Clinical Pharmacology : Advances and Applications最新文献

{"title":"Pharmacokinetic equivalence study of nonsteroidal anti-inflammatory drug etoricoxib.","authors":"Raymond R Tjandrawinata, Arini Setiawati, Dwi Nofiarny, Liana W Susanto, Effi Setiawati","doi":"10.2147/CPAA.S161024","DOIUrl":"10.2147/CPAA.S161024","url":null,"abstract":"<p><strong>Purpose: </strong>The current study aimed to evaluate whether a generic product of etoricoxib 120 mg film-coated tablet (the test drug) was bioequivalent to the reference product (Arcoxia® film-coated tablet 120 mg).</p><p><strong>Methods: </strong>This was a randomized, open-label, two-sequence, crossover study under fasting condition, with a 14-day washout period, involving 26 healthy adult male and female subjects. Blood samples were taken and analyzed for plasma concentrations of etoricoxib (Chemical Abstracts Service [CAS] 202409-33-4) using a high-pressure liquid chromatography-ultraviolet detector (HPLC-UV) system capable of measuring etoricoxib concentrations ranging from 5.00 to 5002.90 ng/mL, with the lowest limit of quantitation of 5.00 ng/mL. A noncompartmental method was used to determine the pharmacokinetic parameters of a single-dose administration of the drug, including the area under plasma concentration-time curve from time zero to the time of last observed concentration (AUC_0-<i>_t</i> ), the area under plasma concentration-time curve from time zero to infinity (AUC_0-∞), the maximum plasma concentration (<i>C</i>_max), the time to reach the maximum plasma concentration (<i>t</i>_max), and the terminal half-life (<i>t</i>_½).</p><p><strong>Results: </strong>After a single-dose administration of etoricoxib 120 mg film-coated tablet, the mean (SD) values for the AUC_0-72h and <i>C</i>_max of the test drug were 45913.42 (13142.19) ng·h/mL and 3155.93 (752.81) ng/mL, respectively; the values for the reference drug were 44577.20 (13541.85) ng·h/mL and 2915.13 (772.81) ng/mL, respectively. The geometric mean ratios (90% CIs) of the test drug/reference drug were 103.40% (98.70%-108.32%) for AUC_0-72h and 109.26% (100.18%-119.18%) for <i>C</i>_max. No clinically significant differences in <i>t</i>_max and <i>t</i>_½values were found between the test drug and the reference drug. No adverse events were experienced by the subjects during this study.</p><p><strong>Conclusion: </strong>The present study demonstrated that the evaluated generic etoricoxib 120 mg film-coated tablets were bioequivalent to the reference drug.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"10 ","pages":"43-51"},"PeriodicalIF":2.0,"publicationDate":"2018-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/65/22/cpaa-10-043.PMC5896653.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36022483","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":"Safinamide: an add-on treatment for managing Parkinson's disease.","authors":"Thomas Müller","doi":"10.2147/CPAA.S137740","DOIUrl":"10.2147/CPAA.S137740","url":null,"abstract":"<p><p>Heterogeneous expression of neurotransmitter deficits results from onset and progression of Parkinson's disease. Intervals, characterized by reappearance of motor and associated certain nonmotor symptoms, determine the end of good tolerability and efficacy of oral levodopa therapy. These \"OFF\" states result from levodopa pharmacokinetics and disease progression-related deterioration of the central buffering capacity for fluctuations of dopamine levels. This review discusses safinamide as an add-on therapeutic agent in orally levodopa-treated patients with \"OFF\" phenomena. Safinamide provided beneficial effects on \"OFF\" symptoms in pivotal trials with doses of 50 or 100 mg once daily. Safinamide reversibly inhibits mono-amine oxidase B and declines abnormal glutamate release by modulation of potassium- and sodium ion channels. An ideal candidate for combination with safinamide is opicapone. This inhibitor of peripheral catechol-O-methyltransferase supports continuous brain delivery of levodopa and, thus, the continuous dopaminergic stimulation concept. Both compounds with their once-daily application and good tolerability may complement each other by reduction of necessary oral levodopa intakes and \"OFF\" times. Thus, a promising, future option will be combination of safinamide and opicapone in one formulation. It will reduce adherence issues and may complement levodopa treatment. It will probably cause less nausea and edema than a dopamine agonist/levodopa regimen.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"10 ","pages":"31-41"},"PeriodicalIF":2.0,"publicationDate":"2018-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S137740","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36022062","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":"Pramlintide, an antidiabetic, is antineoplastic in colorectal cancer and synergizes with conventional chemotherapy.","authors":"Maha S Al-Keilani,&nbsp;Dua H Alsmadi,&nbsp;Ruba S Darweesh,&nbsp;Karem H Alzoubi","doi":"10.2147/CPAA.S153780","DOIUrl":"https://doi.org/10.2147/CPAA.S153780","url":null,"abstract":"<p><strong>Background: </strong>Approximately 90% of patients with metastatic colorectal cancer fail therapy mainly due to resistance. Taking advantage of currently approved agents for treatment of disease conditions other than cancer for the identification of new adjuvant anticancer therapies is highly encouraged. Pramlintide is a parenteral antidiabetic agent that is currently approved for treatment of types 1 and 2 diabetes mellitus.</p><p><strong>Objectives: </strong>To address the antineoplastic potential of pramlintide in colorectal cancer and to evaluate the ability of pramlintide to enhance the cytotoxicity of 5-fluorouracil, oxaliplatin, and irinotecan against colorectal cancer cell lines expressing wild-type and mutant p53.</p><p><strong>Materials and methods: </strong>The antiproliferative effect of pramlintide alone or in combination with 5-fluorouracil, oxaliplatin, or irinotecan in HCT-116 and HT-29 colorectal cancer cell lines was investigated using MTT cell proliferation assay. IC50 values were calculated using Compusyn software 1.0. Synergy values (R) were calculated using the ratio of IC50 of each primary drug alone divided by combination IC50s. For each two pairs of experiments, Student's <i>t</i>-test was used for analysis. For combination studies, one-way analysis of variance and Tukey post hoc testing was performed using R 3.3.2 software. A <i>p</i>-value of <0.05 was considered significant.</p><p><strong>Results: </strong>Pramlintide inhibited the growth of HCT-116 and HT-29 in a dose-dependent manner, with higher efficacy against the latter (IC50s; 48.67 and 9.10 μg/mL, respectively; <i>p</i>-value =0.013). Moreover, the addition of 5, 10, and 20 μg/mL of pramlintide to HCT-116 and HT-29 with 5-fluorouracil, oxaliplatin, or irinotecan induced the antiproliferative effect synergistically (<i>R</i>>1.6, <i>p</i>-value <0.05).</p><p><strong>Conclusion: </strong>Pramlintide enhances the cytotoxicity of conventional chemotherapy against colorectal cancer cell lines harboring wild-type or mutant p53. Thus, pramlintide is a promising potential adjuvant chemotherapy in colorectal cancer.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"10 ","pages":"23-29"},"PeriodicalIF":2.0,"publicationDate":"2018-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S153780","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35924725","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":"A review of the pharmacology and clinical efficacy of brivaracetam.","authors":"Pavel Klein, Anyzeila Diaz, Teresa Gasalla, John Whitesides","doi":"10.2147/CPAA.S114072","DOIUrl":"10.2147/CPAA.S114072","url":null,"abstract":"<p><p>Brivaracetam (BRV; Briviact) is a new antiepileptic drug (AED) approved for adjunctive treatment of focal (partial-onset) seizures in adults. BRV is a selective, high-affinity ligand for synaptic vesicle 2A (SV2A) with 15- to 30-fold higher affinity than levetiracetam, the first AED acting on SV2A. It has high lipid solubility and rapid brain penetration, with engagement of the target molecule, SV2A, within minutes of administration. BRV has potent broad-spectrum antiepileptic activity in animal models. Phase I studies indicated BRV was well tolerated and showed a favorable pharmacokinetic profile over a wide dose range following single (10-1,000 mg) and multiple (200-800 mg/day) oral dosing. Three pivotal Phase III studies have demonstrated promising efficacy and a good safety and tolerability profile across doses of 50-200 mg/day in the adjunctive treatment of refractory focal seizures. Long-term data indicate that the response to BRV is sustained, with good tolerability and retention rate. BRV is highly effective in patients experiencing secondarily generalized tonic-clonic seizures. Safety data to date suggest a favorable psychiatric adverse effect profile in controlled studies, although limited postmarketing data are available. BRV is easy to use, with no titration and little drug-drug interaction. It can be initiated at target dose with no titration. Efficacy is seen on day 1 of oral use in a significant percentage of patients. Intravenous administration in a 2-minute bolus and 15-minute infusion is well tolerated. Here, we review the pharmacology, pharmacokinetics, and clinical data of BRV.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"10 ","pages":"1-22"},"PeriodicalIF":3.1,"publicationDate":"2018-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6d/51/cpaa-10-001.PMC5783144.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35797828","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":"CRTH2 antagonists in asthma: current perspectives.","authors":"Dave Singh,&nbsp;Arjun Ravi,&nbsp;Thomas Southworth","doi":"10.2147/CPAA.S119295","DOIUrl":"https://doi.org/10.2147/CPAA.S119295","url":null,"abstract":"<p><p>Chemoattractant receptor-homologous molecule expressed on T_H2 cells (CRTH2) binds to prostaglandin D₂. CRTH2 is expressed on various cell types including eosinophils, mast cells, and basophils. CRTH2 and prostaglandin D₂ are involved in allergic inflammation and eosinophil activation. Orally administered CRTH2 antagonists are in clinical development for the treatment of asthma. The biology and clinical trial data indicate that CRTH2 antagonists should be targeted toward eosinophilic asthma. This article reviews the clinical evidence for CRTH2 involvement in asthma pathophysiology and clinical trials of CRTH2 antagonists in asthma. CRTH2 antagonists could provide a practical alternative to biological treatments for patients with severe asthma. Future perspectives for this class of drug are considered, including the selection of the subgroup of patients most likely to show a meaningful treatment response.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"9 ","pages":"165-173"},"PeriodicalIF":2.0,"publicationDate":"2017-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S119295","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35687177","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":"Olaratumab: a platelet-derived growth factor receptor-α-blocking antibody for the treatment of soft tissue sarcoma.","authors":"Alexandra Pender,&nbsp;Robin L Jones","doi":"10.2147/CPAA.S130178","DOIUrl":"https://doi.org/10.2147/CPAA.S130178","url":null,"abstract":"<p><p>The outcome of patients with unresectable or metastatic soft tissue sarcoma (STS) remains poor with few treatment options. A number of randomized trials in the first-line setting have shown no difference in overall survival between combination anthracycline schedules and single-agent doxorubicin. A Phase Ib/randomized Phase II trial of doxorubicin with or without the platelet-derived growth factor receptor-α (PDGFRα)-blocking antibody, olaratumab, demonstrated a significant difference in median overall survival in favor of the olaratumab arm. The results of this trial led to the approval of olaratumab in combination with doxorubicin in adult anthracycline-naïve unresectable STS. In this review, we discuss the potential role of PDGFRα signaling, early clinical data with olaratumab in sarcomas, the Phase Ib/II trial and ongoing trials with olaratumab in sarcomas.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"9 ","pages":"159-164"},"PeriodicalIF":2.0,"publicationDate":"2017-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S130178","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35681843","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":"Role of afatinib in the treatment of advanced lung squamous cell carcinoma.","authors":"Tiziana Vavalà","doi":"10.2147/CPAA.S112715","DOIUrl":"https://doi.org/10.2147/CPAA.S112715","url":null,"abstract":"<p><p>Lung cancer treatment has considerably changed over the last few years: the identification of druggable oncogenic alterations and innovative immunotherapic approaches granted lung cancer patients the possibility of more efficient and less toxic therapeutic options than chemotherapy. Nowadays, lung squamous cell carcinomas (SqCCs) patients have the chance to benefit from novel treatment alternatives, including immune checkpoint blockade and anti-angiogenic agents and, given positive trial results, from afatinib, a second generation tyrosine kinase inhibitor (TKI) that irreversibly antagonizes ErbB family tyrosine kinase receptors. Considering the role of the ErbB-signaling cascade in lung SqCC, it is relevant to note that ErbB1 (epidermal growth factor receptor [EGFR]) is overexpressed in 85% of non-small-cell lung carcinomas (NSCLCs), particularly in patients with squamous histology, and is associated with poor prognosis. For this reason, EGFR activity has been investigated as a therapeutic strategy in lung SqCC. Even taking into account statistically positive trial results, anti-EGFR approach still remains controversial in unselected/wild-type EGFR lung SqCC patients, as well as the optimal timing and sequencing of all available targeted therapies considering the approval of immunotherapeutic agents. This review analyzes current data about EGFR inhibition in lung SqCC with a specific focus on afatinib in order to elucidate available clinical evidence supporting EGFR targeting in this setting as well as a future management of advanced lung SqCCs in the context of new emerging immunotherapeutic drugs.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"9 ","pages":"147-157"},"PeriodicalIF":2.0,"publicationDate":"2017-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S112715","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35240789","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 pomalidomide in patients with relapsed or refractory multiple myeloma with various degrees of impaired renal function.","authors":"Yan Li,&nbsp;Xiaomin Wang,&nbsp;Edward O'Mara,&nbsp;Meletios A Dimopoulos,&nbsp;Pieter Sonneveld,&nbsp;Katja C Weisel,&nbsp;Jeffrey Matous,&nbsp;David S Siegel,&nbsp;Jatin J Shah,&nbsp;Elisabeth Kueenburg,&nbsp;Lars Sternas,&nbsp;Chloe Cavanaugh,&nbsp;Mohamed Zaki,&nbsp;Maria Palmisano,&nbsp;Simon Zhou","doi":"10.2147/CPAA.S144606","DOIUrl":"https://doi.org/10.2147/CPAA.S144606","url":null,"abstract":"<p><p>Pomalidomide is an immunomodulatory drug for treatment of relapsed or refractory multiple myeloma (rrMM) in patients who often have comorbid renal conditions. To assess the impact of renal impairment on pomalidomide exposure, a population pharmacokinetics (PPK) model of pomalidomide in rrMM patients with various degrees of impaired renal function was developed. Intensive and sparse pomalidomide concentration data collected from two clinical studies in rrMM patients with normal renal function, moderately impaired renal function, severely impaired renal function not requiring dialysis, and with severely impaired renal function requiring dialysis were pooled over the dose range of 2 to 4 mg, to assess specifically the influence of the impaired renal function as a categorical variable and a continuous variable on pomalidomide clearance and plasma exposure. In addition, pomalidomide concentration data collected on dialysis days from both the withdrawal (arterial) side and from the returning (venous) side of the dialyzer, from rrMM patients with severely impaired renal function requiring dialysis, were used to assess the extent to which dialysis contributes to the removal of pomalidomide from blood circulation. PPK analyses demonstrated that moderate to severe renal impairment not requiring dialysis has no influence on pomalidomide clearance or plasma exposure, as compared to those patients with normal renal function, while pomalidomide exposure increased approximately 35% in patients with severe renal impairment requiring dialysis on nondialysis days. In addition, dialysis increased total body pomalidomide clearance from 5 L/h to 12 L/h, indicating that dialysis will significantly remove pomalidomide from the blood circulation. Thus, pomalidomide should be administered post-dialysis on the days of dialysis.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"9 ","pages":"133-145"},"PeriodicalIF":2.0,"publicationDate":"2017-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S144606","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35645647","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":"Assessment of prescribed medications and pattern of distribution for potential drug-drug interactions among chronic kidney disease patients attending the Nephrology Clinic of Lagos University Teaching Hospital in Sub-Saharan West Africa.","authors":"Olumuyiwa John Fasipe, Peter Ehizokhale Akhideno, Obiyo Nwaiwu, Alex Adedotun Adelosoye","doi":"10.2147/CPAA.S147835","DOIUrl":"10.2147/CPAA.S147835","url":null,"abstract":"<p><strong>Introduction: </strong>Life expectancy has increased significantly among chronic kidney disease (CKD) patients due to the extensive use of polypharmacy practice for medication prescriptions. This predisposes them to potential drug-drug interactions (DDIs), which can lead to an increase in morbidity, mortality, length of hospital stay, and health care cost.</p><p><strong>Methods: </strong>This was a 30-month retrospective study that reviewed the medical case records of consenting adult CKD patients from January 2014 to June 2016. The Medscape drug reference database was used to evaluate patients' medications for potential DDIs.</p><p><strong>Results: </strong>This study involved 123 adult CKD patients (63 [51.22%] males and 60 [48.78%] females) with a mean age of 53.81±16.03 years. The most common comorbid conditions were hypertension (112 [91.10%]) and diabetes mellitus (45 [36.60%]). Regarding the form of nephrological interventions being offered, the majority of the respondents - 66 (53.66%) were on maintenance dialysis, followed by 53 (43.09%) respondents on conservative care, while 4 (3.25%) respondents were on renal transplantation. A total of 1264 prescriptions were made, and the mean number of prescribed medications per patient was 10.28±3.85. The most frequently prescribed medications were furosemide (88 [71.6%]), heparin (67 [54.47%]), lisinopril (65 [52.9%]), oral calcium carbonate (CaCO₃) (63 [51.2%]), α-calcidol (62 [50.4%]), and erythropoietin (61 [49.6%]). A total number of 1851 potential DDIs were observed among 118 patients. The prevalence of potential DDIs in this study was 78.0%, while the mean DDI per prescription was 1.50. Among the potential DDIs observed, the severity was mild in 639 (34.5%) patients, moderate in 1160 (62.7%) patients, and major in 51 (2.8%) patients and only 1 (0.1%) patient was of contraindicated drug combination. The most frequent DDIs' pattern observed was between oral CaCO₃ and oral ferrous sulfate. There was a statistically significant association between the number of prescribed medications and the estimated glomerular filtration rate (eGFR; pre-ESRD and ESRD staging) with a <i>P</i>-value of 0.00000119. This implies that the number of prescribed medications increases as the eGFR declines in advance CKD stage patients.</p><p><strong>Conclusion: </strong>Most of these interactions have moderate severity and delayed onset, hence the need to follow-up these patients after prescription in order to reduce associated morbidity, mortality, length of hospital stay, and health care cost. Physicians and clinical pharmacists should utilise available interaction software to avoid harmful DDIs in these patients.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"9 ","pages":"125-132"},"PeriodicalIF":2.0,"publicationDate":"2017-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S147835","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35593255","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":"Possible involvement of ROS generation in vorinostat pretreatment induced enhancement of the antibacterial activity of ciprofloxacin.","authors":"Majed M Masadeh,&nbsp;Karem H Alzoubi,&nbsp;Sayer I Al-Azzam,&nbsp;Ahlam M Al-Buhairan","doi":"10.2147/CPAA.S148448","DOIUrl":"https://doi.org/10.2147/CPAA.S148448","url":null,"abstract":"<p><p>The mechanism underlying ciprofloxacin action involves interference with transcription and replication of bacterial DNA and, thus, the induction of double-strand breaks in DNA. It also involves elevated oxidative stress, which might contribute to bacterial cell death. Vorinostat was shown to induce oxidative DNA damage. The current work investigated a possible interactive effect of vorinostat on ciprofloxacin-induced cytotoxicity against a number of reference bacteria. Standard bacterial strains were <i>Escherichia coli</i> ATCC 35218, <i>Staphylococcus aureus</i> ATCC29213, <i>Pseudomonas aeruginosa</i> ATCC 9027, <i>Staphylococcus epidermidis</i> ATCC 12228, <i>Acinetobacter baumannii</i> ATCC 17978, <i>Proteus mirabilis</i> ATCC 12459, <i>Klebsiella pneumoniae</i> ATCC 13883, methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) (ATCC 43300), and <i>Streptococcus pneumoniae</i> (ATCC 25923). The antibacterial activity of ciprofloxacin, with or without pretreatment of bacterial cells by vorinostat, was examined using the disc diffusion procedure and determination of the minimum inhibitory concentration (MIC) and zones of inhibition of bacterial growth. All tested bacterial strains showed sensitivity to ciprofloxacin. When pretreated with vorinostat, significantly larger zones of inhibition and smaller MIC values were observed in all bacterial strains compared to those treated with ciprofloxacin alone. In correlation, generation of reactive oxygen species (ROS) induced by the antibacterial action of ciprofloxacin was enhanced by treatment of bacterial cells with vorinostat. Results showed the possible agonistic properties of vorinostat when used together with ciprofloxacin. This could be related to the ability of these agents to enhance oxidative stress in bacterial cells.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"9 ","pages":"119-124"},"PeriodicalIF":2.0,"publicationDate":"2017-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S148448","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35648751","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}