Clinical Pharmacology : Advances and Applications最新文献

{"title":"Metformin as a Potential Adjuvant Antimicrobial Agent Against Multidrug Resistant Bacteria.","authors":"Majed M Masadeh,&nbsp;Karem H Alzoubi,&nbsp;Majd M Masadeh,&nbsp;Zainah O Aburashed","doi":"10.2147/CPAA.S297903","DOIUrl":"https://doi.org/10.2147/CPAA.S297903","url":null,"abstract":"<p><strong>Introduction: </strong>The continuous increase in the incidence of bacterial resistance to existing antibiotics represents a worldwide health burden. A surrogate strategy to combat such crisis is to find compounds that restore the antimicrobial activity of the already existing antibiotics against multidrug resistant bacteria. Metformin is a commonly used antidiabetic medication. It has proven benefits in other diseases including cancer, aging-related and infectious diseases. In this study, the potential effect of metformin as an adjuvant therapy to antibiotics was investigated.</p><p><strong>Methods: </strong>Two multidrug resistant bacterial strains were used; methicillin-resistant <i>Staphylococcus aureus</i> (MRSA; ATCC 33,591) and multidrug resistant <i>Pseudomonas aeruginosa</i> (ATCC BAA-2114). To assess its efficacy, metformin was combined with several antibiotics: levofloxacin, chloramphenicol, rifampicin, ampicillin, and doxycycline. The antibacterial effect of metformin was tested using the micro broth dilution method. The minimum inhibitory concentration (MIC) was also measured. Cytotoxicity studies were also performed on mammalian cells to assess its safety.</p><p><strong>Results: </strong>Metformin exhibited an antibacterial effect when combined with the antibiotics on the two tested strains. It also showed low toxicity on the mammalian cells. Moreover, synergetic studies showed that metformin enhanced the effect of the combined antibiotics, as these combinations provide either a synergistic or additive effect with significant reduction in the MIC.</p><p><strong>Conclusion: </strong>Metformin exerts an adjuvant antibacterial effect; thus, it could be a possible candidate as an adjuvant therapy to reduce antimicrobial resistance.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":" ","pages":"83-90"},"PeriodicalIF":2.0,"publicationDate":"2021-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/54/10/cpaa-13-83.PMC8123943.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38996517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Population Pharmacokinetics of CC-122.","authors":"Yiming Cheng,&nbsp;Jian Chen,&nbsp;Michael Pourdehnad,&nbsp;Simon Zhou,&nbsp;Yan Li","doi":"10.2147/CPAA.S310604","DOIUrl":"https://doi.org/10.2147/CPAA.S310604","url":null,"abstract":"<p><strong>Background: </strong>CC-122 is a cereblon-modulating agent that exerts direct cell-autonomous activity against malignant B cells and immunomodulatory effects. Herein, a population pharmacokinetic (popPK) model of CC-122 was developed and the influence of demographic and disease-related covariates on population pharmacokinetic parameters was assessed based on data from three clinical studies of CC-122 (dose range, 0.5-15 mg) in healthy subjects and cancer patients.</p><p><strong>Methods: </strong>Nonlinear mixed effects modeling was employed in developing a population pharmacokinetic model of CC-122 based on 298 patients from 3 clinical studies.</p><p><strong>Results: </strong>The PK of CC-122 was adequately described with a two-compartment model with first-order absorption and elimination. Tumor types were found to be significantly correlated with apparent clearance (CL/F) and apparent volume of distribution of the central compartment. Creatinine clearance was identified as a statistically significant covariate of CL/F. Sex and body weight were statistically but not clinically relevant on V2/F.</p><p><strong>Conclusion: </strong>In conclusion, the two-compartment model built can be used to adequately describe the time course of the population pharmacokinetics of CC-122 and should serve as the basis for dose adjustment decision-making of CC-122.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":" ","pages":"61-71"},"PeriodicalIF":2.0,"publicationDate":"2021-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/59/02/cpaa-13-61.PMC8093142.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38958048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of Generic Atorvastatin in a Real-World Setting.","authors":"Panisa Manasirisuk,&nbsp;Nanthaphan Chainirun,&nbsp;Somsak Tiamkao,&nbsp;Sunee Lertsinudom,&nbsp;Kutcharin Phunikhom,&nbsp;Bundit Sawunyavisuth,&nbsp;Kittisak Sawanyawisuth","doi":"10.2147/CPAA.S285750","DOIUrl":"https://doi.org/10.2147/CPAA.S285750","url":null,"abstract":"<p><strong>Background: </strong>The ability of statins to reduce LDL-c plays an important role in both primary and secondary prevention of atherosclerotic cardiovascular diseases. Such treatment can often be costly, but using generic atorvastatin may reduce cost by up to US$2635. In addition, a previous 8-week study found that it exhibited comparable efficacy to the brand-name medication. This study aimed to evaluate the efficacy of generic atorvastatin over a longer period of six months in a real-world setting.</p><p><strong>Methods: </strong>This was a retrospective cohort study in adult patients who had received brand-name atorvastatin for at least three months and then had switched to generic atorvastatin for at least six months. Lipid and safety profiles were evaluated at six months after switching. Adjusted analyses for age, sex, co-morbid disease, dosage, and indications for statin therapy were also performed.</p><p><strong>Results: </strong>During the study period, there were 488 patients who met the study criteria. The mean (SD) age of the patients was 60.97 (12.26) years, and 48.36% were male (236 patients). At six months, average total cholesterol, HDL-c, and LDL-c were all lower, from 174.43 to 166.15 mg/dL, from 51.64 to 49.51 mg/dL, and from 110.08 to 100.78 mg/dL (p < 0.001), respectively. There were no significant differences in terms of any other laboratory test results. LDL-c exhibited the highest significant reduction at 9.30 mg/dL. Stratified analyses by age, sex, co-morbid disease, dose, and indications for statin therapy revealed similar decreases in HDL-c and LDL-c as in the study population as a whole.</p><p><strong>Conclusion: </strong>Generic atorvastatin resulted in significantly lower LDL-c than name-brand atorvastatin but less of an increase in HDL-c.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":" ","pages":"45-51"},"PeriodicalIF":2.0,"publicationDate":"2021-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/23/f4/cpaa-13-45.PMC7943322.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25466572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Parkinson's Disease: Carbidopa, Nausea, and Dyskinesia [Retraction].","authors":"","doi":"10.2147/CPAA.S308259","DOIUrl":"https://doi.org/10.2147/CPAA.S308259","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.2147/CPAA.S72234.].</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":" ","pages":"43"},"PeriodicalIF":2.0,"publicationDate":"2021-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/85/71/cpaa-13-43.PMC7937382.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25466910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Parkinson's Disease Death Rate: Carbidopa and Vitamin B6 [Retraction].","authors":"","doi":"10.2147/CPAA.S308256","DOIUrl":"https://doi.org/10.2147/CPAA.S308256","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.2147/CPAA.S70707.].</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":" ","pages":"41"},"PeriodicalIF":2.0,"publicationDate":"2021-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9b/a1/cpaa-13-41.PMC7937393.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25466909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Administration of Supplemental L-Tyrosine with Phenelzine: a Clinical Literature Review [Retraction].","authors":"","doi":"10.2147/CPAA.S308255","DOIUrl":"https://doi.org/10.2147/CPAA.S308255","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.2147/CPAA.S67271.].</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":" ","pages":"39"},"PeriodicalIF":2.0,"publicationDate":"2021-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/43/5e/cpaa-13-39.PMC7937379.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25466908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Successful Control of Hypoglycemia with Pasireotide LAR in a Patient with Inappropriate Insulin Secretion.","authors":"Alexia Rouland,&nbsp;Benjamin Bouillet,&nbsp;Pauline Legris,&nbsp;Isabelle Simoneau,&nbsp;Jean-Michel Petit,&nbsp;Bruno Vergès","doi":"10.2147/CPAA.S278978","DOIUrl":"https://doi.org/10.2147/CPAA.S278978","url":null,"abstract":"<p><strong>Introduction: </strong>Inappropriate insulin secretion could be due to several diseases. Nesidioblastosis is characterized by diffuse hyperplasia of pancreatic beta cells, causing organic hypoglycemia. No pancreatic lesions are found on the imaging of patients with this condition. Diazoxide is used as a first-line treatment but can be poorly tolerated because of its side effects, and therapeutic failure is possible. Somatostatin analogues have limited efficacy because of their poor affinity to somatostatin (SST) receptors. Pasireotide is a somatostatin analogue with a much higher affinity to SST receptors, especially SST5, and it could thus be more efficient for treating nesidioblastosis-related hypoglycemia.</p><p><strong>Observation: </strong>A 56 years-old diabetic woman had symptoms of hypoglycemia, persistent after treatment's withdrawal. A fasting test authentify an organic hypoglycemia, at 34mg/dL, a plasma insulin level at 6mUI/L above the 5 mU/L threshold, a C-peptide level at 1.9 ng/mL above the threshold of 0.6, and an insulin/C-peptide ratio 0.066, below the threshold of 1. No lesions were found on CT-scan or endoscopic ultrasound. Somatostatin receptor scintigraphy was also negative. Diazoxide and octreotide failed to improve the recurrence of hypoglycemia episodes. With pasireotide LAR, hypoglycemia disappeared and glycemia increased. Hyperglycemia was controlled with sitagliptin. The patient has now been treated with pasireotide LAR for two years, with no more episode of hypoglycemia until now.</p><p><strong>Discussion: </strong>We present the first case of nesidioblastosis treatment with pasireotide LAR, with success. Patients diagnosed with nesidioblastosis and diazoxide-resistant hypoglycemia, or who experience difficulties with other treatments, could use pasireotide LAR in conjunction with glycemia monitoring, particularly if they are diabetic.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":" ","pages":"33-37"},"PeriodicalIF":2.0,"publicationDate":"2021-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/53/cd/cpaa-13-33.PMC7872904.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25359851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics and Toxicities of Oral Docetaxel Formulations Co-Administered with Ritonavir in Phase I Trials.","authors":"Marit Vermunt,&nbsp;Serena Marchetti,&nbsp;Jos Beijnen","doi":"10.2147/CPAA.S292746","DOIUrl":"https://doi.org/10.2147/CPAA.S292746","url":null,"abstract":"<p><strong>Introduction: </strong>Docetaxel is widely used as intravenous (IV) chemotherapy. Oral docetaxel is co-administered with the cytochrome P450 3A4 and P-glycoprotein inhibitor ritonavir to increase oral bioavailability. This research explores the relationship between the pharmacokinetics (PK) and toxicity of this novel oral chemotherapy.</p><p><strong>Methods: </strong>The patients in two phase I trials were treated with different oral docetaxel formulations in combination with ritonavir in different dose levels, ranging from 20 to 80 mg docetaxel with 100 to 200 mg ritonavir a day. The patients were categorized based on the absence or occurrence of severe treatment-related toxicity (grade ≥3 or any grade leading to treatment alterations). The docetaxel area under the plasma concentration-time curve (AUC) and maximum plasma concentration (C_max) were associated with toxicity.</p><p><strong>Results: </strong>Thirty-four out of 138 patients experienced severe toxicity, most frequently observed as mucositis, fatigue, diarrhea, nausea and vomiting. The severe toxicity group had a significantly higher docetaxel AUC (2231 ± 1405 vs 1011 ± 830 ng/mL*h, p<0.0001) and C_max (218 ± 178 vs 119 ± 77 ng/mL, p<0.0001) as compared to the patients without severe toxicity. When extrapolated from IV PK data, the patients without severe toxicity had a similar cumulative docetaxel AUC as with standard 3-weekly IV docetaxel, while the C_max was up to 10-fold lower with oral docetaxel and ritonavir.</p><p><strong>Conclusion: </strong>Severe toxicity was observed in 25% of the patients treated with oral docetaxel and ritonavir. This toxicity seems related to the PK, as the docetaxel AUC_0-inf and C_max were up to twofold higher in the severe toxicity group as compared to the non-severe toxicity group. Future randomized trials will provide a further evaluation of the toxicity and efficacy of the new weekly oral docetaxel and ritonavir regimen in comparison to standard IV docetaxel.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":" ","pages":"21-32"},"PeriodicalIF":2.0,"publicationDate":"2021-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e7/d2/cpaa-13-21.PMC7850405.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25328910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Wound Healing Effect of <i>Acokanthera schimperi</i> Schweinf (Apocynaceae) Methanol Leaf Extract Ointment in Mice and Its in-vitro Antioxidant Activity.","authors":"Belete Kassa Alemu,&nbsp;Desye Misganaw,&nbsp;Getnet Mengistu","doi":"10.2147/CPAA.S288394","DOIUrl":"https://doi.org/10.2147/CPAA.S288394","url":null,"abstract":"<p><strong>Background: </strong><i>Acokanthera schimperi</i> is traditionally used for the treatment of wounds and various bacterial infections. Due to the ongoing escalation of antimicrobial resistance, there is an increasing demand for the appropriate wound care and hence, the present study was initiated to investigate the wound healing effects of the leaf extract ointments of <i>A. schimperi</i> in mice and its in-vitro antioxidant activity.</p><p><strong>Methods: </strong>The crude extract was prepared as 5% and 10% w/w ointments for topical use in mice. Wound contraction and epithelialization period were determined in excision and infected models, whereas tensile strength was determined in an incision model. Besides, its antioxidant activity was evaluated using the DPPH method.</p><p><strong>Results: </strong>In this study, the 10% w/w extract ointment did not cause toxicity at the 2000 mg/kg limit dose. In the excision model, the 10% w/w ointment exhibited a significant wound contraction effect starting from day 6 to 14 with a complete epithelization shown on day 13. Besides, the 5%w/w ointment showed a significant wound contraction effect starting from day 6 onwards, and a significant decrease in the epithelization period observed on day 16. Conversely, both the 10% w/w and 5% w/w ointments showed significant wound contraction effects starting from day 4 and onwards in the infected model. However, a complete epithelization period was observed on days 14 and 18 in the 10%w/w and 5% w/w/extract ointment treated groups, respectively. In the incision model, the 10% (w/w) and 5% (w/w) extract ointments showed a significant increase in tensile strength by 36.80 and 32.23%, respectively. Moreover, the antioxidant activity of the extract was concentration-dependent with an IC50 value of 5.49± 0.38 µg/µL.</p><p><strong>Conclusion: </strong>The potential wound healing effects of this plant may provide a candidate source in the discovery of new drugs for the treatment of wounds.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"12 ","pages":"213-222"},"PeriodicalIF":2.0,"publicationDate":"2020-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/06/c6/cpaa-12-213.PMC7780988.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38791306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Up-to-Date Overview of Therapeutic Agents for the Treatment of COVID-19 Disease.","authors":"Tafere Mulaw Belete","doi":"10.2147/CPAA.S284809","DOIUrl":"10.2147/CPAA.S284809","url":null,"abstract":"<p><p>Acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has a great potential to overwhelm the world healthcare systems that may lead to high morbidity and mortality. It also affects world economic development in the future. Currently, no proven effective drugs or vaccines are available for the management of COVID-19 disease. The pace of normal drug development progression is unacceptable in the context of the current pandemic. Therefore, repurposing the existing drugs that were used for the treatment of malaria, Ebola, and influenza helps rapid drug development for COVID-19. Currently, several repurposing candidate drugs are in a clinical trial including, chloroquine monoclonal antibodies, convalescent plasma, interferon, and antiviral therapies. Antiviral drugs like arbidol, remdesiv and favirnavir are the most promising due to the similarities of the viruses regarding viral entry, fusion, uncoating, and replication. This review article provides an overview of the potential therapeutic agent, which displayed better clinical treatment outcomes. Moreover, with further understanding of the SARS-CoV-2 virus, new drugs targeting specific SARS-CoV-2 viral components arise, and investigations on these novels anti-SARSCoV- 2 agents are also reviewed.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"12 ","pages":"203-212"},"PeriodicalIF":2.0,"publicationDate":"2020-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a3/3f/cpaa-12-203.PMC7753885.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38750941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}