Clinical Pharmacology : Advances and Applications最新文献

{"title":"Is Bodyweight-Based Dosing Truly Better Than Flat Dosing for Panitumumab? [Letter].","authors":"Jeroen J M A Hendrikx, Jos H Beijnen, Alwin D R Huitema","doi":"10.2147/CPAA.S282866","DOIUrl":"https://doi.org/10.2147/CPAA.S282866","url":null,"abstract":"1Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; 2Department of Nuclear Medicine, The Netherlands Cancer Institute, Amsterdam, The Netherlands; 3Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands Dear editor With great interest we read the paper by Liao et al in which they compared a 2-weekly bodyweight-based (6 mg/kg) and fixed (480 mg) administration of panitumumab, a monoclonal antibody (Mab) binding the EGFR receptor. The authors used a population pharmacokinetics model to simulate pharmacokinetics of 1200 virtual individuals for each strategy. The observed interpatient variability in mean simulated AUC (CVAUCmean) was compared and was 34% (fixed dosing) versus 29% (bodyweight-based dosing). Based on this, the authors concluded for panitumumab that “body weight-based approach is the recommended patient dosing strategy”. Previously, we assessed feasibility of fixed dosing as an alternative strategy for thirteen Mabs including panitumumab. We concluded that fixed dosing is a more rational approach as pharmacodynamics (efficacy and toxicity) of antagonistic Mabs are not concentration-related at concentrations exceeding the minimum target inhibitory concentration (ICmin). For panitumumab, the estimated threshold is 3.83 μg/mL. The authors compared the CVAUCmean of both dosing strategies. However, because of the ICmin, trough levels (Cmin) would be a better parameter for assessing efficacy of panitumumab. Although the observed Cmin after bodyweight-based dosing is reported (Figure 1 and Discussion), we miss report of simulated Cmin of the fixed dosing schedule. As the lowest interquartile AUC after fixed and bodyweight-based dosing of panitumumab is comparable (987 versus 908 μg*d/ mL, respectively, in Table 2), it is likely that Cmin of the both strategies is comparable (~20–30 μg/mL and »ICmin) and, therefore, both strategies have equivalent efficacy. The reported difference in CVAUCmean for both dosing strategies is mainly caused by the higher exposure of panitumumab in patients with a low bodyweight after fixed dosing (Figure 2). This results in a difference between the highest interquartile AUC after fixed and bodyweight-based dosing (1582 versus 1254 μg*d/mL, respectively in Table 2). However, this is clinically irrelevant as for panitumumab (like most Mabs in oncology), an exposure-toxicity relationship is absent. Although increased incidence of skin toxicity has been reported with increasing doses, this is related to the EGFR inhibition and reaches a plateau at doses of ≥2.5 mg/kg. As onset of ≥grade 2 toxicity is related to better survival and is a result of target inhibition, it even may be evaluated as biomarker for efficacy. In fact, the manufacturer reports that doses up to 12 mg/kg have been used and that the safety profile was consistent with the recommended dose. Since Correspondence: Jeroen JMA Hendrikx Department of ","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"12 ","pages":"177-178"},"PeriodicalIF":2.0,"publicationDate":"2020-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f1/ba/cpaa-12-177.PMC7610198.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38578692","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":"Vitamin D Pretreatment Attenuates Ciprofloxacin-Induced Antibacterial Activity.","authors":"Majed M Masadeh,&nbsp;Karem H Alzoubi,&nbsp;Bashar M Al-Taani,&nbsp;Majd M Masadeh,&nbsp;Zainah O Aburashed,&nbsp;Nasr Alrabadi","doi":"10.2147/CPAA.S268330","DOIUrl":"https://doi.org/10.2147/CPAA.S268330","url":null,"abstract":"<p><strong>Background: </strong>Ciprofloxacin is an antimicrobial that is commonly used to treat several types of infections. It exerts its antimicrobial activity through interfering with bacterial DNA replication and transcription, leading to increase oxidative stress and eventually bacterial death. Vitamin D, on the other hand, has been found to have DNA protective and antioxidant effects. In the current study, the possible interactive effect of vitamin D on ciprofloxacin-induced cytotoxicity was investigated in various standard bacterial strains.</p><p><strong>Methods: </strong>The bacterial strains that were used include <i>Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Staphylococcus epidermidis, Acinetobacter baumannii, Proteus mirabilis</i>, and <i>Klebsiella pneumoniae</i>. The antibacterial effect of ciprofloxacin with and without vitamin D treatment of the bacteria was assessed using disc diffusion method and by measuring the minimum inhibitory concentration (MIC) and zones of inhibition of bacterial growth. Moreover, reactive oxygen species (ROS) generation after pretreatment of <i>E. Coli</i> cells with ciprofloxacin and/or vitamin D was measured as a function of as a function of hydrogen peroxide generation.</p><p><strong>Results: </strong>Ciprofloxacin demonstrated a potent antibacterial effect against the tested strains of bacteria. Moreover, pretreatment with vitamin D resulted in protecting the bacteria from the cytotoxicity of ciprofloxacin, this was indicated by the significantly smaller zones of inhibition and higher MIC values compared to ciprofloxacin alone as well as reduced ciprofloxacin-induced ROS generation after treatment with vitamin D.</p><p><strong>Conclusion: </strong>Results revealed the possible reduction in the activity of ciprofloxacin when used in combination with vitamin D. This could be explained by the ability of vitamin D to reduce oxidative stress in the bacterial cells.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"12 ","pages":"171-176"},"PeriodicalIF":2.0,"publicationDate":"2020-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S268330","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38643093","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":"Hypoglycemic and Antihyperglycemic Activities of 80% Methanol Root Extract of <i>Acanthus polystachyus</i> Delile (Acanthaceae) in Type 2 Diabetic Rats.","authors":"Dagninet Derebe,&nbsp;Muluken Wubetu,&nbsp;Amare Alamirew","doi":"10.2147/CPAA.S273501","DOIUrl":"https://doi.org/10.2147/CPAA.S273501","url":null,"abstract":"<p><strong>Background: </strong>The morbidity and mortality rate from diabetic mellitus are increasing in the world especially in low- and middle-income countries; hence, it is necessary to evaluate the efficacy and safety of medicinal plants to support existing drugs in treating diabetes mellitus. Therefore, the aim of this study was to evaluate the hypoglycemic effect of 80% methanol root extract of <i>Acanthus polystachyus</i> in normoglycemic, hyperglycemic, and streptozotocin-nicotinamide induced diabetic rats.</p><p><strong>Methods: </strong>Male albino Wistar rats were divided into five groups (n=6) in all three models. In all models, group one rats served as a negative control and were received vehicle (10mL/kg distilled water), whereas group two (APRE100), three (APRE200), and four (APRE400) were treated with 100, 200, and 400mg/kg of extract, respectively, and group five were treated with glibenclamide (5mg/kg) and served as a positive control. Blood glucose levels were measured at different time points by taking blood from their tails. Data were analyzed using one-way ANOVA followed by Tukey's post hoc test to carry out comparisons between and within-group and P < 0.05 was considered as statistically significant.</p><p><strong>Results: </strong>The root of <i>Acanthus polystachyus</i> reduces peak blood sugar levels significantly after the loading of oral glucose at all tested doses. In streptozotocin-nicotinamide-induced type 2 diabetic rats, the daily oral administration of the crude extracts showed a significant reduction of blood glucose level at all tested doses compared to the negative control group. However, the extract did not reduce blood glucose levels in normoglycemic rats at all tested doses compared to both negative and positive control.</p><p><strong>Conclusion: </strong>From this study, it can be concluded that the root extract of <i>Acanthus polystachyus</i> showed an antihyperglycemic effect in hyperglycemic and diabetic rats but lack hypoglycemic effect in normoglycemic rats. Hence, the plant root may be a good candidate for the development of new antidiabetic drugs.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"12 ","pages":"149-157"},"PeriodicalIF":2.0,"publicationDate":"2020-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S273501","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38492509","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":"Magnesium Sulfate Improves Some Risk Factors for Atherosclerosis in Patients Suffering from One or Two Coronary Artery Diseases: A Double-blind Clinical Trial Study.","authors":"Ali Reza Sobhani,&nbsp;Hossein Farshidi,&nbsp;Fariba Azarkish,&nbsp;Mahdiya Eslami,&nbsp;Ebrahim Eftekhar,&nbsp;Mansoor Keshavarz,&nbsp;Nepton Soltani","doi":"10.2147/CPAA.S261264","DOIUrl":"https://doi.org/10.2147/CPAA.S261264","url":null,"abstract":"<p><strong>Purpose: </strong>Given the beneficial effect of MgSO₄ on the cardiovascular system, this study was designed to investigate the effect of MgSO₄ administration on suppressing some atherosclerotic risk factors in moderate coronary artery disease patients with one or two atherosclerotic vessels.</p><p><strong>Patients and methods: </strong>In a randomized double-blind placebo-controlled clinical trial study, 64 patients with moderate coronary artery disease (55-69% stenosis) were selected according to angiography findings. Patients were divided into four groups including patients with one or two atherosclerotic vessels treated with MgSO₄ (Mg-treated-VR1, Mg-treated-VR2, respectively), placebo treated patients with one or two atherosclerotic vessels (Control-VR1, Control-VR2, respectively). The patients received either placebo or MgSO₄ supplement capsule containing 300 mg MgSO₄ for six months on a daily basis. ESR, Ca/Mg ratio, urine Mg level, serum Mg, fibrinogen, homocysteine, uric acid, Na, K, Ca, CRP, T3, T4, TSH, BUN, and Cr concentrations were measured at baseline and every three months.</p><p><strong>Results: </strong>Serum T3, Ca, K, homocysteine, CRP, and Mg concentrations were significantly improved in Mg-treated groups compared to placebo groups.</p><p><strong>Conclusion: </strong>The results of this study showed that despite the slight change in serum magnesium level, oral administration of MgSO₄for six months could slightly reduce the serum levels of some inflammatory and vascular factors in moderate coronary artery disease patients.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"12 ","pages":"159-169"},"PeriodicalIF":2.0,"publicationDate":"2020-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S261264","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38492510","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":"Predicted Efficacy of Once-Daily Extended-Release Oxcarbazepine (Oxtellar XR^®) Monotherapy in Adults and Children with Partial-Onset Seizures: Exposure-Response Modeling and Simulation.","authors":"Shamia Faison, Roberto Gomeni, Shannon Mendes, Welton O'Neal, Stefan Schwabe, Azmi Nasser","doi":"10.2147/CPAA.S256972","DOIUrl":"10.2147/CPAA.S256972","url":null,"abstract":"<p><strong>Purpose: </strong>We conducted exposure-response modeling and simulations to compare the predicted efficacy of extended-release oxcarbazepine (OXC-XR), an oral once-daily (qd) antiepileptic drug, with that of immediate-release (IR) OXC twice-daily (bid) when the agents are used as monotherapy or adjunctive therapy in patients with epilepsy characterized by partial-onset seizures (POS).</p><p><strong>Methods: </strong>Modeling assessed percent change from baseline 28-day seizure frequency (PCH) as a function of minimum concentration (C_min) of monohydroxy derivative (MHD), the clinically relevant metabolite of OXC. For OXC-IR, the model used historical data; values for OXC-XR were derived from observed data. The model was simulated (N=100) to predict PCH at MHD C_min concentrations achieved with 1200 and 2400 mg/day in adults and children receiving OXC-XR qd or OXC-IR bid. Mean PCH and 95% confidence intervals (CIs) were generated and compared.</p><p><strong>Results: </strong>Predicted efficacy was not different (ie, 95% CI of mean PCH overlapped) for OXC-XR qd vs OXC-IR bid at mean MHD C_min concentrations achieved with 1200 and 2400 mg/day adjunctive OXC-XR (47.4 and 76.4 µmol/L) and at target MHD C_min concentrations for OXC-IR monotherapy (59.1 and 112 µmol/L) in adults. Predicted efficacy in adults vs children was not different between formulations. Depending on MHD C_min, the predicted mean PCH in adults ranged from -51.4% to -73.4% with OXC-XR qd and -53.2% to -78.5% with OXC-IR bid. In children, the predicted mean PCH ranged from -48.4% to -58.1% (OXC-XR qd) and -32.5% to -70.4% (OXC-IR bid).</p><p><strong>Conclusion: </strong>This model-based analysis predicted comparable efficacy for OXC-XR qd vs OXC-IR bid at MHD C_min concentrations corresponding to 1200 and 2400 mg/day as monotherapy or adjunctive therapy. Based on this analysis, the US Food & Drug Administration approved OXC-XR for use as monotherapy in adults and children ≥6 years of age with POS.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"12 ","pages":"135-147"},"PeriodicalIF":2.0,"publicationDate":"2020-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S256972","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38492508","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":"Reduced Prescription of Baloxavir After Suspected Prevalence of a Baloxavir-Resistant Influenza Virus Strain and the Emergence of SARS-CoV-2 in a Tertiary Hospital in Japan.","authors":"Yasuhiro Kamioka,&nbsp;Shota Kashiwagura,&nbsp;Masafumi Seki","doi":"10.2147/CPAA.S268666","DOIUrl":"https://doi.org/10.2147/CPAA.S268666","url":null,"abstract":"<p><strong>Objective: </strong>The use of baloxavir, a new anti-influenza agent, began in Japan from the 2018 to 2019 season and became the focus of attention due to its efficient viral reduction ability; therefore, we should know the prescription changes of anti-influenza agents.</p><p><strong>Methods: </strong>We analyzed the changes in the prescription of anti-influenza agents between the 2018-19 season and the 2019-20 season in our hospital.</p><p><strong>Results: </strong>The share of baloxavir was 15%, while the shares of oseltamivir and laninamivir were 42% and 31%, respectively in the 2018-2019 season. However, in the 2019-20 season, the share of baloxavir and laninamivir was reduced to 3% and 17%, respectively, in contrast to an increase in the share of oseltamivir (66%). The total prescription of anti-influenza agents for patients decreased in the 2019-20 season (205 patients), compared with the 2018-19 season (509 patients).</p><p><strong>Conclusion: </strong>These results suggest significant changes such as a reduction in the prescription of anti-influenza agents, especially baloxavir, likely due to the suspected prevalence of a baloxavir-resistant strain of influenza virus and the emergence of SARS-CoV-2 in Japan.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"12 ","pages":"131-134"},"PeriodicalIF":2.0,"publicationDate":"2020-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S268666","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38375627","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 Efficacy and Safety of Low Dose versus Usual Dose of Hyoscine During Endoscopic Retrograde Cholangiopancreatography: A Randomized Clinical Trial.","authors":"Hassan Salmanroghani,&nbsp;Massoud Mirvakili,&nbsp;Mahtabalsadat Mirjalili,&nbsp;Mahmud Baghbanian,&nbsp;Roham Salmanroghani","doi":"10.2147/CPAA.S263531","DOIUrl":"https://doi.org/10.2147/CPAA.S263531","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the efficacy and safety of low dose versus usual dose of Hyoscine during endoscopic retrograde cholangiopancreatography (ERCP).</p><p><strong>Patients and methods: </strong>This randomized, open-label clinical trial included 282 patients undergoing ERCP who had duodenal peristalsis interfering with cannulation. Patients were randomly divided into two groups: Group one and two received low (5 mg) and usual (10 mg) dose of Hyoscine, respectively. Cardiovascular service consultation was performed for all patients before entering the study and performing ERCP. Hyoscine was injected intravenously, and the spasmolytic effect of the drug was assessed while the papilla was in a completely enface view. The time interval between cessation of peristalsis and its further onset was recorded by the chronometer. Also, patient's heart rate and blood pressure were monitored during ERCP by digital monitoring.</p><p><strong>Results: </strong>The results showed no statistically significant differences in the mean duration of peristalsis, the duration of the antispasmodic activity and the time required to increase the heart rate between two groups (P=0.38, P=0.48, P=0.32, respectively). No significant differences were observed regarding the average of heart rate and mean arterial blood pressure (MAP) before drug administration between the two groups (P=0.182 and P=0.29, respectively), but after the drug administration, tachycardia and hypotension were significantly higher in the second group (P=0.007 and P=0.001, respectively). There was no statistically significant difference in the frequency of arrhythmia between two groups (P=0.08). The results also showed that tachycardia and hypotension occurred more frequently in men and elderly patients (P <0.05).</p><p><strong>Conclusion: </strong>A low dose of Hyoscine is as effective as the usual dose and its side effects such as alteration in blood pressure and heart rate are much fewer, especially in men and elderly patients.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"12 ","pages":"123-130"},"PeriodicalIF":2.0,"publicationDate":"2020-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S263531","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38358603","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":"Hydroxychloroquine in COVID-19: The Study Points to Premature Decisions on Efficacy While Bells Ringing for Safety.","authors":"Sitaram Khadka, Dhan Bahadur Shrestha, Pravash Budhathoki, Era Rawal","doi":"10.2147/CPAA.S269156","DOIUrl":"10.2147/CPAA.S269156","url":null,"abstract":"<p><p>Coronavirus disease (COVID-19) pandemic has been a global disease burden. It has affected more than sixteen million people in the world within seven months of its first outbreak in Wuhan. Different treatment modalities, therapeutic and prophylactic agents for its therapy are underway. Until the proven therapy gets available, repurposing of drugs is a better way out. Hydroxychloroquine (HCQ) has been a potential recourse of treatment in this regard for COVID-19 management. As different episodes of cardiac adverse events of HCQ are reported, safety concerns are now a prime objective. The risk-benefit analysis is mandatory to address rational drug therapy even in such a global health crisis. In this article, we want to evaluate the safety and efficacy of HCQ in COVID-19 management.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"12 ","pages":"115-121"},"PeriodicalIF":2.0,"publicationDate":"2020-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f1/1b/cpaa-12-115.PMC7450277.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38456622","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":"Dose Regimen Rationale for Panitumumab in Cancer Patients: To Be Based on Body Weight or Not.","authors":"Michael Z Liao,&nbsp;Marloes Berkhout,&nbsp;Hans Prenen,&nbsp;Sandeep Dutta,&nbsp;Vijay V Upreti","doi":"10.2147/CPAA.S262949","DOIUrl":"https://doi.org/10.2147/CPAA.S262949","url":null,"abstract":"<p><strong>Introduction: </strong>Body weight can affect exposure, safety and efficacy of antibody-based therapies; sometimes these effects may not be clinically relevant. Panitumumab is approved for wild-type <i>RAS</i> metastatic colorectal cancer, using a body weight-based dosing regimen. Recently, a report cited fixed-dose usage of panitumumab, rather than approved body weight-based dosing. The current work evaluates optimal dosing regimen scientifically based on clinical data, modeling and simulation. Herein, we assessed the effect of fixed and body weight-based dosing on panitumumab pharmacokinetics to determine which approach resulted in the least interpatient pharmacokinetic variability.</p><p><strong>Patients and methods: </strong>From the Vectibix program, 352 patients enrolled in three studies were evaluated; they had received panitumumab (body weight-based dose: 6 mg/kg every 2 weeks) and had pharmacokinetic (maximum serum [C_max] and trough [C_min] concentrations) and body weight data available. Additionally, concentration-time profiles at fixed (480 mg) and body weight-based doses (6 mg/kg) were simulated using a population pharmacokinetics model developed from 1200 patients.</p><p><strong>Results: </strong>After administration of panitumumab 6 mg/kg, C_max and C_min increased with increasing body weight; the mean C_max and C_min for patients weighing <65 kg (lower quartile) were 23% and 30% lower, respectively, than for those weighing >88 kg (upper quartile). The simulated area under the concentration-time curve (AUC) data also indicated that overall panitumumab exposure increased with increasing body weight for the body weight-based regimen. When AUC was simulated for a fixed dose (480 mg), the opposite effect was observed. Over the range of body weights, interpatient variability in simulated AUC was lower for the weight-based dose (29%) than for the fixed dose (34%).</p><p><strong>Conclusion: </strong>Results demonstrate that the weight-based dose (6 mg/kg) reduced variability in panitumumab exposure across the range of body weights compared with the fixed-dose approach, indicating that a body weight-based approach is the recommended patient dosing strategy.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"12 ","pages":"109-114"},"PeriodicalIF":2.0,"publicationDate":"2020-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S262949","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38278460","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":"Inhibitors of the Autotaxin-Lysophosphatidic Acid Axis and Their Potential in the Treatment of Interstitial Lung Disease: Current Perspectives.","authors":"Sabrina Zulfikar,&nbsp;Sarah Mulholland,&nbsp;Huzaifa Adamali,&nbsp;Shaney L Barratt","doi":"10.2147/CPAA.S228362","DOIUrl":"https://doi.org/10.2147/CPAA.S228362","url":null,"abstract":"<p><p>Idiopathic pulmonary fibrosis is a progressive fibrosing interstitial lung disease for which there is no known cure. Currently available therapeutic options have been shown at best to slow the progression of the disease and thus there remains an urgent unmet need to identify new therapies. In this article, we will discuss the mechanisms of action, pre-clinical and clinical trial data surrounding inhibitors of the autotaxin-lysophosphatidic acid axis, which show promise as emerging novel therapies for fibrotic lung disease.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"12 ","pages":"97-108"},"PeriodicalIF":2.0,"publicationDate":"2020-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S228362","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38248144","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}