Evaluating the regulation of transporter proteins and P-glycoprotein in rats with cholestasis and its implication for digoxin clearance

Giroux, Parker; Kyle, Patrick B.; Tan, Chalet; Edwards, Joseph; Nowicki, Michaeł; Liu, Hua

doi:10.4291/wjgp.v13.i3.73

Cited by 2 publications

(2 citation statements)

References 37 publications

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“… 44 Giroux et al. 45 observed a significant increase in MRP1 and OATP4C1 levels in the kidneys of BDL rats, which facilitated the renal tubular excretion of digoxin, while the downregulation of MRP1 and OATP1A4 in the small intestine led to decreased intestinal absorption. Such compensatory extrahepatic transporter adjustments counterbalance the reduced digoxin clearance associated with cholestasis.…”

Section: Cholestasis Affects Pharmacokinetics Parameters By Altering ...mentioning

confidence: 98%

Drug disposition in cholestasis: An important concern

Shang,

Zhang,

Liu

2024

Pharmacology Res & Perspec

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Cholestasis, a chronic liver condition, disrupts bile acid homeostasis and complicates drug disposition, posing significant challenges in medicating cholestatic patients. Drug metabolism enzymes and transporters (DMETs) are pivotal in drug clearance. Research indicates that cholestasis leads to alterations in both hepatic and extrahepatic DMETs, with changes in expression and function documented in rodents and humans. This review synthesizes the modifications in key drug disposition components within cholestasis, focusing on cytochrome P450 (CYP450), drug transporters, and their substrates. Additionally, we briefly discuss certain drugs that have demonstrated efficacy in restoring DMET expression in cholestatic conditions. Ultimately, these insights necessitate a reevaluation of drug selection and dosing guidelines for patients with cholestasis.

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Section: Cholestasis Affects Pharmacokinetics Parameters By Altering ...mentioning

confidence: 98%

Drug disposition in cholestasis: An important concern

Shang,

Zhang,

Liu

2024

Pharmacology Res & Perspec

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“…Uptake of conjugated BA by the liver may be affected by down-regulation of OATP1A1 and up-regulation of OATP1A4 (Slijepcevic et al, 2015). Oatp1a4 is upregulated in the liver and downregulated in the intestine after bile duct ligation (BDL) in rats (Giroux et al, 2022), this seems to indicate that Oatp1a4 is associated with cholestasis. However, in another experiment using 7-day BDL-induced liver dysfunction rats, it was found that the mRNA expression of Oatp1a4 in the liver of BDL rats decreased to 84.8% of that of normal rats (Horiuchi et al, 2009).…”

Section: Oatp1a4 and Cholestasismentioning

confidence: 99%

The role of organic anion transport protein 1a4 in drug delivery and diseases: a review

et al. 2023

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OATP1A4 is an important member of the family of organic anion transporting polypeptides (OATPs), which is generally thought to mediate cellular uptake of endogenous and exogenous substances, such as bile acids, drugs and environmental toxins. Recent studies have found that Oatp1a4 plays an important role in drug passage through the blood-brain barrier and is expected to be an important target for drugs used to treat central diseases. Oatp1a4 has also been associated with various diseases such as cholestasis. differences in Oatp1a4 across age and sex have also become an area of concern for precision drug administration. Therefore, this paper presents a systematic review of Oatp1a4 expression in drug transport and various physiopathological states.

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Evaluating the regulation of transporter proteins and P-glycoprotein in rats with cholestasis and its implication for digoxin clearance

Cited by 2 publications

References 37 publications

Drug disposition in cholestasis: An important concern

Drug disposition in cholestasis: An important concern

The role of organic anion transport protein 1a4 in drug delivery and diseases: a review

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