were collected via the orbital venous plexus at 10, 20, 30, 60, 90, 120, 240 and 360 min after tolbutamide administration.…”

Section: Effects Of Cue Treatments On the Pharmacokinetics Of Tolbutamentioning

confidence: 99%

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In vitro and in vivo evaluation of cucurbitacin E on rat hepatic CYP2C11 expression and activity using LC-MS/MS

Ding

Qin

et al. 2015

Sci. China Life Sci.

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This study explored the effects of cucurbitacin E (CuE), a bioactive compound from Cucurbitaceae, on the metabolism/ pharmacokinetic of tolbutamide, a model CYP2C9/11 probe substrate, and hepatic CYP2C11 expression in rats. Liquid chromatography-(tandem) mass spectrometry (LC-MS/MS) assay was used to detect tolbutamide as well as 4-hydroxytolbutamide, and then successfully applied to the pharmacokinetic study of tolbutamide in rats. , i.p.) for 3 d did not affect CYP2C11 expression. These findings demonstrated that CuE competitively inhibited the metabolism of CYP2C11 substrates but had no effect on rat CYP2C11 expression. This study may provide a useful reference for the reasonable and safe use of herbal or natural products containing CuE to avoid unnecessary drug-drug interactions. cucurbitacin E, CYP2C11, LC-MS/MS, pharmacokinetic, tolbutamide Citation:Lu J, Ding TG, Qin X, Liu MY, Wang X. In vitro and in vivo evaluation of cucurbitacin E on rat hepatic CYP2C11 expression and activity using LC-MS/MS. Sci China Life Sci, 2017, 60: 215-224,

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Pharmacokinetic interaction studies of tanshinones with tolbutamide, a model CYP2C11 probe substrate, using liver microsomes, primary hepatocytes and in vivo in the rat

Cited by 42 publications

References 26 publications

Carbamazepine-Induced Liver Injury Requires CYP3A-Mediated Metabolism and Glutathione Depletion in Rats

Carbamazepine-Induced Liver Injury Requires CYP3A-Mediated Metabolism and Glutathione Depletion in Rats

<i>Coleus forskohlii</i> Extract Attenuates the Hypoglycemic Effect of Tolbutamide <i>in vivo via</i> a Hepatic Cytochrome P450-Mediated Mechanism

In vitro and in vivo evaluation of cucurbitacin E on rat hepatic CYP2C11 expression and activity using LC-MS/MS

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