Journal of clinical pharmacology最新文献

{"title":"Routine drug and food interactions during antihelminthic treatment of neurocysticercosis: a reason for the variable efficacy of albendazole and praziquantel?","authors":"Matthew L Romo,&nbsp;Arturo Carpio,&nbsp;Elizabeth A Kelvin","doi":"10.1002/jcph.269","DOIUrl":"https://doi.org/10.1002/jcph.269","url":null,"abstract":"<p><p>Neurocysticercosis (NC) or infection of the central nervous system with Taenia solium larvae is a leading cause of preventable seizures and epilepsy in endemic regions across the globe. Albendazole and praziquantel are commonly used antihelminthic agents to treat NC; however, viable cysts persist in the majority of patients, putting them at risk for future seizures and other neurological complications. Because of their pharmacokinetic profiles, albendazole and praziquantel have the potential to interact with many different drugs. During antihelminthic treatment, antiepileptic drugs and corticosteroids are commonly co-administered to manage seizures and cerebral edema; however, the most commonly used agents from these drug classes are known to significantly alter plasma concentrations of albendazole and praziquantel. The overarching issue with drug interactions during the treatment of NC is whether or not they have clinical relevance, as the plasma concentrations of albendazole and praziquantel have not been directly linked with eradication of viable cysts. Future studies should attempt to evaluate the validity of a causal relationship between antihelminthic plasma concentrations and outcomes so that drug interactions can be better understood and managed and so that treatment can be optimized. </p>","PeriodicalId":15536,"journal":{"name":"Journal of clinical pharmacology","volume":"54 4","pages":"361-7"},"PeriodicalIF":2.9,"publicationDate":"2014-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jcph.269","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32044394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of fludarabine on the pharmacokinetics of oral busulfan during pretransplant conditioning for hematopoietic stem cell transplantation.","authors":"Francine Attié de Castro,&nbsp;Vera Lucia Lanchote,&nbsp;Julio Cesar Voltarelli,&nbsp;Virgílio Antônio Rensi Colturato,&nbsp;Belinda Pinto Simões","doi":"10.1002/jcph.130","DOIUrl":"https://doi.org/10.1002/jcph.130","url":null,"abstract":"<p><p>This study evaluated the influence of fludarabine on the pharmacokinetics of busulfan administered orally to patients receiving a conditioning regimen for hematopoietic allogeneic stem cell transplantation (HSCT). Twenty-six patients treated with oral busulfan (1 mg/kg/6 h for 4 days) were divided into two groups according to the concomitant administration of fludarabine (n = 11; 30 mg/m(2) for 5 days) or subsequent administration of cyclophosphamide (n = 15; 60 mg/kg for 2 days). Serial blood samples were collected on Day 4 of busulfan administration. Plasma busulfan concentrations were determined by HPLC-UV and the pharmacokinetic parameters were calculated using the WinNonlin program. Patients concomitantly treated with fludarabine showed reduced apparent clearance of busulfan (110.5 mL/h/kg vs. 157.4 mL/h/kg) and higher AUC0-6 (area under the plasma concentrations vs. time curve) than patients subsequently treated with cyclophosphamide (7.9 µg h/mL vs. 5.7 µg h/mL). No association was observed between busulfan AUC0-6 and clinical evolution of the patients. Although plasma busulfan concentrations were higher in patients receiving concomitant fludarabine, myelosuppression-related toxicity was less frequent than in patients treated with busulfan and cyclophosphamide. The results suggest that patients treated with fludarabine should receive 30% lower busulfan doses during conditioning protocols for HSCT. </p>","PeriodicalId":15536,"journal":{"name":"Journal of clinical pharmacology","volume":"53 11","pages":"1205-11"},"PeriodicalIF":2.9,"publicationDate":"2013-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jcph.130","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31665486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of polymorphisms of the SLCO2B1 transporter gene on the pharmacokinetics of montelukast in humans.","authors":"Kyoung-Ah Kim,&nbsp;Hye-Mi Lee,&nbsp;Hyun-Jin Joo,&nbsp;In-Bae Park,&nbsp;Ji-Young Park","doi":"10.1002/jcph.144","DOIUrl":"https://doi.org/10.1002/jcph.144","url":null,"abstract":"<p><p>Montelukast, a leukotriene receptor antagonist, is a substrate of organic anion transporting OATP2B1 encoded by the SLCO2B1. We evaluated the effects of six non-synonymous (c.1175C>T, c.1457C>T, c.43C>T, c.935G>A, c.601G>A, and c.644A>T) polymorphisms and one promoter (g.-282G>A) polymorphism on the pharmacokinetics of montelukast. A single dose of 10 mg montelukast was administered in 24 healthy subjects. Its levels were measured up to 24 hours and a pharmacokinetic analysis was performed based on the SLCO2B1 polymorphisms. We did not encounter subjects with c.1175C>T, c.43C>T, or c.644A>T polymorphisms. The remaining SLCO2B1 polymorphisms did not affect plasma levels of montelukast, and pharmacokinetic parameters of montelukast did not differ among genotype groups. Oral clearance results were as follows: (1) 3.3 L/h for c.935GG, 3.0 L/h for c.935GA, and 3.5 L/h for c.935AA; (2) 3.4 L/h for c.1457CC, 2.9 L/h for c.1457CT, and 3.2 L/h for c.1457TT; (3) 3.2 L/h for c.601GG, 3.4 L/h for c.601GA, and 3.4 L/h for c.601AA; (4) 3.2 L/h for g.-282GG, 3.4 L/h for g.-282GA, and 3.2 L/h for g.-282AA. The findings suggest that SLCO2B1 polymorphisms do not affect the pharmacokinetics of montelukast and that SLCO2B1 polymorphisms appear to be a minor determinant of inter-individual variability of montelukast. </p>","PeriodicalId":15536,"journal":{"name":"Journal of clinical pharmacology","volume":"53 11","pages":"1186-93"},"PeriodicalIF":2.9,"publicationDate":"2013-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jcph.144","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31678991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of food on pharmacokinetics of zolpidem from fast dissolving sublingual zolpidem tartrate tablets.","authors":"David J Greenblatt,&nbsp;Jerold S Harmatz,&nbsp;Nikhilesh N Singh,&nbsp;Thomas Roth,&nbsp;Stephen C Harris,&nbsp;Ram P Kapil","doi":"10.1002/jcph.159","DOIUrl":"https://doi.org/10.1002/jcph.159","url":null,"abstract":"<p><p>Ingesting food can impact the pharmacokinetics of sedative-hypnotic drugs. A buffered zolpidem sublingual tablet (ZST) recently became available for the treatment of middle-of-the-night awakening. In this randomized, open-label, single-site study, the pharmacokinetic profile of ZST was evaluated when administered while fasting and following a standard high-fat meal (fed state). Healthy adults aged 18-64 years received a single morning dose of 3.5 mg ZST in the fed or fasting state. From 20 min to 3 h post-dose, zolpidem plasma levels were lower in the fed state compared to the fasting state. After 4 h post-dose (corresponding to \"morning wake time\"), higher zolpidem plasma levels were evident in the fed state. Area under the concentration-time curve (AUC) values for the 0-8 h interval were 160 ng/mL h in the fed state and 203 ng/mL h in the fasting state (P < .001). In the fed versus fasting states, Cmax was 32.0 ng/mL versus 57.3 ng/mL (P < .001), respectively, and Tmax was 3.0 h versus 0.92 h (P < .001), respectively. Together these data suggest that administration of ZST in the fed state is not optimal for maximizing the likelihood of therapeutic benefit and minimizing the probability of residual sedation. </p>","PeriodicalId":15536,"journal":{"name":"Journal of clinical pharmacology","volume":"53 11","pages":"1194-8"},"PeriodicalIF":2.9,"publicationDate":"2013-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jcph.159","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31652352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduced exposure variability of the CYP3A substrate simvastatin by dose individualization to CYP3A activity.","authors":"Felicitas Stoll,&nbsp;Jürgen Burhenne,&nbsp;Berthold Lausecker,&nbsp;Johanna Weiss,&nbsp;Torben Thomsen,&nbsp;Walter Emil Haefeli,&nbsp;Gerd Mikus","doi":"10.1002/jcph.161","DOIUrl":"https://doi.org/10.1002/jcph.161","url":null,"abstract":"<p><p>This study aimed to demonstrate that the dose of a CYP3A substrate (simvastatin) can be adapted individually on the basis of CYP3A activity as assessed by midazolam metabolic clearance. In 18 healthy participants individual CYP3A activity was quantified using midazolam metabolic clearance both alone and during CYP3A inhibition with 40 mg ritonavir. Thereafter, simvastatin acid exposure was determined after a simvastatin standard dose (40 mg) and doses adapted to individual CYP3A activity at baseline and during CYP3A inhibition. Interindividual variability of CYP3A activity and simvastatin acid AUC0-24 was large and both correlated (r(2)  = 0.745, P < .001). The adapted simvastatin doses ranged from 25 to 80 mg and their administration reduced simvastatin variability fivefold. Despite the low adapted simvastatin dose of 12 mg during CYP3A inhibition with ritonavir, exposure increased (point estimate of 4.2 [90% CI: 3.15-5.61]) probably caused by additional OATP1B1 inhibition. CYP3A activity-based dose adaptation can be used to reduce interindividual variability in simvastatin exposure. </p>","PeriodicalId":15536,"journal":{"name":"Journal of clinical pharmacology","volume":"53 11","pages":"1199-204"},"PeriodicalIF":2.9,"publicationDate":"2013-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jcph.161","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31652239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiple-dose, safety, pharmacokinetic, and pharmacodynamic study of sotatercept (ActRIIA-IgG1), a novel erythropoietic agent, in healthy postmenopausal women.","authors":"Matthew L Sherman,&nbsp;Niels G Borgstein,&nbsp;Louisa Mook,&nbsp;Dawn Wilson,&nbsp;Yijun Yang,&nbsp;Nianhang Chen,&nbsp;Ravindra Kumar,&nbsp;Kenneth Kim,&nbsp;Abderrahmane Laadem","doi":"10.1002/jcph.160","DOIUrl":"https://doi.org/10.1002/jcph.160","url":null,"abstract":"<p><p>Ligands of the transforming growth factor-beta superfamily and activin-receptor signaling play an important role in erythropoiesis. Sotatercept, an activin receptor type IIA (ActRIIA) ligand trap, is a novel, recombinant, fusion protein comprising the extracellular domain of human ActRIIA linked to the Fc portion of human immunoglobulin G1. Sotatercept, originally developed to increase bone mineral density, was noted to have robust effects on erythropoiesis. Here, we evaluated the safety, pharmacokinetic properties, and pharmacodynamic effects of sotatercept in 31 healthy postmenopausal women. Sotatercept was administered at dose level 0.1, 0.3, or 1 mg/kg every 28 days subcutaneously for up to four doses. Sotatercept was generally safe and well tolerated, and elicited clinically significant, dose-dependent increases in hemoglobin, hematocrit, and red blood cell counts that persisted for up to 4 months. The effect of sotatercept on hemoglobin was dose-limiting. Sotatercept also increased bone mineral density and biomarkers of bone formation. The sotatercept serum exposure-dose relationship was linear, with a mean terminal half-life of approximately 23 days. ActRIIA ligands are important regulators of erythrocyte production in healthy individuals. Clinical studies are ongoing to explore the potential of sotatercept to treat anemia and diseases of ineffective erythropoiesis as well as an agent to increase bone mineral density. </p>","PeriodicalId":15536,"journal":{"name":"Journal of clinical pharmacology","volume":"53 11","pages":"1121-30"},"PeriodicalIF":2.9,"publicationDate":"2013-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jcph.160","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31652426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics and pharmacodynamics of arterolane maleate following multiple oral doses in adult patients with P. falciparum malaria.","authors":"Anirudh Gautam,&nbsp;Tausif Ahmed,&nbsp;Pradeep Sharma,&nbsp;Brijesh Varshney,&nbsp;Monika Kothari,&nbsp;Nilanjan Saha,&nbsp;Arjun Roy,&nbsp;Joerg J Moehrle,&nbsp;Jyoti Paliwal","doi":"10.1177/0091270010385578","DOIUrl":"https://doi.org/10.1177/0091270010385578","url":null,"abstract":"<p><p>Arterolane (RBx 11160) maleate is a novel, rapidly acting synthetic trioxolane antimalarial compound being developed by Ranbaxy Research Laboratories (Haryana, India). It is presently under phase III in combination with piperaquine phosphate. The present work reports the relationship between pharmacokinetic (PK) parameter (AUC(0-8h) on day 0/day 6) and indices of pharmacodynamic (PD) response (50% parasite clearance [PC(50)], 90% parasite clearance [PC(90)], parasite clearance time [PCT], recrudescence) from a phase II, double-blind, multicenter, randomized, parallel-group, dose-ranging trial. Patients with acute uncomplicated P. falciparum malaria were randomized to 1 of 3 arterolane maleate (50, 100, and 200 mg) doses for 7 consecutive days. Plasma concentration data were available from 78, 76, and 75 patients receiving a 50-, 100-, and 200-mg dose, respectively. Based on PD modeling, its limitations and assumptions, minimum 150-mg dose arterolane maleate was recommended to optimize the probability of maximum therapeutic benefits for an adult. Doses higher than 100 mg are unlikely to reduce the probability of recrudescence. This study re-stresses the need of combining short and long-acting drugs to prevent resistance development and minimize recrudescence.</p>","PeriodicalId":15536,"journal":{"name":"Journal of clinical pharmacology","volume":"51 11","pages":"1519-28"},"PeriodicalIF":2.9,"publicationDate":"2011-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/0091270010385578","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29526805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of yogurt and applesauce on the oral bioavailability of nilotinib in healthy volunteers.","authors":"Ophelia Q P Yin,&nbsp;Marc Rudoltz,&nbsp;Ivana Galetic,&nbsp;Jeiry Filian,&nbsp;Arun Krishna,&nbsp;Wei Zhou,&nbsp;Joseph Custodio,&nbsp;Georg Golor,&nbsp;Horst Schran","doi":"10.1177/0091270010384116","DOIUrl":"https://doi.org/10.1177/0091270010384116","url":null,"abstract":"<p><p>Nilotinib, a potent orally bioavailable BCR-ABL tyrosine kinase inhibitor, is currently available as a hard gelatin capsule that must be swallowed whole. For patients who may have difficulty swallowing the intact capsule, an alternative mode of administration is desirable. The authors compared the bioavailability of nilotinib from the following administrations in 48 healthy subjects: (1) 400 mg nilotinib given as two 200-mg nilotinib intact capsules; (2) contents of two 200-mg nilotinib capsules, each capsule dispersed in 1 teaspoon of nonfat plain yogurt; and (3) contents of two 200-mg nilotinib capsules, each capsule dispersed in 1 teaspoon of applesauce. Nilotinib absorption was modestly increased following the administration of nilotinib dispersed in yogurt. The geometric mean ratios (90% confidence intervals) for nilotinib C(max), AUC(0-tlast), and AUC(0-inf) were 1.31 (1.22-1.41), 1.11 (1.05-1.16), and 1.08 (1.02-1.15), respectively. Administration of nilotinib dispersed in applesauce showed equivalent bioavailability compared with administration of nilotinib as intact capsules. The geometric mean ratios (90% confidence intervals) for nilotinib C(max), AUC(0-tlast), and AUC(0-inf) were 0.95 (0.88-1.02), 0.99 (0.94-1.04), and 0.97 (0.90-1.03), respectively. Each treatment was well tolerated in the study subjects. The data support a feasible alternative method of nilotinib administration; each capsule's contents may be dispersed in 1 teaspoon of applesauce and taken immediately.</p>","PeriodicalId":15536,"journal":{"name":"Journal of clinical pharmacology","volume":"51 11","pages":"1580-6"},"PeriodicalIF":2.9,"publicationDate":"2011-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/0091270010384116","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29969902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A review of psychophysiological stressors on pharmacokinetics.","authors":"Henry Tao Peng,&nbsp;Bob Cheung","doi":"10.1177/0091270010393344","DOIUrl":"https://doi.org/10.1177/0091270010393344","url":null,"abstract":"<p><p>We conducted a comprehensive literature review on the effects of psychophysiological stressors on the pharmacokinetics of drugs commonly used by the Canadian Forces. These stressors may change the physiological status of an individual and subsequently may alter the drug's pharmacokinetics. The effects of isolated physical activities on pharmacokinetics have been well documented. However, the findings are inconsistent due to variations in the intensity and duration of the activity, and the routes and timing of drug administration. The effects of other environmental stressors, such as temperature extremes, hypobaric, hyperbaric, hyperoxic conditions, and the effects of multiple stressors are less well known. There are limited studies describing the effects of psychological stressors on drug pharmacokinetics. Further studies are necessary to understand the clinical implications of pharmacokinetic changes. We also discussed the advantage of using a physiologically based pharmacokinetic model to predict the effects of a single or multiple stressors.</p>","PeriodicalId":15536,"journal":{"name":"Journal of clinical pharmacology","volume":"51 11","pages":"1499-518"},"PeriodicalIF":2.9,"publicationDate":"2011-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/0091270010393344","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29618272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The seduction of biomarkers in the practice of medicine and the tyranny of power in the drug approval process: lessons from niacin.","authors":"David F Lehmann,&nbsp;Daniel S Sitar","doi":"10.1177/0091270011420253","DOIUrl":"https://doi.org/10.1177/0091270011420253","url":null,"abstract":"T practice of clinical medicine continues to evolve. The proper use of technology has undoubtedly improved the longevity and quality of life of patients throughout the world. However, overreliance on and overinterpretation of selected surrogates (biomarkers) for disease improvement, subsequent to therapeutic interventions, threaten to supplant a focus on complete history taking and thorough physical examination of the patient. This more comprehensive approach, although ideal, may not be operational to an extent sufficient to relegate the interpretation of biomarkers to a supportive role as one of many factors guiding optimization of therapeutic interventions. Several recent developments have likely contributed to this trend. Time pressure on all physicians, but especially those in primary care, may abrogate the due diligence necessary to adequately gain a complete picture of illness. Although overall physicianpatient communication seems not to be negatively impacted by the availability of computers in examination rooms, the instant availability of laboratory tests at the time of the patient visit may seduce both the patient and the physician to emphasize communications on questions such as “Doc, what do my numbers look like today?” to the exclusion of other pertinent issues. Lastly, the intensity of direct-to-consumer advertising, complemented by pharmaceutical detailing techniques, reinforces a natural human tendency to focus on numerical parameters that can be most directly impacted by therapeutic interventions. The clinical trial NCT00120289, a study to determine whether adding niacin to statin therapy would reduce the incidence of vascular events, is the most recent example that further informs the proper role regarding the use of biomarkers in clinical medicine. This study was stopped 18 months early because there was no possibility that adding extended-release niacin to either the simvastatin or atorvastatin treatment arms would achieve the desired clinical endpoints of reducing cardiovascular disease and because it unexpectedly documented a small unexplained increase in ischemic strokes in the high-dose niacin group, despite achieving marked improvements in serum triglycerides and high-density lipoprotein (HDL). Niacin’s lack of impact on clinically relevant cardiovascular outcomes in this clinical trial, despite improvement in both surrogate biomarkers, is consistent with and extends observations from previous reports of the lack of benefit on cardiovascular outcomes in patients with type 2 diabetes when fenofibrate is added to simvastatin, despite a significant reduction in triglycerides. Careful interpretation of these developments may clarify the singular importance of lowering low-density lipoprotein (LDL) cholesterol, according to our current understanding of the mechanism of the lipogenesis-cellular signaling continuum as it relates to the development of drug targets. Statin drugs are unquestionably effective in improving cardiovasc","PeriodicalId":15536,"journal":{"name":"Journal of clinical pharmacology","volume":"51 11","pages":"1496-8"},"PeriodicalIF":2.9,"publicationDate":"2011-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/0091270011420253","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30062189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}