Author Interviews, Geriatrics, Pharmacology / 13.05.2016

MedicalResearch.com Interview with: Leigh Purvis, MPA Director of Health Services Research AARP Public Policy Institute MedicalResearch.com Editor’s Note: The May AARP Bulletin has a important article “Black Market Meds Are Flooding the Nation’s Pharmacies And Hospitals” by Joe Eaton, discussing the growing problem of counterfeit medications entering the US pharmaceutical supply chain. Ms. Leigh Purvis of the AARP Policy Institute discussed this important issue for the readers of MedicalResearch.com. Ms. Purvis’ areas of expertise include prescription drug pricing, biologic drugs, and Medicare prescription drug coverage.  MedicalResearch.com: Is pharmaceutical theft and fraud a new or growing problem? Ms. Purvis: I think it’s safe to say that pharmaceutical theft is a growing problem. Skyrocketing prices have made pharmaceuticals a lucrative target for criminals. Trucks transporting pharmaceuticals are a common target, although some thieves have stolen prescription drugs directly from manufacturers’ warehouses. Pharmaceutical fraud is also a growing concern. FDA does a great deal to ensure the safety of US pharmaceuticals. However, problems can still arise, particularly when people purchase drugs online. (more…)
Author Interviews, Cost of Health Care, University of Pittsburgh / 03.06.2015

Julie M. Donohue, Ph.D. Associate professor and Vice Chair for Research Graduate School of Public Health Department of Health Policy and Management University of PittsburghMedicalResearch.com Interview with: Julie M. Donohue, Ph.D. Associate professor and Vice Chair for Research Graduate School of Public Health Department of Health Policy and Management University of Pittsburgh Medical Research: What is the background for this study? What are the main findings? Dr. Donohue: We looked at data on medication use from January through September 2014 on 1 million Affordable Care Act-established marketplace insurance plan enrollees. Our analysis found that among people who enrolled in individual marketplaces, those who enrolled earlier were older and used more medication than later enrollees. Marketplace enrollees, as a whole, had lower average drug spending per person and were less likely to use most medication classes than patients enrolled in employer-sponsored health insurance. However, marketplace enrollees were much more likely to use medicines for hepatitis C and for HIV, which is particularly important given the general concerns about the rising costs of these medications for consumers. (more…)
Author Interviews, PNAS, Statins / 04.03.2015

Professor Andrew W. Munro FRSC FSB Professor of Molecular Enzymology Manchester Institute of Biotechnology Faculty of Life Sciences University of Manchester Manchester UKMedicalResearch.com Interview with: Professor Andrew W. Munro FRSC FSB Professor of Molecular Enzymology Manchester Institute of Biotechnology Faculty of Life Sciences University of Manchester Manchester UK MedicalResearch: What is the background for this study? What are the main findings? Dr. Munro: Statins are blockbuster drugs that inhibit the key enzyme in cholesterol synthesis: 3-beta-hydroxymethylglutaryl CoA reductase (HMG-CoA reductase), which catalyzes the rate-limiting step in the biosynthesis of cholesterol. As a consequence, statin drugs reduce levels of low-density lipoprotein (LDL-) cholesterol, are effective against hypercholesterolemia and reduce the risk of atherosclerosis and heart attack. One of the major statin drugs is pravastatin, which is derived from a fungal natural product called compactin. The process of conversion of compactin into pravastatin involves the use of an oxygen-inserting enzyme called a cytochrome P450 (or P450), which catalyzes the hydroxylation of compactin to form pravastatin. In order to produce a more cost-efficient and streamlined route to pravastatin production, our teams from the University of Manchester (UK) and DSM (Delft, The Netherlands) developed a single-step process for pravastatin production. This process involved harnessing the productive efficiency of an industrial strain of the beta-lactam (penicillin-type) antibiotic producing fungus Penicillium chrysogenum. The beta-lactam antibiotic genes were deleted from this organism, and replaced by those encoding for compactin biosynthesis (transferred from a different Penicillium species). This led to high level production of compactin, but also to substantial formation of a partially degraded (deacylated) form. To get around this problem and in order to further improve compactin production, the enzyme responsible for the deacylation (an esterase) was identified and the gene encoding this activity was deleted from the production strain. The final stages of development of the novel, one-step pravastatin production process involved the identification of a suitable P450 enzyme that could catalyze the required hydroxylation of compactin. A bacterial P450 was identified that catalyzed hydroxylation at the correct position on the compactin molecule. However, the stereoselectivity of the reaction was in favour of the incorrect isomer – forming predominantly epi-pravastatin over the desired pravastatin. This was addressed by mutagenesis of the P450 – ultimately leading to a variant (named P450Prava) that hydroxylated compactin with the required stereoselectivity to make pravastatin in large amounts. Determination of the structure of P450Prava in both the substrate-free and compactin-bound forms revealed the conformational changes that underpinned the conversion of the P450 enzyme to a pravastatin synthase. The expression of P450Prava in a compactin-producing strain of P. chrysogenum enabled pravastatin production at over 6 g/L in a fed-batch fermentation process, facilitating an efficient, single-step route to high yield generation of pravastatin. (more…)