Lei Dong, L. Zhu, Bao-jie Xie, Ji-bin Li, Tao Ding, Yun-fa Jiang, Zhong-Ning Zhu
To compare the effectiveness of different taxane‐containing regimens and to identify the best strategy for the treatment of human epidermal growth factor receptor 2 (HER2)‐negative metastatic breast cancer (MBC).
{"title":"Comparative Effectiveness of Taxane‐Containing Regimens for Treatment of HER2‐Negative Metastatic Breast Cancer: A Network Meta‐analysis","authors":"Lei Dong, L. Zhu, Bao-jie Xie, Ji-bin Li, Tao Ding, Yun-fa Jiang, Zhong-Ning Zhu","doi":"10.1002/phar.2344","DOIUrl":"https://doi.org/10.1002/phar.2344","url":null,"abstract":"To compare the effectiveness of different taxane‐containing regimens and to identify the best strategy for the treatment of human epidermal growth factor receptor 2 (HER2)‐negative metastatic breast cancer (MBC).","PeriodicalId":19812,"journal":{"name":"Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87184941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Nuland, A. Bergman, H. Rosing, N. Vries, A. Huitema, J. Beijnen
Enzalutamide is an oral agent for the treatment of metastatic castration‐resistant prostate cancer (mCRPC); N‐desmethyl enzalutamide is its active metabolite, which has clinically relevant anti‐androgen capacities similar to enzalutamide, and carboxylic acid enzalutamide is an inactive metabolite. The aim of our study was to investigate the relationship between enzalutamide and N‐desmethyl enzalutamide exposure and treatment response in a real‐world cohort of patients with mCRPC.
{"title":"Exposure‐Response Assessment of Enzalutamide and Its Major Metabolites in a Real‐World Cohort of Patients with Metastatic Castration‐Resistant Prostate Cancer","authors":"M. Nuland, A. Bergman, H. Rosing, N. Vries, A. Huitema, J. Beijnen","doi":"10.1002/phar.2339","DOIUrl":"https://doi.org/10.1002/phar.2339","url":null,"abstract":"Enzalutamide is an oral agent for the treatment of metastatic castration‐resistant prostate cancer (mCRPC); N‐desmethyl enzalutamide is its active metabolite, which has clinically relevant anti‐androgen capacities similar to enzalutamide, and carboxylic acid enzalutamide is an inactive metabolite. The aim of our study was to investigate the relationship between enzalutamide and N‐desmethyl enzalutamide exposure and treatment response in a real‐world cohort of patients with mCRPC.","PeriodicalId":19812,"journal":{"name":"Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79019867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Libby A Orzel, Erik E. Abel, D. Blais, Tzu‐Fei Wang, K. Porter, P. Burcham
Bivalirudin, a direct thrombin inhibitor, is a treatment option for the management of heparin‐induced thrombocytopenia (HIT) and other coagulation disorders. To date, no published studies have identified patients at risk for or the consequence of subtherapeutic bivalirudin therapy.
{"title":"Risk Factors and Outcomes Associated with Prolonged Subtherapeutic Anticoagulation with Bivalirudin: A Retrospective Cohort Study","authors":"Libby A Orzel, Erik E. Abel, D. Blais, Tzu‐Fei Wang, K. Porter, P. Burcham","doi":"10.1002/phar.2335","DOIUrl":"https://doi.org/10.1002/phar.2335","url":null,"abstract":"Bivalirudin, a direct thrombin inhibitor, is a treatment option for the management of heparin‐induced thrombocytopenia (HIT) and other coagulation disorders. To date, no published studies have identified patients at risk for or the consequence of subtherapeutic bivalirudin therapy.","PeriodicalId":19812,"journal":{"name":"Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80202425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Blanco Dorado, O. Maroñas, Ana Latorre-Pellicer, Teresa Rodríguez Jato, Ana López-Vizcaíno, Áurea María Gómez Márquez, B. Bardán García, Dolores Belles Medall, G. Barbeito Castiñeiras, M. L. Pérez Del Molino Bernal, M. Campos‐Toimil, F. O. Otero Espinar, Andrés Blanco Hortas, G. Durán Piñeiro, I. Zarra Ferro, Á. Carracedo, M. Lamas, A. Fernández-Ferreiro
Voriconazole, a first‐line agent for the treatment of invasive fungal infections, is mainly metabolized by cytochrome P450 (CYP) 2C19. A significant portion of patients fail to achieve therapeutic voriconazole trough concentrations, with a consequently increased risk of therapeutic failure.
{"title":"Impact of CYP2C19 Genotype and Drug Interactions on Voriconazole Plasma Concentrations: A Spain Pharmacogenetic‐Pharmacokinetic Prospective Multicenter Study","authors":"S. Blanco Dorado, O. Maroñas, Ana Latorre-Pellicer, Teresa Rodríguez Jato, Ana López-Vizcaíno, Áurea María Gómez Márquez, B. Bardán García, Dolores Belles Medall, G. Barbeito Castiñeiras, M. L. Pérez Del Molino Bernal, M. Campos‐Toimil, F. O. Otero Espinar, Andrés Blanco Hortas, G. Durán Piñeiro, I. Zarra Ferro, Á. Carracedo, M. Lamas, A. Fernández-Ferreiro","doi":"10.1002/phar.2351","DOIUrl":"https://doi.org/10.1002/phar.2351","url":null,"abstract":"Voriconazole, a first‐line agent for the treatment of invasive fungal infections, is mainly metabolized by cytochrome P450 (CYP) 2C19. A significant portion of patients fail to achieve therapeutic voriconazole trough concentrations, with a consequently increased risk of therapeutic failure.","PeriodicalId":19812,"journal":{"name":"Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82951278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Access to naloxone is a priority for reducing opioid deaths. Although community members who complete naloxone training are able to administer nasal naloxone successfully and rapidly, little is known about the ability of community members to administer naloxone without training. The objective of this study was to assess the ability of untrained individuals to administer naloxone successfully in a simulated opioid overdose setting.
{"title":"Naloxone Administration by Untrained Community Members","authors":"W. Eggleston, V. Calleo, Martin Kim, S. Wojcik","doi":"10.1002/phar.2352","DOIUrl":"https://doi.org/10.1002/phar.2352","url":null,"abstract":"Access to naloxone is a priority for reducing opioid deaths. Although community members who complete naloxone training are able to administer nasal naloxone successfully and rapidly, little is known about the ability of community members to administer naloxone without training. The objective of this study was to assess the ability of untrained individuals to administer naloxone successfully in a simulated opioid overdose setting.","PeriodicalId":19812,"journal":{"name":"Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77366033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Perreault, S. de Denus, B. White-Guay, R. Cote, M. Schnitzer, M. Dubé, M. Dorais, J. Tardif
Data on oral anticoagulant (OAC) uptake and pattern of use are limited. Real‐life data in patients with atrial fibrillation (AF) are important for understanding patient exposure. A cohort study of new OAC users was built to assess trends of drug use from 2011 to 2017, persistence rate, switching rate, adherence level, and predictors of adherence.
{"title":"Oral Anticoagulant Prescription Trends, Profile Use, and Determinants of Adherence in Patients with Atrial Fibrillation","authors":"S. Perreault, S. de Denus, B. White-Guay, R. Cote, M. Schnitzer, M. Dubé, M. Dorais, J. Tardif","doi":"10.1002/phar.2350","DOIUrl":"https://doi.org/10.1002/phar.2350","url":null,"abstract":"Data on oral anticoagulant (OAC) uptake and pattern of use are limited. Real‐life data in patients with atrial fibrillation (AF) are important for understanding patient exposure. A cohort study of new OAC users was built to assess trends of drug use from 2011 to 2017, persistence rate, switching rate, adherence level, and predictors of adherence.","PeriodicalId":19812,"journal":{"name":"Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75886954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yanjun Zhao, T. Seelhammer, E. Barreto, John W. Wilson
Drug pharmacokinetics may be significantly altered in patients receiving extracorporeal membrane oxygenation (ECMO). Ensuring the optimized effective dosing of antimicrobials on ECMO remains a challenge. To date, limited data are available regarding the optimal use of amphotericin and triazoles during ECMO. We report a case of altered pharmacokinetics, insufficient liposomal amphotericin B and isavuconazole levels, and the need for escalated doses during ECMO in a patient with severe acute respiratory distress syndrome secondary to pulmonary blastomycosis. A 2‐fold increase in the standard total daily dose of both drugs was necessary to overcome low serum concentrations thought to be secondary to drug loss from ECMO circuit sequestration. These findings have important implications for optimizing antimicrobial therapy in patients receiving ECMO to maximize therapeutic efficacy. The use of therapeutic drug monitoring for patients receiving antimicrobial therapy with concurrent ECMO may facilitate appropriate drug dosing to achieve adequate serum concentrations and optimize favorable patient outcomes. Further studies exploring antimicrobial pharmacokinetics during ECMO are needed to inform dosing recommendations in critically ill patients.
{"title":"Altered Pharmacokinetics and Dosing of Liposomal Amphotericin B and Isavuconazole during Extracorporeal Membrane Oxygenation","authors":"Yanjun Zhao, T. Seelhammer, E. Barreto, John W. Wilson","doi":"10.1002/phar.2348","DOIUrl":"https://doi.org/10.1002/phar.2348","url":null,"abstract":"Drug pharmacokinetics may be significantly altered in patients receiving extracorporeal membrane oxygenation (ECMO). Ensuring the optimized effective dosing of antimicrobials on ECMO remains a challenge. To date, limited data are available regarding the optimal use of amphotericin and triazoles during ECMO. We report a case of altered pharmacokinetics, insufficient liposomal amphotericin B and isavuconazole levels, and the need for escalated doses during ECMO in a patient with severe acute respiratory distress syndrome secondary to pulmonary blastomycosis. A 2‐fold increase in the standard total daily dose of both drugs was necessary to overcome low serum concentrations thought to be secondary to drug loss from ECMO circuit sequestration. These findings have important implications for optimizing antimicrobial therapy in patients receiving ECMO to maximize therapeutic efficacy. The use of therapeutic drug monitoring for patients receiving antimicrobial therapy with concurrent ECMO may facilitate appropriate drug dosing to achieve adequate serum concentrations and optimize favorable patient outcomes. Further studies exploring antimicrobial pharmacokinetics during ECMO are needed to inform dosing recommendations in critically ill patients.","PeriodicalId":19812,"journal":{"name":"Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88719130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J. Podichetty, B. Brinda, R. Nelson, Alissa H. Karr, N. Prasad, S. Quinney, Susanna Foxworthy Scott, P. Kiel
Basiliximab is an immunosuppressive monoclonal antibody used for rejection prevention following solid organ transplantation; the pharmacokinetics (PK) of basiliximab in this setting are known. Basiliximab may also be used for prophylaxis and treatment of graft‐versus‐host disease (GVHD) in patients undergoing allogeneic hematopoietic cell transplantation (HCT); however, the PK of basiliximab in this setting are not known. Clinical transplant providers expect variation in the volume of distribution and clearance after nonmyeloablative allogeneic transplantation (NMAT) compared with solid organ transplantation. Blood loss, organ site–specific antibody accumulation, and differences in blood product use during the two transplantation approaches may generate differences in basiliximab PK. Therefore, the objective of this study was to describe the PK of basiliximab after its addition to a minimally intense NMAT regimen, in conjunction with cyclosporine, for GVHD prophylaxis in patients with hematologic malignancies.
{"title":"Pharmacokinetics of Basiliximab for the Prevention of Graft‐versus‐Host Disease in Patients Undergoing Hematopoietic Cell Transplantation with Minimal‐Intensity Cyclophosphamide and Fludarabine","authors":"J. Podichetty, B. Brinda, R. Nelson, Alissa H. Karr, N. Prasad, S. Quinney, Susanna Foxworthy Scott, P. Kiel","doi":"10.1002/phar.2347","DOIUrl":"https://doi.org/10.1002/phar.2347","url":null,"abstract":"Basiliximab is an immunosuppressive monoclonal antibody used for rejection prevention following solid organ transplantation; the pharmacokinetics (PK) of basiliximab in this setting are known. Basiliximab may also be used for prophylaxis and treatment of graft‐versus‐host disease (GVHD) in patients undergoing allogeneic hematopoietic cell transplantation (HCT); however, the PK of basiliximab in this setting are not known. Clinical transplant providers expect variation in the volume of distribution and clearance after nonmyeloablative allogeneic transplantation (NMAT) compared with solid organ transplantation. Blood loss, organ site–specific antibody accumulation, and differences in blood product use during the two transplantation approaches may generate differences in basiliximab PK. Therefore, the objective of this study was to describe the PK of basiliximab after its addition to a minimally intense NMAT regimen, in conjunction with cyclosporine, for GVHD prophylaxis in patients with hematologic malignancies.","PeriodicalId":19812,"journal":{"name":"Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74824500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The pathogenic mechanism of antituberculous drug‐induced liver injury (ATDILI) is associated with antioxidant enzymes. The objective of the present study was to investigate the associations of ATDILI susceptibility with genetic polymorphisms of antioxidant enzyme genes including nitric oxide synthase 2 (NOS2), thioredoxin reductase 1 (TXNRD1), superoxide dismutase 2 (SOD2), BTB domain and CNC homolog 1 (BACH1), and MAF bZIP transcription factor K (MAFK).
{"title":"Genetic Polymorphisms in Antioxidant Enzymes Modulate the Susceptibility of Idiosyncratic Antituberculous Drug‐Induced Liver Injury and Treatment Outcomes in Patients with Tuberculosis","authors":"Q. Sun, W. Sha, Haipeng Liu, Peng Wang, Zhi-bin Liu, Wen Sun, He-ping Xiao","doi":"10.1002/phar.2349","DOIUrl":"https://doi.org/10.1002/phar.2349","url":null,"abstract":"The pathogenic mechanism of antituberculous drug‐induced liver injury (ATDILI) is associated with antioxidant enzymes. The objective of the present study was to investigate the associations of ATDILI susceptibility with genetic polymorphisms of antioxidant enzyme genes including nitric oxide synthase 2 (NOS2), thioredoxin reductase 1 (TXNRD1), superoxide dismutase 2 (SOD2), BTB domain and CNC homolog 1 (BACH1), and MAF bZIP transcription factor K (MAFK).","PeriodicalId":19812,"journal":{"name":"Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76008305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jason Yerke, Gretchen L. Sacha, R. Scheraga, D. Culver, Susamma Abraham, Heather Torbic, S. Lam, Mahmoud A. Ammar, M. Olman, S. Bauer
Positive hemodynamic response to vasopressin after 6 hours of infusion was independently associated with lower mortality in a previous retrospective study of patients with septic shock. However, factors previously associated with higher plasma vasopressin concentration were not associated with response, and the relationship between plasma vasopressin concentration and hemodynamic response has not been evaluated.
{"title":"Vasopressin Plasma Concentrations Are Not Associated with Hemodynamic Response to Exogenous Vasopressin for Septic Shock","authors":"Jason Yerke, Gretchen L. Sacha, R. Scheraga, D. Culver, Susamma Abraham, Heather Torbic, S. Lam, Mahmoud A. Ammar, M. Olman, S. Bauer","doi":"10.1002/phar.2346","DOIUrl":"https://doi.org/10.1002/phar.2346","url":null,"abstract":"Positive hemodynamic response to vasopressin after 6 hours of infusion was independently associated with lower mortality in a previous retrospective study of patients with septic shock. However, factors previously associated with higher plasma vasopressin concentration were not associated with response, and the relationship between plasma vasopressin concentration and hemodynamic response has not been evaluated.","PeriodicalId":19812,"journal":{"name":"Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83232332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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