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Cyclosporine A, but Not Tacrolimus, Shows Relevant Inhibition of Organic Anion-Transporting Protein 1B1-Mediated Transport of Atorvastatin [ARTICLES]

The aim of this study was to investigate the potential of calcineurin inhibitors [cyclosporine A (CsA) and tacrolimus (Tac)] to inhibit cellular uptake of atorvastatin mediated by the liver-specific organic anion-transporting polypeptide 1B1 (OATP1B1) in vitro. Patients with solid organ transplants are frequently treated with HMG-CoA reductase inhibitors (statins). CsA increases atorvastatin systemic exposure severalfold, an effect not observed with Tac. The effect of CsA and Tac on atorvastatin transport via OATP1B1 was investigated in transfected human embryonic kidney 293 cells. An in vitro-in vivo extrapolation (IVIVE) was performed to estimate the clinical potential for CsA and Tac to inhibit OATP1B1-mediated transport. CsA inhibited OATP1B1-mediated uptake of atorvastatin approximately 90-fold more efficiently than Tac, with half-maximal inhibitory concentration (IC₅₀) values of 0.021 ± 0.004 and 1.99 ± 0.42 µM, respectively. Coincubation compared with preincubation with CsA showed a 20-fold lower inhibitory capacity, with an IC₅₀ value of 0.47 ± 0.34 µM. The IVIVE showed that clinically obtainable concentrations of CsA, but not Tac, inhibit OATP1B1 transport of atorvastatin. CsA inhibition ranged from 28 to 77% within a dosing interval, whereas it was less than 1% for Tac, considering free concentrations and assuming competitive inhibition. This does not fully explain the clinically observed interaction with CsA, suggesting that a more complex inhibitory mechanism may be present. This is also supported by the decreased IC₅₀ value of CsA after preincubation. This study provides evidence that OATP1B1 inhibition is a relevant mechanism for the interaction observed between CsA and atorvastatin.

H.I.V. Prevention Gel Hits Snag: Money
Donors have not yet committed enough money for studies needed to confirm a promising South African trial of a microbicide and to get the product to women. (Source: NYT Health)

Clinical Trials Update: Aug. 24, 2010 (HealthDay)
HealthDay - (HealthDay News) -- Here are the latest clinical trials, courtesy of ClinicalConnection.com:

EMS safety perceptions vary widely
PITTSBURGH, Sept. 4 (UPI) -- Safety perceptions among U.S. and Canadian emergency medical services agencies vary widely, researchers found. Emergency medical services - Health - Public Health and Safety - Emergency Services - Medical (Source: Health News - UPI.com)

New Discovery Could Pave The Way For Identification Of Rogue CFC Release
A new discovery by scientists at the Universities of East Anglia and Frankfurt could make it possible in future to identify the source of banned CFCs that are probably still being released into the atmosphere. Using mass spectrometers, the researchers analysed air samples collected in the stratosphere by balloons belonging to the French space agency, the Centre National d'Etudes Spatiales (CNES). They discovered the largest chlorine isotope enrichment ever found in nature. CFCs were banned in most countries because of their depletion of the ozone layer... (Source: Health News from Medical News Today)div id=medwormpbiMedWorm Message:/i/b Register forba href=http://www.medmatcha.com target =_selfMedMatcha, MedWorm's medical advertising network/a/b, and receive $5 free advertising./p/div

Chemical In Widely Consumed Foods Linked To Skin Cancer
The September cover story of the nation's leading cancer journal, Cancer Research, features a new study from The Hormel Institute, University of Minnesota, that links capsaicin, a component of chili peppers, to skin cancer. While the molecular mechanisms of the cancer-promoting effects of capsaicin are not clear and remain controversial, The Hormel Institute has shown a definite connection to formation of skin cancer through various laboratory studies... (Source: Health News from Medical News Today)

Video: The Best and Worst Burger Joints
A recent survey of Consumer Reports' subscribers finds that lesser-known fast food chains such as In-N-Out and Five Guys have better tasting hamburgers than McDonald's or Burger King. Erica Hill reports. (Source: Health News: CBSNews.com)

Eggs and salmonella contamination
Factors to keep in mind, whether buying eggs from big commercial suppliers or farmers markets or gathering from a backyard coop.As the scope of the nationwide salmonella outbreak expanded late last month, farmers market vendors reported rushes on locally produced eggs and people with backyard flocks were sitting smug. (Source: L.A. Times - Health)