Effects of E. Coli lipopolysaccharide on the pharmacokinetics of ipriflavone and its metabolites, M1 and M5, after intravenous and oral administration of ipriflavone to rats: Decreased metabolism of ipriflavone due to decreased expression of hepatic CYP1A2 and 2C11

Chung, Hanshik; Kang, Hee Eun; Bae, Eun Ju; Lee, Inchul; Kim, Sang G.; Lee, Myung G.

doi:10.1002/jps.21343

Cited by 7 publications

(8 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The results of the in vitro metabolism studies showed the different influences of LPS on hepatic and intestinal drug-metabolizing enzymes. LPS pretreatment was reported to show different influences on the expression of cytochromes P450 in the liver and intestine (Chung et al, 2008), which might be related to the tissuespecific concentrations of the effectors and the severity of pathological changes. The absence of LPS modulation of hepatic metabolism in the current work might have been caused by the different experimental settings, especially the time of initiation of the experiment after LPS administration.…”

Section: Discussionmentioning

confidence: 99%

Increased Systemic Exposure to Rhizoma Coptidis Alkaloids in Lipopolysaccharide-Pretreated Rats Attributable to Enhanced Intestinal Absorption

Ma¹,

Yao²,

Zhong³

et al. 2011

Drug Metab Dispos

View full text Add to dashboard Cite

ABSTRACT:Rhizoma coptidis is a rhizome commonly used in traditional Chinese medicine. After oral administration of rhizoma coptidis extract, the plasma concentrations of its effective alkaloid constituents are so low that their systemic therapeutic actions cannot be explained. This study aimed to investigate the influence of lipopolysaccharide (LPS) on the pharmacokinetics of the rhizoma coptidis alkaloids. Pharmacokinetic experiments were performed with rats; both in vitro absorption and efflux experiments were carried out with everted rat gut sacs, whereas in vitro metabolism experiments were conducted with rat liver microsomes and intestinal S9 fractions. Mucosal changes were evaluated with light microscopy and transmission electron microscopy. The results showed that, in rat plasma, LPS pretreatment increased systemic alkaloid exposure. LPS pretreatment increased the in vitro absorption of the alkaloids and decreased their efflux. The efflux of vinblastine and rhodamine 123, P-glycoprotein substrates, also was decreased. The absorption of fluorescein isothiocyanate-labeled dextran (average molecular mass, 4 kDa), a gut paracellular permeability probe, was not influenced. Obvious damage was observed in the mucosa, but the tight junctions between epithelial cells remained intact. Intestinal, rather than hepatic, alkaloid metabolism was decreased. These findings indicated that LPS pretreatment increased systemic exposure to the alkaloids through enhancement of their absorption, which was related to decreased intestinal efflux and metabolism. The results add to the understanding of why rhizoma coptidis is active despite the low plasma concentrations of the rhizoma coptidis alkaloids measured in normal subjects and experimental animals.

show abstract

Section: Discussionmentioning

confidence: 99%

Increased Systemic Exposure to Rhizoma Coptidis Alkaloids in Lipopolysaccharide-Pretreated Rats Attributable to Enhanced Intestinal Absorption

Ma¹,

Yao²,

Zhong³

et al. 2011

Drug Metab Dispos

View full text Add to dashboard Cite

show abstract

“…The procedures used for the measurement of V max (the maximum velocity) and K m (apparent Michaelis-Menten constant; the concentration at which the rate is one-half of the V max ) for the disappearance of ipriflavone in hepatic microsomes (n 5 6, each) were similar to a reported method [23]. The above microsomes (equivalent to 0.5 mg proteins), 5 ml of methanol containing ipriflavone at final concentrations of 0.5, 1, 2, 5, 10, 20 and 50 mM, and 50 ml of 0.1 M phosphate buffer (pH 7.4) containing 1 mM NADPH were used.…”

Section: Preparation Of Rat Hepatic and Intestinal Microsomesmentioning

confidence: 99%

“…The procedures used for pretreatments of rats including cannulation (early in the morning) of the carotid artery (for blood sampling) and the jugular vein (for drug administration in the intravenous study) were similar to reported methods [2,3,7,20,21,23].…”

Section: Intravenous and Oral Administration Of Ipriflavone To Ratsmentioning

confidence: 99%

“…A blood sample was immediately centrifuged and 50 ml of a plasma sample was stored at À701C (Revco ULT 1490 D-N-S; Western Mednics, Asheville, NC) until used for the HPLC analysis of ipriflavone [25]. The procedures used for the preparation and handling of the 24 h urine sample (Ae 0-24 h ) and gastrointestinal tract (including its contents and feces) sample at 24 h (GI 24 h ) were similar to reported methods [2,3,7,20,21,23].…”

Section: Intravenous and Oral Administration Of Ipriflavone To Ratsmentioning

confidence: 99%

“…The procedures used were similar to a reported method [23]. Liver and intestinal microsomes were resolved by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis on a 7.5% polyacrylamide gel (10 mg protein per lane; n 5 3, each).…”

Section: Preparation Of Rat Hepatic and Intestinal Microsomesmentioning

confidence: 99%

See 2 more Smart Citations

Ipriflavone pharmacokinetics in mutant Nagase analbuminemic rats

Chung

Kang

Yang

et al. 2009

Biopharm & Drug Disp

Self Cite

View full text Add to dashboard Cite

Ipriflavone, a derivative of naturally occurring isoflavones, was primarily metabolized in rats via hepatic CYP1A1/2 and 2C11. Protein and mRNA expression of CYP1A2 in the liver, reported to be increased in mutant Nagase analbuminemic rats (NARs), should influence the pharmacokinetic parameters of ipriflavone. In this study, the contribution of hepatic CYP2C11 and intestinal CYP1A protein to the metabolism and the pharmacokinetic parameters of ipriflavone were examined after intravenous (20 mg/kg) and oral (200 mg/kg) administration to male Sprague-Dawley (control) rats and NARs. There was no change in the protein expression of hepatic CYP2C11. By contrast, CYP1A protein of the intestine increased by almost 100%. After the intravenous administration of ipriflavone to NARs, the Cl(nr) and AUC were unchanged, suggesting that the contribution of the increase in protein expression and mRNA level of hepatic CYP1A2 to hepatic metabolism of the drug in NARs seemed to be almost negligible. However, after the oral administration of ipriflavone to NARs, the AUC was significantly lower than that in the control rats (53.0% decrease), possibly due to the increased intestinal CYP1A that resulted in increased intestinal metabolism and decreased gastrointestinal absorption of ipriflavone in NARs.

show abstract

Determination of ipriflavone in human plasma by LC‐MS and its application in a pharmacokinetic study

Cui

Ding

Leng

et al. 2011

Biomedical Chromatography

View full text Add to dashboard Cite

A sensitive liquid chromatography-mass spectrometric method was developed for the quantification of ipriflavone in human plasma. The method utilized liquid-liquid extraction of plasma with ethyl acetate. A gradient elution was performed on a Hedera ODS-2 column (150×2.1 mm i.d., 5 µm), using a mobile phase consisting of 0.1% formic acid solution and methanol at a flow rate of 0.5 mL/min. The single quadrupole mass spectrometer was operated in selected-ion monitoring mode via positive electrospray ionization interface detecting m/z 239.1 and 285.1 for ipriflavone and diazepam (the internal standard), respectively. To improve the selectivity and sensitivity, the fragment ion m/z 239.1, which was produced by in-source collision-induced dissociation, was chosen as the quantitative ion for ipriflavone. The method was fully validated and applied to a pharmacokinetic study of ipriflavone. After oral administration of a single 200 mg ipriflavone tablet, the C(max,) AUC(0-72 h) , t(1/2) and T(max) were 6.3±6.3 ng/mL, 80.0±69.1 µg h/L, 23.0±8.6 h and 3.4±2.1 h, respectively.

show abstract

Effects of E. Coli lipopolysaccharide on the pharmacokinetics of ipriflavone and its metabolites, M1 and M5, after intravenous and oral administration of ipriflavone to rats: Decreased metabolism of ipriflavone due to decreased expression of hepatic CYP1A2 and 2C11

Cited by 7 publications

References 29 publications

Increased Systemic Exposure to Rhizoma Coptidis Alkaloids in Lipopolysaccharide-Pretreated Rats Attributable to Enhanced Intestinal Absorption

Increased Systemic Exposure to Rhizoma Coptidis Alkaloids in Lipopolysaccharide-Pretreated Rats Attributable to Enhanced Intestinal Absorption

Ipriflavone pharmacokinetics in mutant Nagase analbuminemic rats

Determination of ipriflavone in human plasma by LC‐MS and its application in a pharmacokinetic study

Contact Info

Product

Resources

About