The DOI matches its Crossref record.
Absence of the mdr1a P-Glycoprotein in mice affects tissue distribution and pharmacokinetics of dexamethasone, digoxin, and cyclosporin A.
Open accessAbstract
We have previously shown that absence of the mouse mdr1a (also called mdr3) P-glycoprotein in mdr1a (-/-) "knockout" mice has a profound effect on the tissue distribution and elimination of vinblastine and ivermectin, and hence on the toxicity of these compounds. We show here that the mouse mdr1a and the human MDR1 P-glycoprotein actively transport ivermectin, dexamethasone, digoxin, and cyclosporin A and, to a lesser extent, morphine across a polarized kidney epithelial cell layer in vitro. Injection of these radio-labeled drugs in mdr1a (-/-) and wild-type mice resulted in markedly (20- to 50-fold) higher levels of radioactivity in mdr1a (-/-) brain for digoxin and cyclosporin A, with more moderate effects for dexamethasone (2- to 3-fold) and morphine (1.7-fold). Digoxin and cyclosporin A were also more slowly eliminated from mdr1a (-/-) mice. Our findings show that P-glycoprotein can be a major determinant for the pharmacology of several medically important drugs other than anti-cancer agents, especially in the blood-brain barrier. These results may explain a range of pharmacological interactions observed between various drugs in patients.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cited by
Daneman, R., & Prat, A. (2015) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a020412 · Cited by 3,437
Brain corticosteroid receptor balance in health and disease
de Kloet, E. R., Vreugdenhil, E., Oitzl, M. S., & Joëls, M. (1998) · Endocrine Reviews · doi:10.1210/edrv.19.3.0331 · Cited by 2,614
The Corticosteroid Receptor Hypothesis of Depression
Holsboer, F. (2000) · Neuropsychopharmacology · doi:10.1016/s0893-133x(00)00159-7 · Cited by 2,181
Neuroendocrine Regulation of Immunity
Webster, J. I., Tonelli, L., & Sternberg, E. M. (2002) · Annual Review of Immunology · doi:10.1146/annurev.immunol.20.082401.104914 · Cited by 957
van Helvoort, A., Smith, A. J., Sprong, H., Fritzsche, I., Schinkel, A. H., Borst, P., & van Meer, G. (1996) · Cell · doi:10.1016/s0092-8674(00)81370-7 · Cited by 855
Self-citation
Metadata
- Authors
- Schinkel, A. H., Wagenaar, E., van Deemter, L., Mol, C. A., & Borst, P.
- Venue
- Journal of Clinical Investigation
- Published
- 1995-10-01
- Volume
- 96
- Issue
- 4
- Pages
- 1698-1705
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2136564762
- Cited by
- 1,107
- References
- 0
- FWCI
- 15.47
- Type
- journal article
- Language
- en
- Open access
- bronze
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Absence of the mdr1a P-Glycoprotein in mice affects tissue distribution and pharmacokinetics of dexamethasone, digoxin, and cyclosporin A. https://app.cochat.ai/papers/10.1172/jci118214
- The paper
- Schinkel, A. H., Wagenaar, E., van Deemter, L., Mol, C. A., & Borst, P. (1995). Absence of the mdr1a P-Glycoprotein in mice affects tissue distribution and pharmacokinetics of dexamethasone, digoxin, and cyclosporin A. Journal of Clinical Investigation. https://doi.org/10.1172/jci118214
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
