Effects of poloxamer 407-induced hyperlipidemia on the pharmacokinetics of carbamazepine and its 10,11-epoxide metabolite in rats: Impact of decreased expression of both CYP3A1/2 and microsomal epoxide hydrolase

Kim, Young Woo; Kim, Sang Geon; Lee, Inchul; Lee, Myung Gull; Kang, Hee Eun

doi:10.1016/j.euroneuro.2011.10.004

Cited by 33 publications

(43 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Concentrations of total cholesterol (TC), triglyceride (TG) and high density lipoprotein cholesterol (HDL-C) were observed to fall after 12-24 h of dose administration. However, low density lipoprotein cholesterol (LDL-C) was still rising and the other serum lipids were still substantially higher than baseline levels at 48 h from the time of P407 dosing (24). In examining the literature, there is little direct information as to how long the increased lipoprotein levels persist until they return to baseline after each of the two most commonly used single dose levels of P407.…”

Section: Introductionmentioning

confidence: 93%

“…P407 also causes indirect stimulation of 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase which is involved in cholesterol biosynthesis (3,42). _________________________________________ Several groups have used the P407 model of HL for the study of HL on pharmacokinetics and pharmacodynamics of a variety of drugs (4,(7)(8)20,(22)(23)25,33,35). In most of these assessments, the pharmacokinetics of the drugs were studied after dosing at 24 or 36 h from the time of P407 i.p.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The Single Dose Poloxamer 407 Model of Hyperlipidemia; Systemic Effects on Lipids Assessed Using Pharmacokinetic Methods, and its Effects on Adipokines

Chaudhary

Brocks

2013

J Pharm Pharm Sci

View full text Add to dashboard Cite

-Purpose:The induction of hyperlipidemia using poloxamer 407 (P407) is gaining use for studying the effect of the condition on drug pharmacokinetics. Although a single intraperitoneal dose of P407 causes a rapid onset of hyperlipidemia, the initial lipid concentrations are much higher than seen in humans. The hyperlipidemia is also reversible in nature. Here, pharmacokinetic methods were used to assess the P407 dose response on serum lipids, adipokines and cytokines. Methods: Single 0.5 and 1 g/kg doses of P407 were injected into rats followed by blood collection at various times for up to 12 d. Serum was assayed for lipids, selected adipokines and cytokines. Results: As expected, large increases in lipid levels were seen by 36 h after dosing. Using area under the concentration vs. time curve as a measure of systemic lipid exposure, P407 increased serum baseline corrected serum lipids in a nearly dose proportional fashion. The maximum increase in lipids was observed at ~36 h, with most lipids remaining elevated for up to ~180 h, although for the 1 g/kg dose triglyceride concentrations had still not quite returned to baseline by 12 days postdose. In addition to changes in lipids, P407 significantly increased serum leptin and decreased the serum adiponectin concentrations but did not affect cytokine levels. Conclusion: Depending on study aims, for the use of the model it may be beneficial to perform single-dose assessments at time points later than 36 h when the lipoprotein concentrations will be more similar to those seen in patient with hyperlipidemia.

show abstract

Section: Introductionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

The Single Dose Poloxamer 407 Model of Hyperlipidemia; Systemic Effects on Lipids Assessed Using Pharmacokinetic Methods, and its Effects on Adipokines

Chaudhary

Brocks

2013

J Pharm Pharm Sci

View full text Add to dashboard Cite

show abstract

“…Moreover, a decrease in liver metabolic efficiency, including a reduced expression of hepatic CYP3A1/2 (by 51.9% for 3A1 and by 38.4% for 3A2) and 2C11 (by 39.6%), was observed in an HL rat model (Shayeganpour et al 2008). Recently, we found that the PKs of both carbamazepine and its 10,11-epoxide metabolite, substrates of the CYP3A sub-family and microsomal epoxide hydrolase, respectively, were changed in HL rats (Lee et al 2011b). As verapamil is a substrate of the CYP3A sub-family in both humans and rats, alterations in its PKs under conditions of HL are likely.…”

Section: Reasearch Articlementioning

confidence: 98%

“…Male Sprague Dawley (SD) rats (8-10 weeks old, weighing 280-315 g) were purchased from Charles River Company Korea (Seoul, South Korea). The procedures used for housing and handling the rats were similar to previously reported methods (Kang et al 2009;Lee et al 2011b). …”

Section: Animalsmentioning

confidence: 98%

Pharmacokinetics of verapamil and its metabolite norverapamil in rats with hyperlipidaemia induced by poloxamer 407

Yoon

Lee

et al. 2012

Xenobiotica

Self Cite

View full text Add to dashboard Cite

In this study, the pharmacokinetics of verapamil and its active metabolite norverapamil were evaluated following intravenous and oral administration of 10 mg/kg verapamil to rats with hyperlipidaemia (HL) induced by poloxamer 407 (HL rats). The total area under the plasma concentration time curve (AUC) of verapamil in HL rats following intravenous administration was significantly greater (by 11.2%) than in control rats due to their slower (by 11%) non-renal clearance. The oral AUC of verapamil in HL rats was also significantly greater (by 116%) compared with controls, with a larger magnitude than the data observed following intravenous administration. This may have been a result of the decreased intestinal metabolism of verapamil in HL rats. The AUC of norverapamil and AUC(norverapamil)/AUC(verapamil) ratios following intravenous and oral administration of verapamil were unchanged in HL rats. Assuming that the HL rat model qualitatively reflects similar changes in patients with HL, the findings of this study have potential therapeutic implications. Further studies in humans are required to determine whether modification of the oral verapamil dosage regimen in HL states is necessary.

show abstract

“…Hyperlipidemia induced by P407 is also known to cause a downregulation in the expression of several CYP isoforms in liver of male rats, including CYP3A1/2 and CYP2C11, and decrease in mRNA of several proteins involved in drug transport and metabolism Shayeganpour et al 2008). These changes in protein expression may account for alterations in the pharmacokinetics of drugs that D r a f t are intrinsically less highly bound (Lee et al 2012b) or in which the unbound fraction of drug is not affected by the presence of HL (Choi et al 2014;Lee et al 2012c).…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of metformin in the rat: assessment of the effect of hyperlipidemia and evidence for its metabolism to guanylurea

Gabr

El-Sherbeni

Ben‐Eltriki

et al. 2017

Can. J. Physiol. Pharmacol.

View full text Add to dashboard Cite

Metformin pharmacokinetics are highly dependent upon organic cationic transporters. There is evidence of a change in its renal clearance in hyperlipidemic obese patients, and no information on its metabolic fate. To study some of these aspects, the influence of poloxamer 407 (P407)-induced hyperlipidemia on metformin pharmacokinetics was assessed. Control and P407 treated adult male rats were administered 30 mg/kg metformin intravenously (iv). The pharmacokinetic assessments were performed at 2 time points, 36 and 108 h, following the intraperitoneal dose of P407 (1 g/kg). mRNA and protein expressions of cationic drug transporters were also measured.There was no evidence of a change in metformin pharmacokinetics after iv doses as a consequence of short term hyperlipidemia, and a change in transporter mRNA but not protein expression in the 108 h post-P407 treated rats. Urinary recovery of unchanged drug was high (> 90%) but incomplete. Presumed metabolite peaks were detected in chromatograms of hepatocytes and microsomal protein spiked with metformin. Comparative chromatographic elution times and mass spectra suggested that one of the predominant metabolites was guanylurea. Hyperlipidemia by itself did not affect the pharmacokinetics of metformin.Guanylurea is a putative metabolite of metformin in rats.

show abstract

Effects of poloxamer 407-induced hyperlipidemia on the pharmacokinetics of carbamazepine and its 10,11-epoxide metabolite in rats: Impact of decreased expression of both CYP3A1/2 and microsomal epoxide hydrolase

Cited by 33 publications

References 33 publications

The Single Dose Poloxamer 407 Model of Hyperlipidemia; Systemic Effects on Lipids Assessed Using Pharmacokinetic Methods, and its Effects on Adipokines

The Single Dose Poloxamer 407 Model of Hyperlipidemia; Systemic Effects on Lipids Assessed Using Pharmacokinetic Methods, and its Effects on Adipokines

Pharmacokinetics of verapamil and its metabolite norverapamil in rats with hyperlipidaemia induced by poloxamer 407

Pharmacokinetics of metformin in the rat: assessment of the effect of hyperlipidemia and evidence for its metabolism to guanylurea

Contact Info

Product

Resources

About