Top-selling Drugs Research Articles

Can Physicians Keep Up? A Quantification of New Information on the Top 25 Drugs from 2000 to 2003

ABSTRACTThe body of knowledge regarding pharmaceutical products is dynamic and growing. Physicians have available to them a number of information sources for drug-related decision making in their practice. Historical and recent publications present medical literature and conferences as sources for information on pharmaceutical products. While historical reports have detailed large volumes of information being disseminated through these sources, no recent work has evaluated the level of information for top-selling drugs provided through these outlets. This study quantified the amount of publications and conference presentations for the 25 top-selling pharmaceutical products and poses questions about practitioners' ability to keep abreast of the changing knowledge base. We found that for each of the top 25 branded outpatient drugs in each year studied an average of 214 scholarly articles were published in literature indexed in Medline® and International Pharmaceutical Abstracts and 158 papers or posters wer...

Going global in R&D.

Economics and politics are making offshoring an increasingly attractive option for biobusinesses

Structure-based identification of binding sites, native ligands and potential inhibitors for G-protein coupled receptors.

G-protein coupled receptors (GPCRs) are the largest family of cell-surface receptors involved in signal transmission. Drugs associated with GPCRs represent more than one fourth of the 100 top-selling drugs and are the targets of more than half of the current therapeutic agents on the market. Our methodology based on the internal coordinate mechanics (ICM) program can accurately identify the ligand-binding pocket in the currently available crystal structures of seven transmembrane (7TM) proteins [bacteriorhodopsin (BR) and bovine rhodopsin (bRho)]. The binding geometry of the ligand can be accurately predicted by ICM flexible docking with and without the loop regions, a useful finding for GPCR docking because the transmembrane regions are easier to model. We also demonstrate that the native ligand can be identified by flexible docking and scoring in 1.5% and 0.2% (for bRho and BR, respectively) of the best scoring compounds from two different types of compound database. The same procedure can be applied to the database of available chemicals to identify specific GPCR binders. Finally, we demonstrate that even if the sidechain positions in the bRho binding pocket are entirely wrong, their correct conformation can be fully restored with high accuracy (0.28 A) through the ICM global optimization with and without the ligand present. These binding site adjustments are critical for flexible docking of new ligands to known structures or for docking to GPCR homology models. The ICM docking method has the potential to be used to "de-orphanize" orphan GPCRs (oGPCRs) and to identify antagonists-agonists for GPCRs if an accurate model (experimentally and computationally validated) of the structure has been constructed or when future crystal structures are determined.

In Brief

Personalization of drug therapies, enabling the prevention of adverse drug reactions (ADRs), could be made possible with pharmacogenomics. A study led by scientists at the University of California (UCSF, San Francisco, CA, USA) is the first systematic assessment of the potential of pharmacogenomics [J. Am. Med. Assoc. (2001) 286, 2270–2279]. To assess the possible contribution of genetic variability to ADRs, the researchers combined a study of variant alleles for drug-metabolizing enzymes, with a study of ADRs. 59% of the drugs cited in the ADR study are metabolized by at least one enzyme that has a naturally occurring variant associated with poor metabolism. However, only 22% of randomly selected drugs sold in the US, and 7% of randomly selected top-selling American drugs, are metabolized by enzymes with this genetic variability. ‘Our study confirms the powerful potential of genetic information to improve drug therapies, but it also emphasizes the importance of considering how genetics will affect both health care practice and the public,’ said Kathryn A. Phillips, lead author on the report and UCSF associate professor of health economics and health services research. ‘In the future,’ the authors conclude, ‘...we may all carry a “gene chip assay report” that contains our unique genetic profile that would be consulted before drugs are prescribed.’ However, the clash between pharmacogenomic and economic sense might raise problems. For example, although small racial groups have genetic variants making them vulnerable to some drugs, drug companies might not think it worthwhile to develop alternative drugs for such a small market. Further problems to implementation include inadequate training for clinicians and inadequate funding for genotyping. S de B

Toward designing drug-like libraries: a novel computational approach for prediction of drug feasibility of compounds.

Prediction of the degree of drug-like character in small molecules is of great industrial interest. The major barrier, however, is the lack of a definition for drug-like character. We used the concept of the multilevel chemical compatibility (MLCC) between a compound and a drug library as a measure of the drug-like character of a compound. The rationale is that the local chemical environment of each atom or group of atoms in a compound largely contributes to the stability, toxicity, and metabolism in vivo. A systematic comparison of the local environments within a compound and those within the existing drugs provides a basis for determining whether and how much a compound is drug-like. We applied the MLCC calculations to four test sets: top selling drugs, compounds under biological testing prior to the preclinical test, anticancer drugs, and compounds known to have poor drug-like character. The following conclusions were obtained: (1) A convergent number of unique local structure types were found in the analysis of the library of the existing drugs. It suggests that the current drug library contains about 80% of all the viable types; therefore, discovery of a drug with new local structures is only an event of relatively small probability. (2) The method is highly selective in discerning drug-like compounds: most of the top drugs are predicted to be drug-like, about one-quarter of the biological testing compounds are drug-like, and about one-fifth of the anticancer drugs are drug-like. (3) The method also correctly predicted that none of the known problematic compounds are drug-like. (4) The method is fast enough for computational screening of virtual combinatorial chemistry libraries and databases of available compounds.

COUNTING ON CHIRAL DRUGS

Chiral drugs continue to be a significant force in the global pharmaceutical market. Worldwide sales of single-enantiomer drugs surged 21% in 1997 over 1996 to almost $90 billion, according to analysts at the consulting firm Technology Catalysts International (TCI). Richard L. DiCicco, president of the Falls Church, Va., company, attributes this strong showing to advances in enantiomeric cardiovascular, central nervous system, antiviral, and anticancer drugs. Despite the double digits, the 1997 growth rate for chiral drugs was not a record. We believe one of the reasons for this smaller growth, 20.6% in 1997 versus 27% [in the past five years], is the strength of U.S. says Sujuan Ba, director of chiral chemistry consulting services at TCI. Many pharmaceutical companies will have to convert their international sales back to dollars, which lose some value due to the exchange rate. To show the importance of single-enantiomer drugs today, Ba measures their appearance among the top-selling drugs. ...

Do open formularies increase access to clinically useful drugs?

Before 1990 many state Medicaid programs maintained "restrictive" formularies, which denied reimbursement for unlisted prescription drugs. This type of formulary has been criticized for denying important medications to poor, medically needy persons. As part of the Omnibus Budget Reconciliation Act of 1990, restrictive formularies in Medicaid programs were disallowed. Based on research into the 200 top-selling prescription drugs in the United States, we conclude that eliminating Medicaid restrictive formularies improved access to a subset of the 200 best sellers, but that the majority of these products offered only questionable or no additional therapeutic benefit.

Warning to otolaryngologists using local anesthetics containing epinephrine. Potential serious reaction occurring in patients treated with beta-adrenergic receptor blockers.

In the practice of otolaryngology, epinephrine is frequently administered to patients in combination with local anesthetics. If epinephrine is administered to patients who are taking β -adrenergic blockers, it is possible to produce a hypertensive crisis that is immediately followed by cardiac slowing and possibly cardiac standstill. Two publications 1,2 describe the risk of this serious interaction that can occur in patients who are given local anesthetic solutions containing epinephrine while they are being treated with β -adrenergic blocking drugs such as propranolol hydrochloride. Foster and Aston 1 reported six cases in which the interaction occurred in patients undergoing either blepharoplasty or a combination of rhytidectomy and blepharoplasty. The β -adrenergic blockers are being used for the treatment of many different conditions. Because of this widespread use, they are one of the top-selling drugs in the United States and may have even surpassed diazepam in use. β -Adrenergic receptors are

Oxytocin release by infused prostaglandin.

<h3>Background:</h3> Whether drug promotion helps or hinders appropriate prescribing by physicians is debated. This study examines the most heavily promoted drugs and the therapeutic value of those drugs to help determine whether doctors should be using promotional material to inform themselves about drugs. <h3>Methods:</h3> Lists were constructed of the 50 most heavily promoted drugs (amount of money spent on journal advertisements and visits by sales representatives) and the 50 top-selling drugs (by dollar value) for 2013, 2014 and 2015. Therapeutic gain was determined by examining ratings from the Patented Medicine Prices Review Board and the French drug bulletin Prescrire International and was categorized as major, moderate or little to none. For each of the 3 years, the number of drugs in the 3 therapeutic categories for drugs in both groups was compared. The amount and proportion of money spent on promotion for drugs in each of the 3 therapeutic categories for the 3 years was also determined. <h3>Results:</h3> Therapeutic ratings were available for 42 of 79 of the most heavily promoted drugs over the 3 years and for 40 of 61 of the top-selling drugs. Nearly all the money spent on promotion in each of the 3 years went to drugs with little to no therapeutic gain. The distribution of therapeutic gain for drugs in both groups was statistically significantly different only in 2013 (<i>p</i> = 0.04). <h3>Interpretation:</h3> Most of the money spent on promotion went to drugs that offer little to no therapeutic gain. This result calls into question whether doctors should read journal advertisements or see sales representatives to acquire information about important medical therapies.