ArticlePharmaceutical research2004
In situ transport of vinblastine and selected P-glycoprotein substrates: implications for drug-drug interactions at the mouse blood-brain barrier.
Article in Pharmaceutical research, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 33 citations in OpenAlex.
- Colchicine intoxication in familial Mediterranean fever patients using clarithromycin for the treatment of Helicobacter pylori: a series of six patients.Rheumatology international · 2018Article
- A polyspecific drug/proton antiporter mediates diphenhydramine and clonidine transport at the mouse blood-retinal barrier.British journal of pharmacology · 2015Article
- Impact of P-glycoprotein at the blood-brain barrier on the uptake of heroin and its main metabolites: behavioral effects and consequences on the transcriptional responses and reinforcing properties.Psychopharmacology · 2014Article
- Cyclosporine-inhibitable blood-brain barrier drug transport influences clinical morphine pharmacodynamics.Anesthesiology · 2013Article
- Changes in the brain accumulation of glucocorticoids in abcb1a-deficient CF-1 mice.Journal of neuroendocrinology · 2012Article
- A new in situ brain perfusion flow correction method for lipophilic drugs based on the pH-dependent Crone-Renkin equation.Pharmaceutical research · 2011Article
- Automated radiosynthesis of [11C]morphine for clinical investigation.Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine · 2011Article
- Physicochemical selectivity of the BBB microenvironment governing passive diffusion--matching with a porcine brain lipid extract artificial membrane permeability model.Pharmaceutical research · 2011Article
- P-glycoprotein deficient mouse in situ blood-brain barrier permeability and its prediction using an in combo PAMPA model.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2009Article
- Steroid hormones affect binding of the sigma ligand 11C-SA4503 in tumour cells and tumour-bearing rats.European journal of nuclear medicine and molecular imaging · 2009Article
- A revised role for P-glycoprotein in the brain distribution of dexamethasone, cortisol, and corticosterone in wild-type and ABCB1A/B-deficient mice.Endocrinology · 2008Article
- Pharmacokinetic consequences of active drug efflux at the blood-brain barrier.Pharmaceutical research · 2006Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo study the intrinsic parameters of P-glycoprotein (P-gp) transport and drug-drug interactions at the blood-brain barrier (BBB), as few quantitative in vivo data are available. These parameters could be invaluable for comparing models and predicting the in vivo implications of in vitro studies.
methodsThe brains of P-gp-deficient mice mdr1a(-/-) and wild-type mice were perfused in situ using a wide range of colchicine, morphine, and vinblastine concentrations. The difference between the uptake by the wild-type and P-gp-deficient mice gave the P-gp-linked apparent transport at the BBB. Drug-drug interactions were examined using vinblastine and compounds that bind to P-gp sites (verapamil, progesterone, PSC833) other than the vinblastine site to take into account the multispecific drug P-gp recognition.
resultsP-gp limited the brain uptake of morphine and colchicine in a concentration-independent way up to 2 mM. In contrast, vinblastine inhibited its own P-gp transport with an IC50 of approximately 56 microM and a Hill coefficient of approximately 4. The vinblastine efflux by P-gp was described by a Km at 16 microM and a maximal efflux velocity, Jmax, of approximately 8 pmol s(-1) g(-1) of brain. Similarly, vinblastine brain transport was increased by inhibiting P-gp as shown by the IC50 ranking, which was PSC833 < verapamil < vinblastine < progesterone.
conclusionsP-gp is responsible for both capacity-limited and -unlimited transport of P-gp substrates at the mouse BBB. In situ perfusion of mdr1a(-/-) and wild-type mouse brains could be used to predict drug-drug interactions for P-gp at the mouse BBB.
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