Clinical Pharmacology : Advances and Applications最新文献

{"title":"Practical recommendations for the use of therapeutic drug monitoring of biopharmaceuticals in inflammatory diseases.","authors":"Erwin Dreesen,&nbsp;Peter Bossuyt,&nbsp;Denis Mulleman,&nbsp;Ann Gils,&nbsp;Dora Pascual-Salcedo","doi":"10.2147/CPAA.S138414","DOIUrl":"https://doi.org/10.2147/CPAA.S138414","url":null,"abstract":"<p><p>Biopharmaceuticals directed against tumor necrosis factor-alpha, integrins, interleukins, interferons and their receptors have become key agents for the management of inflammatory diseases in the fields of gastroenterology, rheumatology, dermatology and neurology. However, response to these treatments is far from optimal. Therapeutic failure has been attributed in part to inadequate serum concentrations of the drug and the formation of antidrug antibodies (ADA). Therapeutic drug monitoring (TDM) based on drug concentrations and ADA represents a pharmacologically sound tool for guiding dosage adjustments to optimize exposure. Although becoming standard practice in tertiary care centers, the widespread accessibility and recognition of TDM is hindered by several hurdles, including a lack of education of health care providers on TDM. In this paper, the Monitoring of monoclonal Antibodies Group in Europe (MAGE) provides an introduction on the fundamental principles of the concept of TDM, aiming to educate clinicians and assist them in the process of implementing TDM of anti-inflammatory biopharmaceuticals.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"9 ","pages":"101-111"},"PeriodicalIF":2.0,"publicationDate":"2017-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S138414","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35524119","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":"Antipsychotic prescription to identify delirium: results from two cohorts.","authors":"Kristin M Zimmerman,&nbsp;Allison M Paquin,&nbsp;James L Rudolph","doi":"10.2147/CPAA.S138441","DOIUrl":"https://doi.org/10.2147/CPAA.S138441","url":null,"abstract":"<p><strong>Objectives: </strong>Detection of delirium in hospitalized patients remains challenging. The objective was to determine if the prescription of antipsychotic medications was associated with delirium.</p><p><strong>Patients and methods: </strong>Two patient cohorts were utilized from a tertiary Veterans Affairs hospital: a palliative care retrospective cohort and a prospective medical cohort. Patients prescribed outpatient antipsychotics were excluded. Retrospectively, delirium was identified using a validated medical record-review instrument. Prospectively, a clinical expert assessed patients for delirium daily using a standardized interview. Acute antipsychotic medication administration was recorded from the electronic medical record.</p><p><strong>Results: </strong>In the retrospective cohort (n=217), delirium was found in 31% (n=67) and antipsychotic use in 18% (n=40) of patients. Acute antipsychotic use indicated delirium with 54% sensitivity and 97% specificity. In the prospective cohort (n=100), delirium developed in 23% (n=23) and antipsychotics were used in 5% (n=5) of patients. The sensitivity and specificity of acute antipsychotic use was 22% and 100%, respectively.</p><p><strong>Conclusion: </strong>Hospitalized patients who are acutely prescribed antipsychotics are likely to have delirium, but not all patients with delirium will be identified with this method. In health systems, utilization of the prescription of acute antipsychotics can be an efficient and specific method to identify delirious patients for targeted intervention.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"9 ","pages":"113-117"},"PeriodicalIF":2.0,"publicationDate":"2017-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S138441","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35524120","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":"Etanercept (Enbrel^®) alternative storage at ambient temperature.","authors":"Edel Shannon, Joanne Daffy, Heather Jones, Andrea Paulson, Steven M Vicik","doi":"10.2147/CPAA.S131832","DOIUrl":"10.2147/CPAA.S131832","url":null,"abstract":"<p><strong>Background: </strong>Biologic disease-modifying antirheumatic drugs, including tumor necrosis factor inhibitors such as etanercept (Enbrel^®), have improved outcomes for patients with rheumatic and other inflammatory diseases, with sustained remission being the optimal goal for patients with rheumatoid arthritis. Flexible and convenient treatment options, compatible with modern lifestyle, are important in helping patients maintain treatment and manage their disease. Etanercept drug product (DP) is available in lyophilized powder (Lyo) for solution injection, prefilled syringe, and prefilled pen presentations and is typically stored under refrigerated conditions. We aimed to generate a comprehensive analytical data package from stability testing of key quality attributes, consistent with regulatory requirements, to determine whether the product profile of etanercept is maintained at ambient temperature.</p><p><strong>Methods: </strong>Test methods assessing key attributes of purity, quality, potency, and safety were performed over time, following storage of etanercept DP presentations under a range of conditions.</p><p><strong>Results: </strong>Results and statistical analysis from stability testing (based on size exclusion high-performance liquid chromatography, hydrophobic interaction chromatography, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis Coomassie) across all etanercept presentations (10 and 25 mg/vial Lyo DP; 25 and 50 mg prefilled syringe DP; 50 mg prefilled pen DP) showed key stability-indicating parameters were within acceptable limits through the alternative storage condition of 25°C±2°C for 1 month.</p><p><strong>Conclusion: </strong>Stability testing performed in line with regulatory requirements supports a single period of storage for etanercept DP at an alternative storage condition of 25°C±2°C for up to 1 month within the approved expiry of the product. This alternative storage condition represents further innovation in the etanercept product lifecycle, providing greater flexibility and enhanced overall convenience for patients.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"9 ","pages":"87-99"},"PeriodicalIF":2.0,"publicationDate":"2017-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/00/8b/cpaa-9-087.PMC5531722.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35303923","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":"NMDA receptors are important regulators of pancreatic cancer and are potential targets for treatment.","authors":"William G North,&nbsp;Fuli Liu,&nbsp;Liz Z Lin,&nbsp;Ruiyang Tian,&nbsp;Bonnie Akerman","doi":"10.2147/CPAA.S140057","DOIUrl":"https://doi.org/10.2147/CPAA.S140057","url":null,"abstract":"<p><p>Pancreatic cancer, particularly adenocarcinoma of the pancreas, is a common disease with a poor prognosis. In this study, the importance of N-methyl-D-aspartate (NMDA) receptors for the growth and survival of pancreatic cancer was investigated. Immunohistochemistry performed with antibodies against GluN1 and GluN2B revealed that all invasive adenocarcinoma and neuroendocrine pancreatic tumors likely express these two NMDA receptor proteins. These proteins were found to be membrane components of pancreatic cancer cell lines, and both channel-blocker antagonist and GluN2B antagonist significantly reduced cell viability in vitro. Both types of antagonists caused an internalization of the receptors. Dizocilpine maleate (MK-801) and ifenprodil hemitartrate both significantly inhibited the growth of pancreatic tumor xenografts in nu/nu mice. These findings predict that, as for other solid tumors investigated by us, pancreatic cancer could be successfully treated, alone or in combination, with NMDA receptor antagonists or other receptor-inhibiting blocking agents.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"9 ","pages":"79-86"},"PeriodicalIF":2.0,"publicationDate":"2017-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S140057","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35280322","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":"Adverse reactions in leprosy patients who underwent dapsone multidrug therapy: a retrospective study.","authors":"Sanjeev Guragain,&nbsp;Namrata Upadhayay,&nbsp;Bishwa Mohan Bhattarai","doi":"10.2147/CPAA.S135846","DOIUrl":"https://doi.org/10.2147/CPAA.S135846","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the occurrence and clinical characteristics of dapsone-related adverse drug reactions (ADRs) among leprosy patients who underwent multidrug therapy (MDT) from 2010 to 2013 in the western region of Nepal.</p><p><strong>Methods: </strong>A retrospective review was carried out in the rehabilitation center. Data were collected from the record files of the hospital.</p><p><strong>Results: </strong>From 2010 to 2013, there were 18 patients reported to have dapsone ADRs, with an occurrence rate of 0.82% in the 4-year duration. The maximum incidence of ADRs (1.043%) was in 2010 and the minimum incidence of ADRs (0.26%) was in 2013. Among two types of bacterial infections, 94.44% were of multibacillary and 5.56% were of paucibacillary type. The age range of patients with dapsone ADRs was 11-68 years. The male-to-female ratio was 1.25. The onset of dapsone ADRs after taking MDT was within a minimum of 3 weeks and a maximum of 21 weeks. There were 14 (77.77%) patients who presented with jaundice, 8 (44.44%) with exfoliative dermatitis, 5 (27.77%) with hemolytic anemia and 4 (22.22%) with fever and headache. The rare side effects (5.5%) found were agranulocytosis or toxic epidermal necrolysis. Three patients were cured; some were still on the treatment. Four patients died with dapsone ADRs.</p><p><strong>Conclusion: </strong>The common dapsone ADRs present in leprosy patients were jaundice, exfoliative dermatitis and hemolytic anemia in MDT-treated patients. Patients could be cured by managing the dapsone ADRs effectively on time. Some patients may die of dapsone ADRs if clinicians fail to manage the side effects on time.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"9 ","pages":"73-78"},"PeriodicalIF":2.0,"publicationDate":"2017-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S135846","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35180573","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":"Prediction of efficacy for conversion from adjunctive therapy to monotherapy with eslicarbazepine acetate 800 mg once daily for partial-onset epilepsy.","authors":"Soujanya Sunkaraneni,&nbsp;Julie A Passarell,&nbsp;Elizabeth A Ludwig,&nbsp;Jill Fiedler-Kelly,&nbsp;Janet K Pitner,&nbsp;Todd A Grinnell,&nbsp;David Blum","doi":"10.2147/CPAA.S133815","DOIUrl":"https://doi.org/10.2147/CPAA.S133815","url":null,"abstract":"<p><strong>Purpose: </strong>Eslicarbazepine acetate (ESL) is a once-daily (QD) oral antiepileptic drug (AED) indicated for partial-onset seizures (POS). Clinical studies of gradual conversion to ESL 1,200 and 1,600 mg QD monotherapies were previously conducted in patients with POS who were not well-controlled by 1 or 2 AEDs. This report describes modeling and simulation of plasma eslicarbazepine (primary active metabolite of ESL) concentrations and time to monotherapy study exit to predict efficacy for conversion to ESL monotherapy at a lower dose of 800 mg, as an option for patients requiring or not tolerating higher doses since this regimen is effective in adjunctive therapy for POS.</p><p><strong>Patients and methods: </strong>A previously developed population pharmacokinetic model for ESL monotherapy was used to predict minimum plasma eslicarbazepine concentration (<i>C</i>_min) in 1,500 virtual patients taking 1 (n=1,000) or 2 (n=500) AEDs at baseline, treated with ESL 400 mg QD for 1 week, followed by 800 mg QD for 17 weeks (similar to ESL monotherapy trials where the other AEDs were withdrawn during the first 6 weeks following titration to the randomized ESL dose). Model-predicted <i>C</i>_min as a time-varying covariate and number of baseline AEDs were used to determine the weekly probability of each patient meeting exit criteria (65.3% threshold) indicative of worsening seizure control in 500 simulated ESL monotherapy trials. A previously developed extended Cox proportional hazards exposure-response model was used to relate time-varying eslicarbazepine exposure to the time to study exit.</p><p><strong>Results: </strong>For virtual patients receiving ESL monotherapy (800 mg QD), the 95% upper prediction limit for exit rate at 112 days of 34.9% in patients taking 1 AED at baseline was well below the 65.3% threshold from historical control trials, while the estimate for patients taking 2 AEDs (70.6%) was slightly above the historical control threshold.</p><p><strong>Conclusion: </strong>This model-based assessment supports conversion to ESL 800 mg QD monotherapy for POS in adults taking 1 AED. For patients taking 2 concomitant AEDs, however, prescribers should consider maintenance doses of 1,200 or 1,600 mg ESL QD to reduce the likelihood of seizure worsening if conversion to ESL monotherapy is contemplated.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"9 ","pages":"65-72"},"PeriodicalIF":2.0,"publicationDate":"2017-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S133815","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35180572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An integrated epidemiological and neural net model of the warfarin effect in managed care patients.","authors":"David M Jacobs,&nbsp;Filip Stefanovic,&nbsp;Greg Wilton,&nbsp;Andres Gomez-Caminero,&nbsp;Jerome J Schentag","doi":"10.2147/CPAA.S136243","DOIUrl":"https://doi.org/10.2147/CPAA.S136243","url":null,"abstract":"<p><strong>Introduction: </strong>Risk assessment tools are utilized to estimate the risk for stroke and need of anticoagulation therapy for patients with atrial fibrillation (AF). These risk stratification scores are limited by the information inputted into them and a reliance on time-independent variables. The objective of this study was to develop a time-dependent neural net model to identify AF populations at high risk of poor clinical outcomes and evaluate the discriminatory ability of the model in a managed care population.</p><p><strong>Methods: </strong>We performed a longitudinal, cohort study within a health-maintenance organization from 1997 to 2008. Participants were identified with incident AF irrespective of warfarin status and followed through their duration within the database. Three clinical outcome measures were evaluated including stroke, myocardial infarction, and hemorrhage. A neural net model was developed to identify patients at high risk of clinical events and defined to be an \"enriched\" patient. The model defines the enrichment based on the top 10 minimum mean square error output parameters that describe the three clinical outcomes. Cox proportional hazard models were utilized to evaluate the outcome measures.</p><p><strong>Results: </strong>Among 285 patients, the mean age was 74±12 years with a mean follow-up of 4.3±2.6 years, and 154 (54%) were treated with warfarin. After propensity score adjustment, warfarin use was associated with a slightly increased risk of adverse outcomes (including stroke, myocardial infarction, and hemorrhage), though it did not attain statistical significance (adjusted hazard ratio [aHR] =1.22; 95% confidence interval [CI] 0.75-1.97; <i>p</i>=0.42). Within the neural net model, subjects at high risk of adverse outcomes were identified and labeled as \"enriched.\" Following propensity score adjustment, enriched subjects were associated with an 81% higher risk of adverse outcomes as compared to nonenriched subjects (aHR=1.81; 95% CI, 1.15-2.88; <i>p</i>=0.01).</p><p><strong>Conclusion: </strong>Enrichment methodology improves the statistical discrimination of meaningful endpoints when used in a health records-based analysis.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"9 ","pages":"55-64"},"PeriodicalIF":2.0,"publicationDate":"2017-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S136243","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35053193","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":"Comparative analysis of the safety and tolerability of fixed-dose artesunate/amodiaquine versus artemether/lumefantrine combinations for uncomplicated <i>falciparum</i> malaria in pregnancy: a randomized open label study.","authors":"Osede I Iribhogbe,&nbsp;Igue Emmanuel,&nbsp;Marylove Odianosen","doi":"10.2147/CPAA.S131351","DOIUrl":"https://doi.org/10.2147/CPAA.S131351","url":null,"abstract":"<p><p>A comparative clinical study was conducted to evaluate the safety and tolerability of two commonly used fixed dose artemisinin-based combinations for the treatment of uncomplicated <i>Plasmodium falciparum</i> malaria in the second and third trimester of pregnancy. To achieve this, a total of 155 participants were recruited for the study. Eighty of these were drawn from pregnant women who came for routine antenatal care while 40 nonpregnant participants were recruited from apparently healthy females in the community. Eighty pregnant participants with uncomplicated <i>P. falciparum</i> malaria were randomized into artesunate/amodiaquine (AA) and artemether/lumefantrine (AL) treatment arms while 40 nonpregnant and 35 nonmalarious pregnant women were used as control. The interventional groups received standard fixed dose combinations of AA (100/270 mg) daily or AL (20/120 mg) twice daily for 3 days. Blood samples were collected on day 4 and patients were followed-up closely to ascertain the safety of the drugs. The study showed a significant (<i>p</i><0.0001) elevation of alkaline phosphatase in the AA and AL group compared to the nonpregnant control and a significant (<i>p</i><0.05) elevation of alanine transaminase and aspartate transaminase level in the AL combination group when compared with the AA group. The elevated hepatic enzymes were within the normal range for pregnancy and were not clinically significant. Adverse event rate was higher in the AA group (n=28 [70%]) when compared to the AL group (n=4 [10%]) although the drugs were well-tolerated in both treatment arms. In conclusion, the use of these combinations is safe in the second and third trimester of pregnancy. However, we recommend active pharmacovigilance and spontaneous drug reporting of the agents in order to continuously monitor safety in the vastly heterogeneous population.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"9 ","pages":"45-54"},"PeriodicalIF":2.0,"publicationDate":"2017-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S131351","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35020737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics and outcome of tazobactam/piperacillin in Japanese patients undergoing low-flow continuous renal replacement therapy: dosage considerations.","authors":"Hanako Kohama,&nbsp;Takeshi Ide,&nbsp;Kazuro Ikawa,&nbsp;Norifumi Morikawa,&nbsp;Shinichi Nishi","doi":"10.2147/CPAA.S127502","DOIUrl":"https://doi.org/10.2147/CPAA.S127502","url":null,"abstract":"<p><strong>Background: </strong>Tazobactam/piperacillin (TAZ/PIPC), which is often combined with continuous renal replacement therapy (CRRT), induces renal excretion and is thought to have a high component removal rate for blood purification. CRRT procedures vary depending on the country, region, and institution. It is not clear whether the dose of TAZ/PIPC for use in Japan can be determined based on studies conducted in other countries. Therefore, in this study, we examined the suitability of recommended dose in Japan.</p><p><strong>Methods: </strong>The study subjects consisted of 10 patients who received TAZ/PIPC during CRRT in the intensive care unit of Hyogo College of Medicine, Nishinomiya, Japan. We used a one-compartment model to characterize and parameterize the pharmacokinetics of TAZ/PIPC because their blood levels were eliminated monoexponentially.</p><p><strong>Results: </strong>Compared with the data of healthy adults, the half-lives (t_1/2) of both PIPC and TAZ were prolonged while their clearance rates decreased.</p><p><strong>Conclusion: </strong>For the continuous hemodiafiltration procedure adopted in Japan, we concluded that the dose and frequency were appropriate because the patients who received PIPC/TAZ 2.25 g twice a day during continuous hemodiafiltration maintained appropriate blood levels of both PIPC and TAZ.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"9 ","pages":"39-44"},"PeriodicalIF":2.0,"publicationDate":"2017-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S127502","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34800691","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":"Pharmaceutical characterization of novel tenofovir liposomal formulations for enhanced oral drug delivery: in vitro pharmaceutics and Caco-2 permeability investigations.","authors":"Crystal B Spinks,&nbsp;Ahmed S Zidan,&nbsp;Mansoor A Khan,&nbsp;Muhammad J Habib,&nbsp;Patrick J Faustino","doi":"10.2147/CPAA.S119875","DOIUrl":"https://doi.org/10.2147/CPAA.S119875","url":null,"abstract":"<p><p>Tenofovir, currently marketed as the prodrug tenofovir disoproxil fumarate, is used clinically to treat patients with HIV/AIDS. The oral bioavailability of tenofovir is relatively low, limiting its clinical effectiveness. Encapsulation of tenofovir within modified long-circulating liposomes would deliver this hydrophilic anti-HIV drug to the reticuloendothelial system for better therapeutic efficacy. The objectives of the current study were to prepare and pharmaceutically characterize model liposomal tenofovir formulations in an attempt to improve their bioavailability. The entrapment process was performed using film hydration method, and the formulations were characterized in terms of encapsulation efficiency and Caco-2 permeability. An efficient reverse-phase high-performance liquid chromatography method was developed and validated for tenofovir quantitation in both in vitro liposomal formulations and Caco-2 permeability samples. Separation was achieved isocratically on a Waters Symmetry C8 column using 10 mM Na₂PO₄/acetonitrile pH 7.4 (95:5 v/v). The flow rate was 1 mL/min with a 12 min elution time. Injection volume was 10 µL with ultraviolet detection at 270 nm. The method was validated according to United States Pharmacopeial Convention category I requirements. The obtained result showed that tenofovir encapsulation within the prepared liposomes was dependent on the employed amount of the positive charge-imparting agent. The obtained results indicated that calibration curves were linear with <i>r</i>² > 0.9995 over the analytical range of 1-10 µg/mL. Inter- and intraday accuracy and precision values ranged from 95% to 101% and 0.3% to 2.6%, respectively. The method was determined to be specific and robust. Regarding the potential of the prepared vectors to potentiate tenofovir permeability through the Caco-2 model, a 10-fold increase in tenofovir apparent permeability was observed compared to its oral solution. In conclusion, this novel and validated method was successfully applied to characterize both in vitro encapsulation efficiency and Caco-2 permeability transport for the pharmaceutical assessment of novel tenofovir formulations.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"9 ","pages":"29-38"},"PeriodicalIF":2.0,"publicationDate":"2017-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S119875","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34783859","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}