{"title":"Predicted Efficacy of Once-Daily Extended-Release Oxcarbazepine (Oxtellar XR<sup>®</sup>) 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<sub>min</sub>) 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<sub>min</sub> 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<sub>min</sub> concentrations achieved with 1200 and 2400 mg/day adjunctive OXC-XR (47.4 and 76.4 µmol/L) and at target MHD C<sub>min</sub> 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<sub>min</sub>, 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<sub>min</sub> 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, Shota Kashiwagura, 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}
Hassan Salmanroghani, Massoud Mirvakili, Mahtabalsadat Mirjalili, Mahmud Baghbanian, Roham Salmanroghani
{"title":"The Efficacy and Safety of Low Dose versus Usual Dose of Hyoscine During Endoscopic Retrograde Cholangiopancreatography: A Randomized Clinical Trial.","authors":"Hassan Salmanroghani, Massoud Mirvakili, Mahtabalsadat Mirjalili, Mahmud Baghbanian, 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}
Sitaram Khadka, Dhan Bahadur Shrestha, Pravash Budhathoki, Era Rawal
{"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}
Michael Z Liao, Marloes Berkhout, Hans Prenen, Sandeep Dutta, Vijay V Upreti
{"title":"Dose Regimen Rationale for Panitumumab in Cancer Patients: To Be Based on Body Weight or Not.","authors":"Michael Z Liao, Marloes Berkhout, Hans Prenen, Sandeep Dutta, 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<sub>max]</sub> and trough [C<sub>min</sub>] 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<sub>max</sub> and C<sub>min</sub> increased with increasing body weight; the mean C<sub>max</sub> and C<sub>min</sub> 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}
Sabrina Zulfikar, Sarah Mulholland, Huzaifa Adamali, Shaney L Barratt
{"title":"Inhibitors of the Autotaxin-Lysophosphatidic Acid Axis and Their Potential in the Treatment of Interstitial Lung Disease: Current Perspectives.","authors":"Sabrina Zulfikar, Sarah Mulholland, Huzaifa Adamali, 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}
{"title":"Pharmacokinetic Disposition Difference Between Cyclosporine and Voclosporin Drives Their Distinct Efficacy and Safety Profiles in Clinical Studies.","authors":"Yan Li, Maria Palmisano, Duxin Sun, Simon Zhou","doi":"10.2147/CPAA.S255789","DOIUrl":"https://doi.org/10.2147/CPAA.S255789","url":null,"abstract":"<p><strong>Background: </strong>Voclosporin, a more potent derivative of cyclosporine, has been studied extensively in patients with immunologic disorders such as psoriasis, organ transplantation, uvetitis and lupus nephritis. Although better tolerated and safer than cyclosporine, voclosporin is inferior to cyclosporine in treating psoriasis, non-inferior to tacrolimus in organ transplantation and efficacious in treating lupus nephritis.</p><p><strong>Methods: </strong>The pharmacokinetic dispositions of voclosporin and cyclosporine in central and peripheral compartments were analyzed and correlated with their distinct clinical efficacy and safety profiles.</p><p><strong>Results: </strong>Both drugs demonstrated non-linear pharmacokinetics with increasing doses, more prominently at lower doses of voclosporin than at 10-fold higher doses of cyclosporine. Repeated lower dosing of voclosporin produced preferential calcineurin inhibition in and near blood circulation, leading to relatively lower cardiovascular and renal adverse effects but inferior efficacy for psoriasis compared to cyclosporine. With 10-fold higher plasma levels and deeper tissue penetration, cyclosporine has more prevalent renal and cardiac toxicities but superior efficacy to treat psoriasis.</p><p><strong>Conclusion: </strong>Although the two drugs are similar in structure and mechanism of action, the high potency and low dose compounded by the non-linear disposition of voclosporin resulted in more systemic versus local calcineurin inhibition than with cyclosporine. The dispositional difference between voclosporin and cyclosporine accounted for the puzzling efficacy and safety observations in different patients and was the basis for their optimal and differential use in treating diverse immunologic disorders.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"12 ","pages":"83-96"},"PeriodicalIF":2.0,"publicationDate":"2020-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S255789","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38156552","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}
Farzad Allameh, Abbas Basiri, Mohammadreza Razzaghi, Amir Reza Abedi, Morteza Fallah-Karkan, Saleh Ghiasy, Seyyed Mohammad Hosseininia, Saeed Montazeri
{"title":"Clinical Efficacy of Transurethral Resection of the Prostate Combined with Oral Anticholinergics or Botulinum Toxin - A Injection to Treat Benign Prostatic Hyperplasia with Overactive Bladder: A Case-Control Study.","authors":"Farzad Allameh, Abbas Basiri, Mohammadreza Razzaghi, Amir Reza Abedi, Morteza Fallah-Karkan, Saleh Ghiasy, Seyyed Mohammad Hosseininia, Saeed Montazeri","doi":"10.2147/CPAA.S256051","DOIUrl":"https://doi.org/10.2147/CPAA.S256051","url":null,"abstract":"<p><strong>Introduction: </strong>Recent investigations showed that anticholinergic drugs could use for the management of storage symptoms after transurethral resection of the prostate (TURP). The use of intravesical botulinum toxin-A (BTX-A) for the management of overactive bladder is rapidly increasing. In this research, we assess the efficacy of BTX-A vs solifenacin in men suffering from bladder outlet obstruction-over active bladder (BOO-OAB) managed with TURP.</p><p><strong>Methods: </strong>In this case-control study, 50 men with BOO-OAB randomized into two groups. The control group (A) underwent TURP and subsequently managed by solifenacin 5 mg daily, and the case group (B) underwent TURP and BTX-A injection in the bladder wall in the same session. Treatment success was the primary outcome and defined as post-injection improvement in the storage score of the International Prostate Symptom Score (IPSS) from baseline.</p><p><strong>Results: </strong>The IPSS, post-void residual volume, frequency, incomplete emptying, nocturia and urgency subscores considerably ameliorated after 12 weeks and 36 weeks for both groups, but it was more significant in the case arm. The quality of life (QoL) scores significantly improved after the treatments in both groups. Intervention group showed significant reductions regarding urgency incontinence compared with the solifenacin group at 12th and 36th weeks.</p><p><strong>Conclusion: </strong>BTX-A is an effective and well-tolerated treatment in patients with benign prostatic hyperplasia (BPH) who are candidates of TURP and simultaneously suffer from OAB symptoms.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"12 ","pages":"75-81"},"PeriodicalIF":2.0,"publicationDate":"2020-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S256051","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38118150","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":"Phytochemical and Antiulcer Activity Screening of Seed Extract of <i>Cordia africana</i> Lam (Boraginaceae) in Pyloric Ligated Rats.","authors":"Yazachew Engida Yismaw, Mohammedbrhan Abdelwuhab, Digambar B Ambikar, Ayenew Engida Yismaw, Dagninet Derebe, Wondim Melkam","doi":"10.2147/CPAA.S245672","DOIUrl":"https://doi.org/10.2147/CPAA.S245672","url":null,"abstract":"<p><strong>Introduction: </strong>Peptic ulcer disease represents a worldwide health problem because of its high morbidity, mortality and economic loss. It is a very prevalent condition affecting around 10%-15% of the general population worldwide. Most of the available antiulcer drugs are costly and have an incidence of relapse, drug interactions and several side effects upon chronic usage. Hence, the use of herbal medicine may be safe, economical and effective in such cases when drugs are used for long periods. Ethnobotanical reports showed traditional claims on the use of <i>Cordia africana</i> seeds for the treatment of gastric ulcers. However, the safety and efficacy of these remedies are not well known. The aim of this study is, therefore, to evaluate the antiulcer activity and safety of a crude extract of <i>C. africana</i> seeds in animal models.</p><p><strong>Methods: </strong>Shade-dried seeds of <i>C. africana</i> were extracted by 80% methanol and dried by the rotator evaporator and lyophilized. The crude extract was used to evaluate antiulcer activity in vivo with pylorus ligation method, on Wistar albino rats weighing 230-250g. Preliminary phytochemical screening was performed using a standard procedure. Acute toxicity study was carried out in Swiss albino mice before antiulcer activity tests.</p><p><strong>Results: </strong>No sign of toxicity was observed upon the administration of 2000 mg/kg of the crude extract to mice. Single-dose administration of 400 and 600 mg/kg extract showed a significant reduction in the volume of secretion and acidity of the stomach (p <0.01). The doses 400 and 600 mg/kg have reduced the ulcer score by 83.58% and 88%.</p><p><strong>Conclusion: </strong>The result of this study showed that the hydromethanolic crude extract of <i>C. africana</i> has strong antisecretory and ulcer protective activities against ulcers produced by pylorus ligation.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"12 ","pages":"67-73"},"PeriodicalIF":2.0,"publicationDate":"2020-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S245672","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38128783","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}
Negar Firouzabadi, Maral Haghnegahdar, Bahman Khalvati, Ali Dehshahri, Ehsan Bahramali
{"title":"Overexpression of Adiponectin Receptors in Opium Users with and without Cancer.","authors":"Negar Firouzabadi, Maral Haghnegahdar, Bahman Khalvati, Ali Dehshahri, Ehsan Bahramali","doi":"10.2147/CPAA.S256289","DOIUrl":"https://doi.org/10.2147/CPAA.S256289","url":null,"abstract":"<p><strong>Aim: </strong>Opium addiction is a serious public health concern in the Middle East countries causing various illnesses. Opium use is associated with an increased risk of several cancers; however, the underlying mechanisms are not yet fully elucidated. Altered levels of adiponectin and its related main receptors, Adiponectin receptor 1 and 2 (AdipoR1 and AdipoR2) have been associated with several malignancies. Opium users are at risk of various cancers. All together let us to the hypothesis that probable overexpression of AdipoRs in opium users might be linked to the occurrence of cancer in this population.</p><p><strong>Methods: </strong>One hundred opium users along with 100 healthy non-opium users were enrolled in the study. Opium users were followed up for 5 years (2014-2019) to evaluate the occurrence of malignancies. AdipoR1 and AdipoR2 expressions were measured using a flow cytometry method.</p><p><strong>Results: </strong>Expression of AdipoR1 and AdipoR2 was significantly higher in opium users compared with the healthy control group (P=0.0001 and 0.0001, respectively). Eight opium users developed cancer during the follow-up period. Subjects abusing opium developed cancer by 8.6 folds comparing to non-opium users (P=0.034; OR=8.6; 95% CI (1.06-70.1)). Expression of these two receptors was significantly higher in opium users developing cancer compared with cancer-free opium (P=0.001).</p><p><strong>Conclusion: </strong>Considering the significant overexpression of AdipoR1 and AdipoR2 in opium users and in opium users who developed malignancies and the association between upregulation of these receptors in most cancers affecting opium users and assessment of AdipoRs may serve as an early detection tool of cancer in this population.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"12 ","pages":"59-65"},"PeriodicalIF":2.0,"publicationDate":"2020-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S256289","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38109405","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}