Clinical Pharmacology : Advances and Applications最新文献

{"title":"Novel approaches to treating advanced systemic mastocytosis","authors":"J. Gilreath, L. Tchertanov, M. Deininger","doi":"10.2147/CPAA.S206615","DOIUrl":"https://doi.org/10.2147/CPAA.S206615","url":null,"abstract":"Abstract Mastocytosis is a myeloproliferative neoplasm characterized by expansion of abnormal mast cells (MCs) in various tissues, including skin, bone marrow, gastrointestinal tract, liver, spleen, or lymph nodes. Subtypes include indolent systemic mastocytosis, smoldering systemic mastocytosis and advanced systemic mastocytosis (AdvSM), a term collectively used for the three most aggressive forms of the disease: aggressive systemic mastocytosis, mast cell leukemia, and systemic mastocytosis with an associated clonal hematological non-mast cell disease (SM-AHNMD). MC activation and proliferation is physiologically controlled in part through stem cell factor (SCF) binding to its cognate receptor, KIT. Gain-of-function KIT mutations that lead to ligand-independent kinase activation are found in most SM subtypes, and the overwhelming majority of AdvSM patients harbor the KITD816V mutation. Several approved tyrosine kinase inhibitors (TKIs), such as imatinib and nilotinib, have activity against wild-type KIT but lack activity against KITD816V. Midostaurin, a broad spectrum TKI with activity against KITD816V, has a 60% clinical response rate, and is currently the only drug specifically approved for AdvSM. While this agent improves the prognosis of AdvSM patients and provides proof of principle for targeting KITD816V as a driver mutation, most responses are partial and/or not sustained, indicating that more potent and/or specific inhibitors are required. Avapritinib, a KIT and PDGFRα inhibitor, was specifically designed to inhibit KITD816V. Early results from a Phase 1 trial suggest that avapritinib has potent antineoplastic activity in AdvSM, extending to patients who failed midostaurin. Patients exhibited a rapid reduction in both symptoms as well as reductions of bone marrow MCs, serum tryptase, and KITD816V mutant allele burden. Adverse effects include expected toxicities such as myelosuppression and periorbital edema, but also cognitive impairment in some patients. Although considerable excitement about avapritinib exists, more data are needed to assess long-term responses and adverse effects of this novel TKI.","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"11 1","pages":"77 - 92"},"PeriodicalIF":2.0,"publicationDate":"2019-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S206615","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48336118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of the pharmacist in improving inhaler technique and asthma management in rural areas in Jordan","authors":"I. Basheti, Y. Salhi, M. Basheti, S. Hamadi, W. Al-Qerem","doi":"10.2147/CPAA.S213271","DOIUrl":"https://doi.org/10.2147/CPAA.S213271","url":null,"abstract":"Introduction Pharmacists can have a valuable role in educating patients on correct inhaler technique leading to improved asthma management. Rural areas can benefit from the role of the pharmacist considering the barriers found in attending primary health-care facilities. Objectives This study aimed to assess the impact of inhaler technique education delivered by pharmacists on patients’ inhaler technique, Asthma Control Test (ACT) score, forced expiratory volume in the first 1 second (FEV1%), and reliever use (puffs/day). Methods A pre–post interventional study was conducted over 6 months from February 2017 to July 2017 in rural areas in Jordan. Asthma patients visiting respiratory clinics and using metered dose inhaler (MDI) or turbuhaler (TH) controlled medication were randomly recruited. Inhaler technique was assessed via published checklists. The ACT, FEV1%, and reliever use (puffs/day) were assessed. Patients were educated on inhaler technique via demonstration with return demonstration education. All assessments were repeated 3 months post education. Results A total of 103 (TH, n=44; MDI, n=59) patients were recruited (mean age=46.5±13.5), 74% females. Patients reported an overuse of their reliever (5.1±4.2 puffs/day). Only 2 patients (1.9%) had well-controlled asthma, while the rest had either moderately (19.4%) or poorly (78.6%) controlled asthma. Patients using the MDI achieved 3.03±4.30 ACT score improvement (p<0.001), which is a clinically significant improvement in control. Patients using the TH achieved a statistically significant improvement of 2.07±4.72 (p=0.031). FEV1% improved significantly for MDI users (p=0.005) but not for TH users (p=0.097). Reliever use decreased significantly for MDI and TH users. Conclusion Asthmatic patients living in rural areas in Jordan reported poor inhaler technique, ACT scores, and FEV1% scores and high use of reliever medications. Pharmacist-led educational intervention resulted in improved inhaler technique scores, ACT scores, and FEV1% scores and lowered reliever use over time.","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"11 1","pages":"103 - 116"},"PeriodicalIF":2.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S213271","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42953695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reproducibility of nasal allergen challenge responses in adults with allergic rhinitis.","authors":"Charles T Pantin,&nbsp;Thomas Southworth,&nbsp;Kristiane Wetzel,&nbsp;Dave Singh","doi":"10.2147/CPAA.S184404","DOIUrl":"https://doi.org/10.2147/CPAA.S184404","url":null,"abstract":"<p><strong>Background: </strong>Allergic rhinitis is characterized by nasal inflammation in response to allergen exposure. Nasal allergen challenges are used in clinical trials evaluating drug effects. Reproducibility of nasal secretion cytokine responses and physiological measurements are needed to determine the optimum measurements and power calculations for future studies. We have investigated the reproducibility of nasal cytokine measurements, using ready-to-use polyvinyl acetate sponges to collect nasal secretions, and measurements of nasal physiological responses.</p><p><strong>Methods: </strong>Twelve subjects with allergic rhinitis and no history of respiratory disease, and 12 subjects with asthma and allergic rhinitis underwent a nasal allergen challenge. This was repeated at 7-14 days later.</p><p><strong>Results: </strong>There were increases in IL-5, CCL11, and CXCL8 responses post-challenge (all <i>P</i><0.05). There was better reproducibility at later time points when higher cytokine levels were detected for IL-5 (<i>r_i</i> =0.64 at 8 hours) and CXCL8 (<i>r_i</i> =0.91 at 8 hours). Acoustic rhinometry provided good to excellent reproducibility (<i>r_i</i> =0.66-0.89). Rhinomanometry had lower reproducibility with greater variation (<i>r_i</i> =0.10-0.70), with some subjects unable to perform the measurement. Multiplex immunoassays provided greater sensitivity for CCL11 measurements. There were no differences between allergic rhinitis patients with and without asthma.</p><p><strong>Conclusion: </strong>Polyvinyl acetate sponges are a practical and reproducible way to sample nasal secretions. Acoustic rhinometry is a practical and reproducible method for assessing physiological responses. There were no differences in nasal response due to the presence of concurrent asthma.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"11 ","pages":"67-76"},"PeriodicalIF":2.0,"publicationDate":"2019-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S184404","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37322512","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":"Current perspective on the role of insulin and glucagon in the pathogenesis and treatment of type 2 diabetes mellitus.","authors":"Ashutosh Ojha,&nbsp;Utkarsh Ojha,&nbsp;Raihan Mohammed,&nbsp;Abhinaya Chandrashekar,&nbsp;Harsh Ojha","doi":"10.2147/CPAA.S202614","DOIUrl":"https://doi.org/10.2147/CPAA.S202614","url":null,"abstract":"<p><p>According to the World Health Organization, 422 million adults worldwide live with diabetes mellitus (DM), a significant portion of whom have type 2 diabetes. The discovery of insulin as a key regulator of glucose metabolism has revolutionized our understanding of DM and provided several therapeutic avenues. Most studies have so far predominantly focused on the role of insulin in type 2 diabetes. However, the balance between insulin and glucagon is essential in ensuring glucose homeostasis. In this review, we begin by evaluating the principal differences between insulin and glucagon with regard to their mechanism and control of their secretion. Next, we discuss their mode of action and effects on metabolism. We further explore how the two hormones impact the natural history of type 2 diabetes. Finally, we outline how current and emerging pharmacological agents attempt to exploit the properties of insulin and glucagon to benefit patients with type 2 diabetes.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"11 ","pages":"57-65"},"PeriodicalIF":2.0,"publicationDate":"2019-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S202614","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37322511","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":"Effects of formulation types on pharmacodynamics of warfarin in patients with cerebral infarction and dysphagia.","authors":"Young-Ji Kim,&nbsp;Jong-Woo Jeong,&nbsp;Youngshin Song,&nbsp;Tae-Sung Koo","doi":"10.2147/CPAA.S184232","DOIUrl":"https://doi.org/10.2147/CPAA.S184232","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to investigate the effects of the type of formulation on the efficacy of warfarin.</p><p><strong>Materials and methods: </strong>The electronic medical records of patients with cerebral infarction, who were administered tablet or powder formulations of warfarin from 2013-2015, were retrospectively analyzed. Clinical data, changes in the international normalized ratio (INR), the warfarin dose, and the time to reach the plasma warfarin concentration that could induce an adverse effect, such as bleeding, were evaluated. Coefficients of variation of INR and of the warfarin dose, as well as the warfarin sensitivity index (WSI), were used to evaluate the INR stability. Statistical analysis of the data was performed using a independent <i>t</i>-test. Additionally, survival analysis was performed.</p><p><strong>Results: </strong>The data showed that 57 and 137 patients were administered warfarin as powder and tablet formulations, respectively. We noted that INR, WSI, and INR/dose × body weight differed significantly between the two groups of patients. The median survival times to reach the plasma warfarin concentration that could induce adverse effects were 3.6 and 4.2 days of treatment with the powder and tablet formulations, respectively. The efficacy of warfarin was higher when the drug was administered as a powder than when it was administered as a tablet.</p><p><strong>Conclusion: </strong>The findings of this study indicate that INR should be carefully monitored in the first 4 days of warfarin administration as a powder formulation.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"11 ","pages":"51-56"},"PeriodicalIF":2.0,"publicationDate":"2019-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S184232","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37111266","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":"Modeling and simulation of the endogenous CYP3A induction marker 4β-hydroxycholesterol during enasidenib treatment.","authors":"Yan Li,&nbsp;Jamie N Connarn,&nbsp;Jian Chen,&nbsp;Zeen Tong,&nbsp;Maria Palmisano,&nbsp;Simon Zhou","doi":"10.2147/CPAA.S192687","DOIUrl":"https://doi.org/10.2147/CPAA.S192687","url":null,"abstract":"<p><strong>Background: </strong>Enasidenib (IDHIFA^®, AG-221) is a first-in-class, targeted inhibitor of mutant IDH2 proteins for treatment of relapsed or refractory acute myeloid leukemia. This was a Phase I/II study evaluating safety, efficacy, and pharmacokinetics/pharmacodynamics (PK/PD) of orally administered enasidenib in subjects with advanced hematologic malignancies with an IDH2 mutation.</p><p><strong>Methods: </strong>Blood samples for PK and PD assessment were collected. A semi-mechanistic nonlinear mixed effect PK/PD model was successfully developed to characterize enasidenib plasma PK and to assess enasidenib-induced CYP3A activity.</p><p><strong>Results: </strong>The PK model showed that enasidenib plasma concentrations were adequately described by a one-compartment model with first-order absorption and elimination; the PD model showed a high capacity to induce CYP3A (E_max=7.36) and a high enasidenib plasma concentration to produce half of maximum CYP3A induction (EC₅₀ =31,400 ng/mL). Monte Carlo simulations based on the final PK/PD model showed that at 100 mg once daily dose there was significant drug accumulation and a maximum of three-fold CYP3A induction after multiple doses. Although the EC₅₀ value for CYP3A induction by enasidenib is high, CYP3A induction was observed due to significant drug accumulation.</p><p><strong>Conclusion: </strong>CYP3A induction following enasidenib dosing should be considered when prescribing concomitant medication metabolized via this pathway.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"11 ","pages":"39-50"},"PeriodicalIF":2.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S192687","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37045039","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":"Assessing the effect of omega-3 fatty acid combined with vitamin D3 versus vitamin D3 alone on estradiol levels: a randomized, placebo-controlled trial in females with vitamin D deficiency.","authors":"Amani H Al-Shaer,&nbsp;Mahmoud S Abu-Samak,&nbsp;Luai Z Hasoun,&nbsp;Beisan A Mohammad,&nbsp;Iman A Basheti","doi":"10.2147/CPAA.S182927","DOIUrl":"https://doi.org/10.2147/CPAA.S182927","url":null,"abstract":"<p><strong>Purpose: </strong>Outcomes investigating the effect of vitamin D3 (VD3) and omega-3 fatty acids (Omega-3FA) on serum estradiol (E2) are scarce and conflicting. No previous study has investigated the effect of VD3 combination with Omega-3FA on E2 levels. This study was designed to investigate the effect of VD3, Omega-3FA and VD3 plus Omega-3FA on serum E2 levels in premenopausal females diagnosed with vitamin D deficiency (VDD).</p><p><strong>Subjects and methods: </strong>This randomized, placebo-controlled clinical trial was designed to evaluate the effects of 50,000 IU VD3 taken weekly, 300 mg Omega-3FA taken daily and their combination by the study participants for 8 weeks. The mid-follicular serum levels of E2 and 25-hydroxy vitamin D (25OHD) were assessed at 8 weeks. The study was conducted during winter on a convenience sample of healthy premenopausal Jordanian females with diagnosed VDD. Fasting serum levels for 25OHD and E2 were assessed at baseline and the end of the trial (after 8 weeks). Data were entered into SPSS and analyzed.</p><p><strong>Results: </strong>Healthy premenopausal Jordanian females (N=86) with diagnosed VDD, mean age 32.8±8.9 years, were recruited into the study. Supplementation of VD3 alone resulted in a significant increase in serum 25OHD (13.4±7.9-28.2±7.1 ng/mL, <i>P</i><0.001) and a significant decrease in E2 levels (85.7±16.5-60.3±20.6 pg/mL, <i>P</i>=0.001). Omega-3FA intake led to a significant decrease in serum 25OHD levels (21.2±12.8-13.6±9.2 ng/mL, <i>P</i>=0.001) and a significant increase in E2 levels (56.3±19.2-78.4±23.7 pg/mL, <i>P</i>=0.006). Combination therapy (VD3 plus Omega-3FA) resulted in a significant increase in both 25OHD (12.0±4.7-35.1±9.5 ng/mL, <i>P</i><0.001) and E2 (43.0±23.4-57.3±31.5 pg/mL, <i>P</i>=0.028) levels.</p><p><strong>Conclusion: </strong>Results of this study provide vital insight into the effects of D3, Omega-3FA and a combination of their supplementation on premenopausal Jordanian females with diagnosed VDD. Eight weeks of therapy led to decreased E2 level by VD3 and increased level by Omega-3FA supplementation. With regard to 25OHD, its level was increased by VD3 and decreased by Omega-3FA supplementation. Combination of VD3 plus Omega-3FA increased the levels of both E2 and 25OHD.</p><p><strong>Trial registration: </strong>This trial was registered at clinicaltrials.gov as NCT03333564.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"11 ","pages":"25-37"},"PeriodicalIF":2.0,"publicationDate":"2019-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S182927","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36578090","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":"Small-cell lung cancer growth inhibition: synergism between NMDA receptor blockade and chemotherapy.","authors":"William G North,&nbsp;Fuli Liu,&nbsp;Konstantin H Dragnev,&nbsp;Eugene Demidenko","doi":"10.2147/CPAA.S183885","DOIUrl":"https://doi.org/10.2147/CPAA.S183885","url":null,"abstract":"<p><strong>Background: </strong>Small-cell lung cancer (SCLC) has a poor prognosis since there is currently no effective therapy for commonly recurring disease. In our previous study, both primary and recurrent human tumors have been shown to express functional <i>N</i>-methyl-D-aspartate (NMDA) receptors, and blockade of these receptors with GluN1 and GluN2B antagonists decreased tumor cell viability in vitro, and growth of tumor xenografts in nu/nu mice.</p><p><strong>Materials and methods: </strong>In this study, we examine the influence of the GluN2B antagonist ifenprodil and the channel-blocker antagonist memantine, on cell viability and growth of tumor xenografts of recurrent SCLC (rSCLC) in mice.</p><p><strong>Results: </strong>Both antagonists significantly reduced cell viability and levels of components of the ERK1/2 pathway, increased apoptosis, and at very safe levels significantly reduced the growth of tumors in mice. Each antagonist and topotecan had additive effects to reduce cell viability with significant synergy demonstrated for the case of memantine. More significantly, combination treatments of xenografts in mice with ifenprodil and the chemotherapeutic agent topotecan produced clear additive effects that completely stopped tumor growth. Moreover, the ifenprodil and topotecan combination showed excellent supra-addition or synergy of inhibition for tumors ≤300 mm in size (<i>P</i>=4.7E-4). Combination treatment of memantine with topotecan also showed clear addition but, unlike ifenprodil, no synergy for the doses chosen.</p><p><strong>Conclusion: </strong>Since topotecan is a drug of choice for treatment of rSCLC, our findings suggest that combining this agent with NMDA receptor blockade using the GluN2B antagonist, ifenprodil, will significantly improve patient outcomes.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"11 ","pages":"15-23"},"PeriodicalIF":2.0,"publicationDate":"2019-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S183885","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36567882","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":"Method development and validation of ursodiol and its major metabolites in human plasma by HPLC-tandem mass spectrometry.","authors":"Márcio Cardoso Pinto,&nbsp;Danilo Chorfi Berton,&nbsp;Alexandre Cavenatti de Oliveira,&nbsp;Carolina Martins Lazaro,&nbsp;Silvana Aparecida Calafatti Carandina","doi":"10.2147/CPAA.S187519","DOIUrl":"https://doi.org/10.2147/CPAA.S187519","url":null,"abstract":"<p><strong>Background: </strong>Ursodeoxycholic acid (UDCA) and its metabolites tauroursodeoxycholic acid (TUDCA) and glycoursodeoxycholic acid (GUDCA) have been the subject of several pharmacological studies. The objective of this study was to develop an innovative method of quantification by HPL-tandem mass spectrometry (LC-MS/MS), with a lower cost and suitable, for application in bioequivalence studies.</p><p><strong>Methods: </strong>The procedure involved liquid-liquid extraction for quantification of UDCA/GUDCA and precipitation extraction for TUDCA, using deuterated substances as internal standards (ISs) and Phenomenex Luna 250×4.6 mm 5μ C₁₈ 100A column. The mobile phase used was acetonitrile/ammonium acetate 30 mM (420: 580 v/v pH 7) for UDCA, acetonitrile/ammonium acetate 10 mM/ammonium hydroxide (400:600: 0.5 v/v/v pH 9) for GUDCA, and acetonitrile/ammonium acetate 10 mM (570: 430 v/v pH 7) for TUDCA. Ions were monitored by the electrospray ion source (ESI) mass spectrometer, operating in a negative ionization mode. Compound determination was performed by LC-MS/MS system using a calibration curve of 15-10,000 ng/mL for UDCA/GUDCA and 5-500 ng/mL for TUDCA. The method was developed and validated according to the Brazilian National Health Surveillance Agency (ANVISA) of Brazil norms harmonized with the main international guidelines as a prerequisite for conducting in vivo study in human volunteers.</p><p><strong>Results: </strong>The method did not present matrix effect and residual effect, showing to be selective for studied molecules, with adequate accuracy and precision. In addition, the method was considered sensitive presenting a coefficient of variation less than 20% for the lower limit of quantification of each compound.</p><p><strong>Conclusion: </strong>This method can be applied in bioequivalence studies to determine ursodiol and its metabolites reproducibly, simply, and effectively with the use of readily accessible analytical materials and instrumentation.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"11 ","pages":"1-13"},"PeriodicalIF":2.0,"publicationDate":"2019-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S187519","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36917385","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":"Correlation between measured and calculated free phenytoin serum concentration in neurointensive care patients with hypoalbuminemia.","authors":"Seyyede-Sareh Javadi,&nbsp;Reza Mahjub,&nbsp;Abbas Taher,&nbsp;Younes Mohammadi,&nbsp;Maryam Mehrpooya","doi":"10.2147/CPAA.S186322","DOIUrl":"https://doi.org/10.2147/CPAA.S186322","url":null,"abstract":"<p><strong>Purpose: </strong>In critically ill patients, monitoring free phenytoin concentration is a valuable method for phenytoin-dosage adjustment. However, due to technical difficulties and the high cost of these methods, the Sheiner-Tozer equation is routinely used for estimating free phenytoin concentration in clinical practice. There have been conflicting results concerning accuracy and precision of the Sheiner-Tozer equation for prediction of free phenytoin concentration in various patient populations. Therefore, this study was conducted to evaluate the accuracy and correlation of measured and calculated free phenytoin concentrations in neurointensive care patients with hypoalbuminemia.</p><p><strong>Methods: </strong>A total of 65 adult neurointensive care patients with hypoalbuminemia who were receiving phenytoin for prevention or treatment of seizures were recruited in this study. In addition to measuring free phenytoin concentration by HPLC, free phenytoin concentration was calculated using both conventional and revised Sheiner-Tozer equations. Eventually, the correlation and level of agreement between measured and calculated free phenytoin concentrations were evaluated.</p><p><strong>Results: </strong>The mean albumin concentration of studied patients was 2.63±0.57 g/dL. There was a significant but weak-moderate correlation between measured and calculated free phenytoin concentration using conventional and revised Sheiner-Tozer equations (<i>r</i>=0.45 and <i>r</i>=0.43, respectively). Conventional and revised Sheiner-Tozer equations were not able to predict free phenytoin concentrations accurately in 33.85% and 35.4% of patients, respectively. Although the sex of patients did not have a significant impact on the level of agreement, younger patients had a higher level of agreement.</p><p><strong>Conclusion: </strong>Although there was a moderate correlation between calculated and measured free phenytoin concentration, the Sheiner-Tozer equation was not able to predict free phenytoin concentration accurately in all patients, especially in older patients. Therefore, monitoring free phenytoin serum concentration besides clinical outcomes should be considered for phenytoin-dose adjustment in critically ill patients.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"10 ","pages":"183-190"},"PeriodicalIF":2.0,"publicationDate":"2018-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S186322","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36817558","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}