Inhibitory Potencies of 1,4-dihydropyridine Calcium Antagonists to P-glycoprotein-Mediated Transport: Comparison with the Effects on CYP3A4

  title={Inhibitory Potencies of 1,4-dihydropyridine Calcium Antagonists to P-glycoprotein-Mediated Transport: Comparison with the Effects on CYP3A4},
  author={Miki Katoh and Miki Nakajima and Hiroshi Yamazaki and Tsuyoshi Yokoi},
  journal={Pharmaceutical Research},
AbstractPurpose. Recently, we clarified the inhibitory effects of 13 kinds of 1,4-dihydropyridine calcium antagonists on human cytochrome P450 (CYP) 3A4. It has been reported that the substrates and/or inhibitors are overlapped between CYP3A4 and P-glycoprotein (P-gp). The purpose of this study was to investigate the inhibitory effects of 13 kinds of 1,4-dihydropyridine calcium antagonists on P-gp-mediated transport in order to evaluate the overlapping specificity of the inhibitors between P-gp… 

Species differences of inhibitory effects on P-glycoprotein-mediated drug transport.

The present study revealed that species differences in the inhibitory effects on P-gp-mediated drug transport should not be disregarded among human, monkey, canine, rat, and mouse and will provide useful information for predicting drug interactions mediated by P- gp.

Inhibitory effect of loperamide on cytochrome P450 3A4 in human liver microsomes

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The use of amlodipine, but not of P-glycoprotein inhibiting calcium channel blockers is associated with clopidogrel poor-response.

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Modulation of P-glycoprotein function by amlodipine derivatives in brain microvessel endothelial cells of rats

AbstractAim:To investigate whether the amlodipine derivatives, CJX1 and CJX2, have a modulative effect on P-glycoprotein (P-gp) function in rat brain microvessel endothelial cells

Concentration dependency of modulatory effect of amlodipine on P‐glycoprotein efflux activity of doxorubicin — a comparison with tamoxifen

It was concluded that amlodipine, similar to tamoxifen, modulated the transporter‐dependent transmembrane flux of the P‐gp substrate in a concentration‐dependent manner.

Changes in the Pharmacokinetics of Rosiglitazone, a CYP2C8 Substrate, When Co-Administered with Amlodipine in Rats

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Inhibition of human cytochrome P450 enzymes by 1,4-dihydropyridine calcium antagonists: prediction of in vivo drug–drug interactions

The inhibitory effects of 13 kinds of 1,4-dihydropyridine calcium antagonists clinically used in Japan on human CYP-isoform-dependent reactions were investigated and the possibility of in vivo drug interactions of nicardipine and other drugs which are mainly metabolised by CYP2C9 and/or CYP3A4 was suggested.

P-glycoprotein and cytochrome P-450 3A inhibition: dissociation of inhibitory potencies.

Results demonstrate that, although many P-gp inhibitors are potent inhibitors of CYP3A, a varying degree of selectivity is present and the development and use of P-GP inhibitors with minimal or absent CYP2A inhibitory effects should decrease the impact of drug interactions on the therapeutic use of such compounds.

Interrelationship Between Substrates and Inhibitors of Human CYP3A and P-Glycoprotein

The results indicate that the overlap in substrate specificities of CYP3A and P-gp appears to be fortuitous rather than indicative of a more fundamental relationship.

Effect of Cyclosporin Analogues and FK506 on Transcellular Transport of Daunorubicin and Vinblastine via P-glycoprotein

In the transcellular transport system, lipophilicity may be one of the determinants for the inhibitory effect of various multidrug resistance modulators on the P-glycoprotein-mediated transport.

Overlapping substrate specificities of cytochrome P450 3A and P-glycoprotein for a novel cysteine protease inhibitor.

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Transport of digoxin by human P-glycoprotein expressed in a porcine kidney epithelial cell line (LLC-PK1).

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Restoration of doxorubicin responsiveness in doxorubicin-resistant P388 murine leukaemia cells.

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Effects of Intestinal CYP3A4 and P-Glycoprotein on Oral Drug Absorption—Theoretical Approach

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Role of intestinal P‐glycoprotein (mdr1) in interpatient variation in the oral bioavailability of cyclosporine