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BioMed Research International 2020Clozapine is a second-generation antipsychotic drug that is considered the most effective treatment for refractory schizophrenia. Several clozapine population...
BACKGROUND AND OBJECTIVE
Clozapine is a second-generation antipsychotic drug that is considered the most effective treatment for refractory schizophrenia. Several clozapine population pharmacokinetic models have been introduced in the last decades. Thus, a systematic review was performed (i) to compare published pharmacokinetics models and (ii) to summarize and explore identified covariates influencing the clozapine pharmacokinetics models.
METHODS
A search of publications for population pharmacokinetic analyses of clozapine either in healthy volunteers or patients from inception to April 2019 was conducted in PubMed and SCOPUS databases. Reviews, methodology articles, in vitro and animal studies, and noncompartmental analysis were excluded.
RESULTS
Twelve studies were included in this review. Clozapine pharmacokinetics was described as one-compartment with first-order absorption and elimination in most of the studies. Significant interindividual variations of clozapine pharmacokinetic parameters were found in most of the included studies. Age, sex, smoking status, and cytochrome P450 1A2 were found to be the most common identified covariates affecting these parameters. External validation was only performed in one study to determine the predictive performance of the models.
CONCLUSIONS
Large pharmacokinetic variability remains despite the inclusion of several covariates. This can be improved by including other potential factors such as genetic polymorphisms, metabolic factors, and significant drug-drug interactions in a well-designed population pharmacokinetic model in the future, taking into account the incorporation of larger sample size and more stringent sampling strategy. External validation should also be performed to the previously published models to compare their predictive performances.
Topics: Adult; Antipsychotic Agents; Clozapine; Cytochrome P-450 CYP1A2; Female; Humans; Male; Middle Aged; Models, Biological; Schizophrenia
PubMed: 31998804
DOI: 10.1155/2020/9872936 -
Expert Review of Clinical Pharmacology Jul 2021Oxcarbazepine is commonly used as first-line treatment for partial and generalized tonic-clonic seizures. Owing to the high pharmacokinetic variability, several...
INTRODUCTION
Oxcarbazepine is commonly used as first-line treatment for partial and generalized tonic-clonic seizures. Owing to the high pharmacokinetic variability, several population pharmacokinetic models have been developed for oxcarbazepine to explore potential covariates that affect its pharmacokinetic variation.
AREAS COVERED
This review summarizes the published population pharmacokinetic studies of oxcarbazepine in children and adults available in PubMed and Embase databases. The quality of the retrieved studies was evaluated, and significant covariates that may have an impact on the dosage regimen of oxcarbazepine were explored.
EXPERT OPINION
The pharmacokinetics of oxcarbazepine was founded to be affected by body weight and co-administration with enzyme inducers. Pediatric patients require a higher dose per kilogram than adults because children generally have a higher clearance than adults. Moreover, to maintain the target concentration, patients co-administrate with enzyme inducers need a higher dose than monotherapy due to higher clearance in those patients. Because limited information is available for exposure-response relationship, additional pharmacokinetic/pharmacodynamics investigations of oxcarbazepine need to be conducted to optimize the dosage regimen in clinical practice.
Topics: Adult; Age Factors; Anticonvulsants; Child; Dose-Response Relationship, Drug; Epilepsy; Humans; Models, Biological; Oxcarbazepine
PubMed: 33851561
DOI: 10.1080/17512433.2021.1917377 -
Expert Review of Clinical Pharmacology Jun 2018This article includes a combined analysis of therapeutic drug monitoring (TDM) studies and a review of the marketer's data on pharmacological mechanisms. Areas covered:... (Review)
Review
This article includes a combined analysis of therapeutic drug monitoring (TDM) studies and a review of the marketer's data on pharmacological mechanisms. Areas covered: An article search led to the inclusion of 21 paliperidone studies in the systematic review plus 2 case reports. Paliperidone clearance was calculated from: 1) steady-state studies using concentration/dose (C/D) ratios, and 2) single-dose studies describing 24-h area under the curve calculations. The marketed extended-release formulation has 28% bioavailability. Calculated mean C/D ratios (ng/ml/mg/d) were: 1) 4.09 in 6 studies of 221 non-Korean and non-geriatric adult patients, 2) 2.59 in 2 studies of 100 Korean adult patients, and 3) 6.89 in 1 study with 15 elderly Japanese patients. The limited drug-drug interaction studies indicated that carbamazepine is a clinically relevant inducer requiring three times the dosage, and that valproate, probably an inhibitor, requires half the dosage. Renal impairment markedly decreased paliperidone elimination, and other antipsychotics should be considered. Expert Commentary: We recommend more use of: 1) paliperidone TDM in clinical practice, 2) TDM when moving from oral to long-acting paliperidone, 3) better designs for paliperidone TDM studies, 4) laboratory studies on paliperidone pharmacokinetic mechanisms, and 5) TDM studies comparing paliperidone and risperidone dosing.
Topics: Administration, Oral; Adult; Aged; Antipsychotic Agents; Area Under Curve; Biological Availability; Delayed-Action Preparations; Drug Interactions; Drug Monitoring; Humans; Paliperidone Palmitate; Risperidone
PubMed: 29776316
DOI: 10.1080/17512433.2018.1478727 -
PloS One 2013Cachexia is a weight-loss process caused by an underlying chronic disease such as cancer, chronic heart failure, chronic obstructive pulmonary disease, or rheumatoid... (Review)
Review
Cachexia is a weight-loss process caused by an underlying chronic disease such as cancer, chronic heart failure, chronic obstructive pulmonary disease, or rheumatoid arthritis. It leads to changes in body structure and function that may influence the pharmacokinetics of drugs. Changes in gut function and decreased subcutaneous tissue may influence the absorption of orally and transdermally applied drugs. Altered body composition and plasma protein concentration may affect drug distribution. Changes in the expression and function of metabolic enzymes could influence the metabolism of drugs, and their renal excretion could be affected by possible reduction in kidney function. Because no general guidelines exist for drug dose adjustments in cachectic patients, we conducted a systematic search to identify articles that investigated the pharmacokinetics of drugs in cachectic patients.
Topics: Body Composition; Cachexia; Drug Dosage Calculations; Humans; Pharmacokinetics; Tissue Distribution
PubMed: 24282510
DOI: 10.1371/journal.pone.0079603 -
Pharmacological Reports : PR Apr 2016The number of newly approved generic psychotropic drugs increases every year and, in many countries, their sales exceed the sales of brand-name counterparts. In order... (Review)
Review
The number of newly approved generic psychotropic drugs increases every year and, in many countries, their sales exceed the sales of brand-name counterparts. In order for any generic drug to receive an approval of regulatory authorities, its bioequivalence with the corresponding reference product must be demonstrated. Moreover, generic drugs must meet the same quality standards as reference drugs. However, many psychiatrists express concerns about use of generic drugs. We carried out a systematic analysis of the relevant literature indexed in PubMed and Cochrane databases. The MeSH term "generic" was combined with terms describing antipsychotic and antidepressive drugs, including their pharmaceutical names and relevant mental disorders. All 26 articles including either clinical studies or case reports have been qualified for a detailed analysis. No cases describing switches between two generics were found. Therapeutic equivalence studies evaluating antipsychotics included clozapine, olanzapine, and risperidone. The clinical status was judged to have worsened in 15.7% patients treated with clozapine. The number of relapses before and after the switch was not significantly different in patients treated with olanzapine. Two case reports showed clinical state deterioration after switch to generic risperidone. The clinical outcome after conversion to a generic antidepressant was evaluated only in one retrospective study. That study analyzed the outcomes of treatment with citalopram and revealed mental state deterioration in 11.6% of patients. Only single reports describe cases of impaired efficacy or adverse events after the switch to a generic antidepressant, including fluoxetine, mirtazapine, and venlafaxine. No cases of suicidal attempt after the switch were reported. Although the overall number of described cases is rather modest, health professionals should be aware of possible changes in the therapeutic effectiveness after changing to a generic medicine.
Topics: Antidepressive Agents; Antipsychotic Agents; Clinical Studies as Topic; Drugs, Generic; Humans; Retrospective Studies; Therapeutic Equivalency
PubMed: 26922520
DOI: 10.1016/j.pharep.2015.08.017 -
Drug Research Apr 2016Melatonin is traditionally administered orally but has a poor and variable bioavailability. This study aims to present an overview of studies investigating the... (Review)
Review
BACKGROUND
Melatonin is traditionally administered orally but has a poor and variable bioavailability. This study aims to present an overview of studies investigating the pharmacokinetics of alternative administration routes of melatonin.
METHODS
A systematic literature search was performed and included experimental or clinical studies, investigating pharmacokinetics of alternative administration routes of melatonin in vivo. Alternative administration routes were defined as all administration routes except oral and intravenous.
RESULTS
10 studies were included in the review. Intranasal administration exhibited a quick absorption rate and high bioavailability. Transdermal administration displayed a variable absorption rate and possible deposition of melatonin in the skin. Oral transmucosal administration of melatonin exhibited a high plasma concentration compared to oral administration. Subcutaneous injection of melatonin displayed a rapid absorption rate compared to oral administration.
CONCLUSION
Intranasal administration of melatonin has a large potential, and more research in humans is warranted. Transdermal application of melatonin has a possible use in a local application, due to slow absorption and deposition in the skin. Oral transmucosal administration may potentially be a clinically relevant due to avoiding first-pass metabolism. Subcutaneous injection of melatonin did not document any advantages compared to other administration routes.
Topics: Administration, Cutaneous; Administration, Intranasal; Administration, Mucosal; Administration, Oral; Animals; Biological Availability; Humans; Injections, Subcutaneous; Melatonin
PubMed: 26514093
DOI: 10.1055/s-0035-1565083 -
European Journal of Clinical... Dec 2022Pancreatic cancer is considered one of the most deadly malignancies, primarily because of its diagnostic challenges. We performed a systematic review and diagnostic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pancreatic cancer is considered one of the most deadly malignancies, primarily because of its diagnostic challenges. We performed a systematic review and diagnostic meta-analysis to evaluate the diagnostic value of noncoding salivary RNAs in pancreatic cancer diagnosis.
METHODS
Our investigation involved pertinent studies published in PubMed, Scopus, Web of Science, LIVIVO, Ovid and also the Google Scholar search engine. Specificity and sensitivity were calculated, as were positive and negative likelihood ratios (PLR and NLR), and the diagnostic odds ratio (DOR). The summary receiver-operating characteristics and area under the curve were plotted and assessed.
RESULTS
This meta-analysis and systematic review involved and examined five studies that contained 145 study units with a total of 2731 subjects (1465 pancreatic cancer patients versus 1266 noncancer controls). The pooled specificity, sensitivity, NLR, PLR and DOR were 0.783 (95% CI: 0.759-0.805), 0.829 (95% CI: 0.809-0.848), 0.309 (95% CI: 0.279-0.343), 3.386 (95% CI: 2.956-3.879) and 18.403 (95% CI: 14.753-22.954), respectively, with the area under the curve (AUC) equal to 0.882. Subgroup analyses were conducted based on the saliva type (unstimulated and stimulated), mean age of patients, sample size, type of control, serum carbohydrate antigen 19-9 (CA19-9) level and type of salivary noncoding RNA (microRNA (miRNA) and long noncoding RNA (lncRNA)).
CONCLUSIONS
The results of our systematic review and meta-analysis suggest that noncoding RNA biomarkers in the stimulated saliva could be a promising approach for accurate pancreatic cancer diagnosis in the early stages.
Topics: Humans; Pancreatic Neoplasms; ROC Curve; MicroRNAs; Area Under Curve
PubMed: 35906804
DOI: 10.1111/eci.13848 -
High Altitude Medicine & Biology Jun 2018Bailey, Damian Miles, Benjamin S. Stacey, and Mark Gumbleton. A systematic review and meta-analysis reveals altered drug pharmacokinetics in humans during acute exposure... (Meta-Analysis)
Meta-Analysis
A Systematic Review and Meta-Analysis Reveals Altered Drug Pharmacokinetics in Humans During Acute Exposure to Terrestrial High Altitude-Clinical Justification for Dose Adjustment?
UNLABELLED
Bailey, Damian Miles, Benjamin S. Stacey, and Mark Gumbleton. A systematic review and meta-analysis reveals altered drug pharmacokinetics in humans during acute exposure to terrestrial high altitude-clinical justification for dose adjustment? High Alt Med Biol. 19:141-148, 2018.
OBJECTIVE
While physiological responses during acute ascent to terrestrial high altitude (HA) have the potential to alter the pharmacokinetics (PKs) that define absorption and disposition of medicinal drugs, there have been no systematic reviews and meta-analyses performed to date.
METHODS
We conducted a systematic literature search in June 2017 using NCBI PubMed, EMBASE, Web of Science, and Ovid MEDLINE databases to identify relevant observational studies. Studies were deemed eligible based on the following criteria: (1) participants: healthy, nonacclimatized male or female lowlanders (born and bred at sea level) and (2) environment: exposure to low altitude (LA, ≤600 m), followed by terrestrial high altitude (HA, ≤24 hours to ≥2500 m), the time course specifically selected to avoid interpretive complications associated with erythrocytosis. All PK parameters were standardized to be in the same units and the weighted standardized mean difference (SMD) calculated using a combination of fixed and random effects models with heterogeneity evaluated using χ and I statistics.
RESULTS
Of 20,840 studies reviewed, 6 prospective cohort studies (n = 75) qualified for inclusion, with participants exposed to a mean altitude of 4025 (mean) ± 380 (SD) m. We observed increases for absorption half-life (SMD: 0.40, 95% CI: 0.01-0.80, p = 0.04], elimination half-life (SMD: 0.89, 95% CI: 0.30-1.48, p = 0.003), and erythrocyte binding (SMD: 0.52, 95% CI: 0.16-0.88, p = 0.004) and reduction in clearance (SMD: -0.56, 95% CI: -1.13 to 0.00, p = 0.05).
CONCLUSIONS
Collectively, these findings reveal impairments in both oral absorption and corresponding clearance of the, although limited, sample of drugs at HA that may potentially require closer patient monitoring and dose adjustments to maintain therapeutic efficacy and avoid incidental toxicity.
Topics: Absorption, Physiological; Acclimatization; Adult; Altitude; Erythrocytes; Female; Half-Life; Humans; Male; Metabolic Clearance Rate; Middle Aged; Pharmacokinetics; Prospective Studies
PubMed: 29620950
DOI: 10.1089/ham.2017.0121 -
Food & Function Jan 2023Anthocyanins have multiple health benefits. However, they are prone to degradation during gastrointestinal digestion, impeding their utilization. Various encapsulation... (Meta-Analysis)
Meta-Analysis Review
Anthocyanins have multiple health benefits. However, they are prone to degradation during gastrointestinal digestion, impeding their utilization. Various encapsulation systems have been proposed to improve their bioaccessibility and bioavailability. This review aims to provide a systematic evaluation and meta-analysis of published studies examining the effect of microencapsulation on the bioaccessibility of anthocyanins. A comprehensive and systematic literature search of three databases (Scopus, PubMed, and Web of Science) was conducted. Studies were selected according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria and were reviewed independently by two investigators. Overall, 34 articles were included in the systematic review and 24 were included in the meta-analysis. The fold changes in bioaccessibility between encapsulated and non-encapsulated anthocyanins from eligible studies were calculated. The median and 95% confidence intervals (CI) of the fold changes for spray-drying (median 1.23, 95% CI 0.91-1.92), freeze-drying (median 1.19, 95% CI 0.61-1.28), simple coacervation (median 1.80, 95% CI 1.41-3.20), and complex coacervation (median 1.61, 95% CI 0.21-25.00) were calculated. Simple coacervation showed a promising protection against degradation during digestion. However, when a large number of anthocyanins cannot be released from the microparticles during digestion, encapsulation impedes the bioaccessibility of anthocyanins.
Topics: Anthocyanins; Biological Availability; Freeze Drying
PubMed: 36594512
DOI: 10.1039/d2fo01997c -
Journal of Medical Virology Sep 2023Accurate early detection of the human papillomavirus (HPV) status in head and neck cancer (HNC) is crucial to identify at-risk populations, stratify patients,... (Meta-Analysis)
Meta-Analysis
Accurate early detection of the human papillomavirus (HPV) status in head and neck cancer (HNC) is crucial to identify at-risk populations, stratify patients, personalized treatment options, and predict prognosis. Artificial intelligence (AI) is an emerging tool to dissect imaging features. This systematic review and meta-analysis aimed to evaluate the performance of AI to predict the HPV positivity through the HPV-associated diseased images in HNC patients. A systematic literature search was conducted in databases including Ovid-MEDLINE, Embase, and Web of Science Core Collection for studies continuously published from inception up to October 30, 2022. Search strategies included keywords such as "artificial intelligence," "head and neck cancer," "HPV," and "sensitivity & specificity." Duplicates, articles without HPV predictions, letters, scientific reports, conference abstracts, or reviews were excluded. Binary diagnostic data were then extracted to generate contingency tables and then used to calculate the pooled sensitivity (SE), specificity (SP), area under the curve (AUC), and their 95% confidence interval (CI). A random-effects model was used for meta-analysis, four subgroup analyses were further explored. Totally, 22 original studies were included in the systematic review, 15 of which were eligible to generate 33 contingency tables for meta-analysis. The pooled SE and SP for all studies were 79% (95% CI: 75-82%) and 74% (95% CI: 69-78%) respectively, with an AUC of 0.83 (95% CI: 0.79-0.86). When only selecting one contingency table with the highest accuracy from each study, our analysis revealed a pooled SE of 79% (95% CI: 75-83%), SP of 75% (95% CI: 69-79%), and an AUC of 0.84 (95% CI: 0.81-0.87). The respective heterogeneities were moderate (I for SE and SP were 51.70% and 51.01%) and only low (35.99% and 21.44%). This evidence-based study showed an acceptable and promising performance for AI algorithms to predict HPV status in HNC but was not comparable to the routine p16 immunohistochemistry. The exploitation and optimization of AI algorithms warrant further research. Compared with previous studies, future studies anticipate to make progress in the selection of databases, improvement of international reporting guidelines, and application of high-quality deep learning algorithms.
Topics: Humans; Artificial Intelligence; Papillomavirus Infections; Algorithms; Area Under Curve; Head and Neck Neoplasms; Human Papillomavirus Viruses
PubMed: 37691329
DOI: 10.1002/jmv.29080