Human P-glycoprotein transports cyclosporin A and FK506.

Saeki, Tohru; Ueda, Kazumitsu; Tanigawara, Yusuke; Hori, Ryohei; Komano, Tohru

doi:10.1016/s0021-9258(18)53221-x

Cited by 611 publications

(66 citation statements)

References 20 publications

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“…which is mutated in congenital hyperinsulinism (11,12); the P-glycoproteins MDR1 and MDR3, which transport a series of hydrophobic drugs and phospholipids (13)(14)(15); and the peptide transporter TAP. TAP consists of two subunits, TAP1 and TAP2, and is the only ABC transporter with a unique function in the immune system.…”

Section: Review Articlementioning

confidence: 99%

The Transporter Associated With Antigen Processing (TAP): Structural Integrity, Expression, Function, and Its Clinical Relevance

Ritz

Seliger

2001

Mol Med

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Background:The transporter associated with antigen processing (TAP), a member of the family of ABC transporters, plays a crucial role in the processing and presentation of the major histocompatibility complex (MHC) class I restricted antigens. TAP transports peptides from the cytosol into the endoplasmic reticulum, thereby selecting peptides matching in length and sequence to respective MHC class I molecules. Upon loading on MHC class I molecules, the trimeric MHC class I/␤ 2 -microglobulin/ peptide complex is then transported to the cell surface and presented to CD8 ϩ cytotoxic T cells.

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Section: Review Articlementioning

confidence: 99%

The Transporter Associated With Antigen Processing (TAP): Structural Integrity, Expression, Function, and Its Clinical Relevance

Ritz

Seliger

2001

Mol Med

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“…The quantification of the intestinal P-GP efflux transport kinetics in the current model is based on the efflux transport of cyclosporine at the blood-brain-barrier of rats in vivo (Tanaka et al, 1999) which is attributed to P-GP (Goralski et al, 2006). Using numerical values for the P-GP efflux transport kinetics from in vitro studies (Saeki et al, 1993;Fricker et al, 1996) resulted in a fraction absorbed of ∼0.01, i.e. almost no absorption.…”

Section: Discussionmentioning

confidence: 99%

“…As a cyclic oligopeptide (Rüegger et al, 1976) cyclosporine shows a poor water-solubility but high intestinal permeability (Amidon et al, 1995). It is predominantly a substrate of cytochrome P450 (CYP) 3A4 (Kronbach et al, 1988) and P-glycoprotein (P-GP) (Saeki et al, 1993). Due to a high protein binding predominantly to lipoproteins (Lemaire and Tillement, 1982), the fraction unbound in blood (f U ) is low (1-17%) and depends on measurement methods and examined individuals (Akhlaghi and Trull, 2002).…”

Section: Introductionmentioning

confidence: 99%

Comparing Predictions of a PBPK Model for Cyclosporine With Drug Levels From Therapeutic Drug Monitoring

et al. 2021

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This study compared simulations of a physiologically based pharmacokinetic (PBPK) model implemented for cyclosporine with drug levels from therapeutic drug monitoring to evaluate the predictive performance of a PBPK model in a clinical population. Based on a literature search model parameters were determined. After calibrating the model using the pharmacokinetic profiles of healthy volunteers, 356 cyclosporine trough levels of 32 renal transplant outpatients were predicted based on their biometric parameters. Model performance was assessed by calculating absolute and relative deviations of predicted and observed trough levels. The median absolute deviation was 6 ng/ml (interquartile range: 30 to 31 ng/ml, minimum = −379 ng/ml, maximum = 139 ng/ml). 86% of predicted cyclosporine trough levels deviated less than twofold from observed values. The high intra-individual variability of observed cyclosporine levels was not fully covered by the PBPK model. Perspectively, consideration of clinical and additional patient-related factors may improve the model’s performance. In summary, the current study has shown that PBPK modeling may offer valuable contributions for pharmacokinetic research in clinical drug therapy.

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“…Bei beiden Patienten kam es zu einem Abfall der Ciclosporin-Konzentration im Serum und folglich zur akuten zellulären Abstoβung, die jedoch nach Absetzen des Johanniskrauts voll reversibel war (38). Sowohl Ciclosporin als auch FK-506 (Tacrolimus) sind Substrate von CYP3A4 und MDR1(38,39). Ferner verursacht Johanniskraut eine Abnahme der Bioverfügbarkeit von Indinavir bei HIV-Patienten und von Digoxin(17,35).…”

unclassified

Rolle von nukleären Rezeptoren beim hepatischen und intestinalen Medikamententransport

Kullak‐Ublick

Jung²,

Meier³

2003

Dtsch med Wochenschr

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Human P-glycoprotein transports cyclosporin A and FK506.

Cited by 611 publications

References 20 publications

The Transporter Associated With Antigen Processing (TAP): Structural Integrity, Expression, Function, and Its Clinical Relevance

The Transporter Associated With Antigen Processing (TAP): Structural Integrity, Expression, Function, and Its Clinical Relevance

Comparing Predictions of a PBPK Model for Cyclosporine With Drug Levels From Therapeutic Drug Monitoring

Rolle von nukleären Rezeptoren beim hepatischen und intestinalen Medikamententransport

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