ArticleBritish journal of pharmacology2010
Positron emission tomography imaging of tissue P-glycoprotein activity during pregnancy in the non-human primate.
Article in British journal of pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 37 citations in OpenAlex.
- Functioning of P-Glycoprotein during Pregnancy in Rabbits.Bulletin of experimental biology and medicine · 2023Article
- Maternal and Fetal Expression of ATP-Binding Cassette and Solute Carrier Transporters Involved in the Brain Disposition of Drugs.Advances in experimental medicine and biology · 2023Article
- An update on expression and function of P-gp/ABCB1 and BCRP/ABCG2 in the placenta and fetus.Expert opinion on drug metabolism & toxicology · 2018Review
- Critical Issues and Optimized Practices in Quantification of Protein Abundance Level to Determine Interindividual Variability in DMET Proteins by LC-MS/MS Proteomics.Clinical pharmacology and therapeutics · 2018Review
- Drug Transport at the Brain and Endothelial Dysfunction in Preeclampsia: Implications and Perspectives.Frontiers in physiology · 2018Article
- Mechanisms and the clinical relevance of complex drug-drug interactions.Clinical pharmacology : advances and applications · 2018Review
- Cardiovascular Ion Channel Inhibitor Drug-Drug Interactions with P-glycoprotein.The AAPS journal · 2017Review
- Placental ABC Transporters: Biological Impact and Pharmaceutical Significance.Pharmaceutical research · 2016Review
- Bioluminescent imaging of ABCG2 efflux activity at the blood-placenta barrier.Scientific reports · 2016Article
- Disrupting P-glycoprotein function in clinical settings: what can we learn from the fundamental aspects of this transporter?American journal of cancer research · 2016Review
- The cerebral circulation during pregnancy: adapting to preserve normalcy.Physiology (Bethesda, Md.) · 2015Review
- Using positron emission tomography to study transporter-mediated drug-drug interactions in tissues.Clinical pharmacology and therapeutics · 2014Review
- Activity of P-Glycoprotein, a β-Amyloid Transporter at the Blood-Brain Barrier, Is Compromised in Patients with Mild Alzheimer Disease.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2014Article
- An analysis of whole body tracer kinetics in dynamic PET studies with application to image-based blood input function extraction.IEEE transactions on medical imaging · 2014Article
- Modeling cyclosporine A inhibition of the distribution of a P-glycoprotein PET ligand, 11C-verapamil, into the maternal brain and fetal liver of the pregnant nonhuman primate: impact of tissue blood flow and site of inhibition.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2013Article
- PET and SPECT radiotracers to assess function and expression of ABC transporters in vivo.Current drug metabolism · 2011Review
- Regional P-glycoprotein activity and inhibition at the human blood-brain barrier as imaged by positron emission tomography.Clinical pharmacology and therapeutics · 2010Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
background and purposeChanges in tissue P-glycoprotein (P-gp) activity during pregnancy could affect the pharmacokinetics and thus the efficacy and toxicity of many drugs. Therefore, using positron emission tomography (PET) imaging, we tested whether gestational age affects tissue P-gp activity in the pregnant non-human primate, Macaca nemestrina. EXPERIMENTAL APPROACH: Mid-gestational (day 75 +/- 13, n= 7) and late-gestational (day 150 +/- 10, n= 5) age macaques were imaged after administration of a prototypic P-gp substrate, (11)C-verapamil (13.7-75.4 MBq.kg(-1)), before and during intravenous infusion of a P-gp inhibitor, cyclosporin A (CsA) (12 or 24 mg.kg(-1).h(-1)). Accumulation of radioactivity in the fetal liver served as a reporter of placental P-gp activity. P-gp activity was expressed as CsA-induced percent change in the ratio of the area (0-9 min) under the (11)C-radioactivity concentration-time curve in the tissue (AUC(tissue)) to that in the maternal plasma (AUC(plasma)). KEY
resultsThe CsA-induced change in AUC(fetal liver)/AUC(maternal)(plasma) of (11)C-radioactivity significantly increased from mid- (35 +/- 25%) to late gestation (125 +/- 66%). Likewise, the CsA-induced change in AUC(maternal brain)/AUC(plasma) increased from mid- (172 +/- 80%) to late gestation (337 +/- 148%). The AUC ratio for the other maternal tissues was not significantly affected. Neither the CsA blood concentrations nor the level of circulating (11)C-verapamil metabolites were significantly affected by gestational age. CONCLUSIONS AND IMPLICATIONS: P-gp activity at the blood-brain barrier and the placental barrier in the macaque increased with gestational age. If replicated in humans, the exposure of the fetus and maternal brain to P-gp substrate drugs, and therefore their efficacy and toxicity, will change during pregnancy.
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