Altered drug disposition of the platelet activating factor antagonist apafant in mdr1a knockout mice

European Journal of Pharmaceutical Sciences

Volumn 16, Issue 3, 2002, Pages 119-128

  Leusch, Andreas ^a   Volz, Astrid ^a   Müller, Gabriele ^a   Wagner, Andrea ^a   Sauer, Achim ^a   Greischel, Andreas ^a   Roth, Willy ^a  

^a BOEHRINGER INGELHEIM PHARMA GMBH AND CO KG   (Germany)

Author keywords

Apafant; Digoxin; Disposition; Knock out mice; mdr1a

Indexed keywords

ABC TRANSPORTER; APAFANT; AZEPINE DERIVATIVE; CARBON; GLYCOPROTEIN P; MULTIDRUG RESISTANCE PROTEIN 3; THROMBOCYTE ACTIVATING FACTOR; TRIAZOLE DERIVATIVE; ATENOLOL; CAS 105219565; CYCLOSPORIN A; DIGOXIN; MACROGOL 4000; MANNITOL; PROBENECID; THEOPHYLLINE; THROMBOCYTE ACTIVATING FACTOR ANTAGONIST; TRITIUM; VERAPAMIL;

ANIMAL; AREA UNDER THE CURVE; ARTICLE; BILE DUCT; BLOOD; CELL STRAIN CACO 2; CHEMISTRY; COMPARATIVE STUDY; DRUG ANTAGONISM; GENETICS; HUMAN; INTESTINE MUCOSA; MALE; METABOLISM; MOUSE; MOUSE MUTANT; PHYSIOLOGY; SECRETION; TISSUE DISTRIBUTION; ANIMAL EXPERIMENT; ANIMAL TISSUE; BILIARY EXCRETION; CELL MEMBRANE TRANSPORT; CONCENTRATION RESPONSE; CONTROLLED STUDY; DOSE RESPONSE; DRUG ABSORPTION; DRUG BRAIN LEVEL; DRUG DISPOSITION; DRUG DISTRIBUTION; DRUG EXCRETION; DRUG TRANSPORT; FECES; HUMAN CELL; INTESTINE; ISOTOPE LABELING; KNOCKOUT GENE; KNOCKOUT MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; RADIOACTIVITY; SCINTILLATION; URINARY EXCRETION; WHOLE BODY AUTORADIOGRAPHY;

ANIMALS; AREA UNDER CURVE; ATP-BINDING CASSETTE TRANSPORTERS; AZEPINES; BILE DUCTS; CACO-2 CELLS; CARBON RADIOISOTOPES; HUMANS; INTESTINAL MUCOSA; MALE; MICE; MICE, KNOCKOUT; P-GLYCOPROTEINS; PLATELET ACTIVATING FACTOR; TISSUE DISTRIBUTION; TRIAZOLES; ANIMAL; COMPARATIVE STUDY; HUMAN;

ABSORPTION; BRAIN; RADIOACTIVITY; SCINTILLATION; TISSUE;

DRUG DISPOSITION;

PROTEINS;

EID: 0035996829     PISSN: 09280987     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0928-0987(02)00088-X     Document Type: Article

References (28)

1. Tolerability, safety and efficacy of WEB 2086 in healthy human volunteers
2. Correlation between oral drug absorption in humans and apparent drug permeability coefficients in human intestinal epithelial (Caco-2) cells
3. The influence of donor and reservoir additives on Caco-2 permeability and secretory transport of HIV protease inhibitors and other lipophilic compounds
4. Pharmacodynamics, pharmacokinetics and safety profile of the new platelet-activating factor antagonist apafant in man
5. Expression of the multidrug resistance gene product (P-glycoprotein) in human normal and tumor tissues
6. Inhibition of P-glycoprotein-mediated drug transport: A unifying mechanism to explain the interaction between digoxin and quinidine
7. Probenecid reverses multidrug resistance in multidrug resistance-associated protein-overexpressing HL60/AR and H69/AR cells but not in P-glycoprotein-overexpressing HL60/Tax and P388/ADR cells
8. Biochemistry of multidrug resistance mediated by multidrug transporter
9. Function and expression of multidrug resistance-associated protein family in human colon adenocarcinoma cells (Caco-2)
10. Functional expression of P-glycoprotein in apical membranes of human intestinal Caco-2 cells. Kinetics of vinblastine secretion and interaction with modulators
11. Adult T-cell leukemia cells over-express the multidrug-resistance-protein (MRP) and lung-resistance-protein (LRP) genes
12. Physiologically based pharmacokinetics of digoxin in mdr1a knockout mice
13. Substantial excretion of digoxin via the intestinal mucosa and prevention of long-term digoxin accumulation in the brain by the mdr1a P-glycoprotein
14. Full blockade of intestinal P-glycoprotein and extensive inhibition of blood-brain barrier P-glycoprotein by oral treatment of mice with PSC833
15. Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs
16. The physiological function of drug-transporting P-glycoproteins
17. Normal viability and altered pharmacokinetics in mice lacking mdr1-type (drug-transporting) P-glycoproteins
18. P-Glycoprotein, a gatekeeper in the blood-brain barrier
19. A general pattern for substrate recognition by P-glycoprotein
20. Structure-activity relationship of P-glycoprotein substrates and modifiers
21. Analytical methods validation: Bioavailibility, bioequivalence and pharmacokinetic studies
22. Quantitative distribution studies in animals: Cross-validation of radioluminography versus liquid-scintillation measurement
23. Functional validation of platelet-activating factor receptor sites characterized biochemically by a specific and reproducible [3H]platelet-activating factor binding in human platelets
24. The contribution of P-glycoprotein to pharmacokinetic drug-drug interactions