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Current Drug Metabolism 2021Although the pharmacokinetic variability of Tacrolimus (Tac) metabolism is primarily influenced by CYP3A5 genotypes, the potential effect according to CYP3A5... (Meta-Analysis)
Meta-Analysis
Effects of CPY3A5 Genetic Polymorphisms on the Pharmacokinetics of Extendedrelease and Immediate-release Tacrolimus Formulations in Renal Transplant Recipients: A Systematic Review and Meta-analysis.
BACKGROUND
Although the pharmacokinetic variability of Tacrolimus (Tac) metabolism is primarily influenced by CYP3A5 genotypes, the potential effect according to CYP3A5 polymorphisms in Tac extended-release (Tac-ER) and immediate-release (Tac-IR) and between these formulations' conversion needs further investigation. The purpose of this study was to clarify the association of CYP3A5 genotypes and pharmacokinetics of different Tac formulations in renal transplant recipients.
METHODS
PubMed, EMBASE, and Cochrane Library databases were searched for eligible studies (protocol registration No. CRD 42019133790 in PROSPERO network). The summary weighted mean difference with 95% confidence intervals was calculated for pharmacokinetic parameters using the random-effects model according to posttransplantation periods, genotypes and formulations. Sensitivity analysis, publication bias, and subgroup analyses were conducted.
RESULTS
A total of 27 studies involving 2,713 renal transplant recipients were adopted. Whether patients treated with Tac-ER or Tac-IR, CYP3A5 non-expressors (*3/*3) had a decreased daily dose and CL/F, an increased Ctrough, Ctrough/D, AUC0-24h/D and Cmax/D than expressors (*1/*1 or *1/*3) at most post-transplantation periods. Furthermore, when 1:1 dose conversion from Tac-IR to Tac-ER (all at ≥12 months post-transplantation), Ctrough and Cmax were decreased in both CYP3A5 non-expressors and expressors, while daily dose was only decreased in CYP3A5 nonexpressors and AUC0-24h was only decreased in CYP3A5 expressors. Finally, subgroup analyses indicated that ethnicity, mean age, and male percentage influenced daily dose and Ctrough of Tac, especially for Tac-IR.
CONCLUSION
The results indicated that CYP3A5 genotypes affect the pharmacokinetics of Tac in renal transplant recipients in both formulations and between formulations' conversion. Future studies should be exploring more other associations of CYP3A5 genotypes and the pharmacodynamics of Tac.
Topics: Cytochrome P-450 CYP3A; Dosage Forms; Humans; Immunosuppressive Agents; Kidney Transplantation; Pharmacokinetics; Polymorphism, Genetic; Tacrolimus
PubMed: 34525930
DOI: 10.2174/1389200222666210825160021 -
Advances in Nutrition (Bethesda, Md.) Jul 2017Polyols are sugar alcohols found in certain fruits, vegetables, and sugar-free sweeteners. They make up a component of the diet low in fermentable oligosaccharides,... (Review)
Review
Polyols are sugar alcohols found in certain fruits, vegetables, and sugar-free sweeteners. They make up a component of the diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols, which is gaining popularity in the treatment of patients with irritable bowel syndrome (IBS). We conducted a systematic review to evaluate the effects of polyols on the gastrointestinal tract in healthy men and women and in patients with IBS. Utilizing PubMed, Ovid, and Embase databases, we conducted a search on individual polyols and each of these terms: fermentation, absorption, motility, permeability, and gastrointestinal symptoms. Standard protocols for a systematic review were followed. We found a total of 1823 eligible articles, 79 of which were included in the review. Overall, available work has shown that polyol malabsorption generally occurs in a dose-dependent fashion in healthy individuals, and malabsorption increases when polyols are ingested in combination. However, studies in patients with IBS have shown conflicting results pertaining to polyol malabsorption. Polyol ingestion can lead to intestinal dysmotility in patients with IBS. Regarding the microbiome, moderate doses of polyols have been shown to shift the microbiome toward an increase in bifidobacteria in healthy individuals and may therefore be beneficial as prebiotics. However, data are limited regarding polyols and the microbiome in patients with IBS. Polyols can induce dose-dependent symptoms of flatulence, abdominal discomfort, and laxative effects when consumed by both healthy volunteers and patients with IBS. Further research is needed to better understand the effects of specific polyols on gastrointestinal function, sensation, and the microbiome in health and gastrointestinal disorders such as IBS.
Topics: Fruit; Gastrointestinal Absorption; Gastrointestinal Microbiome; Gastrointestinal Tract; Humans; Irritable Bowel Syndrome; Malabsorption Syndromes; Polymers; Randomized Controlled Trials as Topic; Vegetables
PubMed: 28710145
DOI: 10.3945/an.117.015560 -
European Journal of Clinical... Oct 2010protein energy malnutrition (PEM) is a nutritional problem affecting many children world-wide. Its association with a wide spectrum of infections necessitates multiple... (Review)
Review
OBJECTIVE
protein energy malnutrition (PEM) is a nutritional problem affecting many children world-wide. Its association with a wide spectrum of infections necessitates multiple drug therapies. A systematic review was performed to determine the effects of PEM on drug pharmacokinetics.
METHODS
literature searches in the MEDLINE and EMBASE databases (January 1960 to December 2009) were performed. Malnutrition, undernutrition, underweight, protein-energy malnutrition, protein-calorie malnutrition, marasmus, marasmic-kwashiorkor or kwashiorkor was the medical subject heading (MeSH) descriptor used. Inclusion criteria were abstracts that assessed or discussed absorption, distribution, metabolism, elimination, clearance, pharmacokinetics or pharmacodynamics of drugs, except micronutrients and appetite-stimulating drugs.
RESULTS
altogether, 41 publications were identified. A total of 34 drugs were studied. The absorption of 18 drugs was studied; the extent of absorption (AUC) was unaffected for 10 drugs. The plasma protein binding of 20 drugs was evaluated; it was significantly reduced for 12 drugs. The volume of distribution (Vd) of 13 drugs was evaluated; it was, however, unaffected for most of the drugs. The effect of PEM on total clearance and the half-life of drugs primarily metabolised by the liver was studied for 8 drugs. There was decreased total clearance and an associated increased half-life of 5 drugs. For 2 drugs (chloramphenicol and quinine), different degrees of PEM affected total clearance differently. The total clearance of six drugs primarily eliminated by the kidneys was studied; it was unaffected for four drugs, but significantly decreased for two drugs (cefoxitin and penicillin).
CONCLUSIONS
considering the proportion of children affected with PEM world-wide, there have been relatively few pharmacokinetic studies of drugs frequently used for their treatment. More studies are therefore required to establish the appropriate dose and safety of these drugs for PEM children. The studies need to recognise that PEM is a disease spectrum and should further look at the differential effects of kwashiorkor and marasmus on drug pharmacokinetics in children.
Topics: Adolescent; Child; Child, Preschool; Half-Life; Humans; Infant; Kwashiorkor; Liver; Pharmacokinetics; Protein-Energy Malnutrition
PubMed: 20552179
DOI: 10.1007/s00228-010-0851-0 -
Clinical Therapeutics Sep 2001Fluticasone propionate is an established corticosteroid administered intranasally for the treatment of rhinitis or by oral inhalation for the treatment of asthma.... (Review)
Review
BACKGROUND
Fluticasone propionate is an established corticosteroid administered intranasally for the treatment of rhinitis or by oral inhalation for the treatment of asthma. Mometasone furoate, a closely related corticosteroid currently available in an intranasal formulation, is being investigated in an oral inhalation formulation for the treatment of asthma.
OBJECTIVE
This article reviews available data on the comparative structure-activity relationships, chemistry, pharmacology, pharmacokinetics, and systemic bioavailability of fluticasone propionate and mometasone furoate to assess whether claims of differences in the absolute systemic bioavailability of the 2 compounds are supported by the published literature.
METHODS
Information for this review was identified through a MEDLINE search of the literature from 1966 to the present that contained the term mometasone or fluticasone. The resulting list was narrowed by excluding articles dealing with dermatologic applications. A systematic review was conducted of the identified literature pertaining to the molecular structure, topical potency, lipophilicity, pharmacokinetics, and bioavailability of the 2 agents. Additionally, the pharmacology of the 2 moieties was assessed by a review of the available literature on receptor binding affinity, transactivation and transrepression potency, and inhibition of inflammatory-cell cytokine expression.
RESULTS
Based on the available data, fluticasone propionate and mometasone furoate have similar physicochemical properties and structure-activity relationships. When administered intranasally, mometasone furoate is reported to have comparable relative systemic bioavailability to that of fluticasone propionate (mean plasma area under the curve, 123 pmol x h/L vs 112 pmol x h/L, respectively). When administered as a single dose by dry powder inhaler, orally inhaled fluticasone propionate is reported to have a total systemic bioavailability of approximately 17%, whereas that of mometasone furoate is reported to be < 1%. However, the mometasone furoate bioavailability study that reported the latter value used lower drug doses and a less sensitive assay than the fluticasone propionate bioavailability study. When multiple-dose data were used, mometasone furoate had an estimated 11% systemic bioavailability, similar to that of fluticasone propionate.
CONCLUSIONS
Inhaled fluticasone propionate and mometasone furoate appear to have comparable potential systemic absorption and, based on the total systemic bioavailabilities of the parent compounds, have a low potential for systemic side effects at the recommended clinical doses. However, in the case of mometasone furoate, the contribution of the active metabolites to systemic effects has not been adequately assessed.
Topics: Administration, Intranasal; Androstadienes; Biological Availability; Cytokines; Fluticasone; Humans; Mometasone Furoate; Pregnadienediols; Receptors, Glucocorticoid; Rhinitis, Allergic, Perennial; Time Factors
PubMed: 11589253
DOI: 10.1016/s0149-2918(01)80113-2 -
European Journal of Clinical... May 2021Ketamine has rapid-onset antidepressant effects in patients with treatment-resistant depression. Common side effects include dissociation (a sense of detachment from...
PURPOSE
Ketamine has rapid-onset antidepressant effects in patients with treatment-resistant depression. Common side effects include dissociation (a sense of detachment from reality) and increases in systolic and diastolic blood pressure. The objective of this structured review was to examine the effect of ketamine formulation and route of administration on its pharmacokinetics, safety and tolerability, to identify formulation characteristics and routes of administration that might minimise side effects.
METHODS
This was a structured review of published ketamine pharmacokinetics, safety and tolerability data for any ketamine formulation. The ratio of ketamine:norketamine was calculated from reported C values, as a measure of first pass metabolism. The effect of formulation and route of administration on safety was evaluated by measuring mean changes in systolic blood pressure and tolerability by changes in dissociation ratings. Data were correlated using Spearman's method.
RESULTS
A total of 41 treatment arms were identified from 21 publications, and included formulation development studies in healthy volunteers, and studies in clinical populations (patients undergoing anaesthesia, or being treated for pain or depression). Ketamine:norketamine ratios were strongly positively correlated with change in dissociation ratings (r = 0.89) and change in blood pressure (r = 0.96), and strongly negatively correlated with ketamine T (r = - 0.87; p < 0.00001 for all). Ketamine T strongly positively correlated with a change in dissociation ratings (r = - 0.96) and change in blood pressure (r = - 0.99; p < 0.00001 for all).
CONCLUSION
Ketamine formulations that maximize first pass metabolism and delay T will be better tolerated and safer than formulations which lack those characteristics.
Topics: Antidepressive Agents; Dissociative Disorders; Drug Administration Routes; Drug Delivery Systems; Humans; Hypertension; Ketamine; Metabolic Clearance Rate
PubMed: 33210159
DOI: 10.1007/s00228-020-03047-z -
Korean Journal of Radiology 2015Meta-analysis of diagnostic test accuracy studies differs from the usual meta-analysis of therapeutic/interventional studies in that, it is required to simultaneously... (Meta-Analysis)
Meta-Analysis Review
Systematic Review and Meta-Analysis of Studies Evaluating Diagnostic Test Accuracy: A Practical Review for Clinical Researchers-Part II. Statistical Methods of Meta-Analysis.
Meta-analysis of diagnostic test accuracy studies differs from the usual meta-analysis of therapeutic/interventional studies in that, it is required to simultaneously analyze a pair of two outcome measures such as sensitivity and specificity, instead of a single outcome. Since sensitivity and specificity are generally inversely correlated and could be affected by a threshold effect, more sophisticated statistical methods are required for the meta-analysis of diagnostic test accuracy. Hierarchical models including the bivariate model and the hierarchical summary receiver operating characteristic model are increasingly being accepted as standard methods for meta-analysis of diagnostic test accuracy studies. We provide a conceptual review of statistical methods currently used and recommended for meta-analysis of diagnostic test accuracy studies. This article could serve as a methodological reference for those who perform systematic review and meta-analysis of diagnostic test accuracy studies.
Topics: Area Under Curve; Databases, Factual; Diagnostic Tests, Routine; Humans; ROC Curve; Research; Software
PubMed: 26576107
DOI: 10.3348/kjr.2015.16.6.1188 -
Therapeutic Drug Monitoring Jun 2022The objective of the present study was to determine the impact of proton pump inhibitors (PPIs) on the pharmacokinetics and pharmacodynamics of mycophenolic acid (MPA). (Meta-Analysis)
Meta-Analysis
PURPOSE
The objective of the present study was to determine the impact of proton pump inhibitors (PPIs) on the pharmacokinetics and pharmacodynamics of mycophenolic acid (MPA).
METHODS
PubMed, Embase, Web of Sciences, and Scopus were systematically searched to identify relevant studies reporting pharmacokinetic parameters [including trough concentration (C0), maximum concentration (Cmax), time to maximum concentration (Tmax), the dose-adjusted area under the concentration-time curve from time 0-12 hours (AUC0-12 h/D), and half-life (t1/2)], and pharmacodynamic outcomes of MPA (eg, acute graft rejection and adverse drug reactions), with and without PPI administration. Pooled effect estimates were calculated using a random-effects model.
RESULTS
Twelve studies involving 473 participants were eligible for inclusion, 11 of which were included in the meta-analysis. PPI exposure was significantly associated with lower C0 [mean difference (MD) = -0.62 mg/L; P = 0.003] lower Cmax (MD = -4.71 mg/L; P = 0.01), and longer Tmax (MD = 0.30 hours; P = 0.0001) of MPA. However, no significant association was observed between PPI exposure and AUC0-12 h/D, t1/2, or any pharmacodynamic outcomes. Based on subgroup analysis, it can be suggested that a significant association between PPI exposure and altered MPA pharmacokinetics was mainly associated with mycophenolate mofetil but not enteric-coated mycophenolate sodium.
CONCLUSIONS
Coadministration of PPIs and mycophenolate mofetil significantly altered the pharmacokinetics of MPA, particularly by decreasing MPA absorption. However, PPI-MPA interactions did not impact pharmacodynamic outcomes of MPA.
Topics: Area Under Curve; Drug Interactions; Graft Rejection; Humans; Immunosuppressive Agents; Mycophenolic Acid; Proton Pump Inhibitors
PubMed: 35239287
DOI: 10.1097/FTD.0000000000000947 -
Journal of Psychiatric Research Jan 2023Currently, depression is diagnosed on the basis of neuropsychological examinations and clinical symptoms, and there is no objective diagnostic method. Several studies... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Currently, depression is diagnosed on the basis of neuropsychological examinations and clinical symptoms, and there is no objective diagnostic method. Several studies have explored the application of microRNAs as potential biomarkers diagnostic for depression. This study aims to determine the diagnostic value of microRNAs for depression.
METHODS
PubMed, Embase, the Cochrane Library, the Web of Science, Wanfang Database, SINOMED, China Science and Technology Journal Databaseand China National Knowledge Infrastructure were searched up to 11 January 2022. Stata (version 16.0) and RevMan (version 5.3) software were used for meta-analysis. The pooled sensitivity, pooled specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio (DOR) were calculated; the summary receiver operating characteristic (SROC) curve was plotted, and the area under the curve (AUC) was calculated. Moreover, meta-regression analyses were performed to determine the source of heterogeneity. Deeks' funnel plot test was used to assess publication bias.
RESULTS
In total, 677 patients were enrolled, including 364 patients with depression and 313 healthy controls. Meta-analysis results showed that the pooled sensitivity, specificity, and DOR of microRNAs for the diagnosis of depression were 0.82 [95% confidence intervals(CI): 0.76, 0.87], 0.70 (95% CI: 0.62, 0.77), and 11 (95% CI: 6, 20), respectively, and the AUC of the SROC was 0.84 (95% CI: 0.80, 0.87).
CONCLUSIONS
MicroRNAs have high sensitivity and specificity in diagnosing depression and are potential diagnostic biomarkers for depression.
REGISTRATION NUMBER
PROSPERO CRD42022303616.
Topics: Humans; MicroRNAs; Depression; ROC Curve; Biomarkers; Area Under Curve; Sensitivity and Specificity
PubMed: 36463628
DOI: 10.1016/j.jpsychires.2022.11.028 -
Fitoterapia Nov 2020Ursolic acid (UA) is a natural pentacyclic triterpenoid compound existing in various traditional Chinese medicinal herbs, and it possesses diverse pharmacological...
Ursolic acid (UA) is a natural pentacyclic triterpenoid compound existing in various traditional Chinese medicinal herbs, and it possesses diverse pharmacological actions and some undesirable adverse effects, even toxicological activities. Due to UA's low solubility and poor bioavailability, and its interaction with gut microbiota after oral administration, the pharmacokinetics of UA remain elusive, leading to obscurity in the pharmacokinetics-pharmacodynamics (PK-PD) profile and relationship for UA. Based on literatures from PubMed, Google Scholar, ResearchGate, Web of Science and Wiley Online Library, with keywords of "pharmacology", "toxicology", "pharmacokinetics", "PK-PD" and "ursolic acid", herein we systematically review the pharmacology and toxicity of UA, and rethink on its pharmacokinetics on the basis of PK-PD model, and seek to delineate the underlying mechanisms for the characteristics of pharmacology and toxicology of UA, and for the pharmacokinetic features of UA particularly from the organ tropism and the interactions between UA and gut microbiota, and lay a solid foundation for development of UA-derived therapeutic agents in clinical settings.
Topics: Animals; Anti-Infective Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiviral Agents; Biological Availability; Cardiovascular Agents; Humans; Solubility; Triterpenes; Ursolic Acid
PubMed: 33010369
DOI: 10.1016/j.fitote.2020.104735 -
The Aging Male : the Official Journal... Dec 2023This study aimed to determine whether the C-reactive protein-to-albumin ratio (CAR) can serve as a prognostic marker in patients with sepsis. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study aimed to determine whether the C-reactive protein-to-albumin ratio (CAR) can serve as a prognostic marker in patients with sepsis.
METHODS
Chinese and English databases were searched to retrieve the included literature. The pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) of the summary receiver operating characteristic (SROC) with their 95% confidence interval (CI) were calculated using the bivariate model. Moreover, the hazard ratio (HR) and 95% CI were calculated using the random effect model.
RESULTS
Nine articles comprising 3224 patients with sepsis were included in the meta-analysis. The pooled SEN was 0.73 (95% CI 0.65-0.80), the pooled SPE was 0.78 (95% CI 0.69-0.84), the pooled PLR was 3.29 (95% CI 2.15-5.03), the pooled NLR was 0.35 (95% CI 0.24-0.49), and the pooled DOR was 9.50 (95% CI 4.38-20.59). The AUC under the SROC was 0.82 (95% CI 0.78-0.85) for the prognostic meta-analysis. The pooled HR was 1.10 (95% CI 1.02-1.18).
CONCLUSIONS
This meta-analysis suggests that a high CAR level is associated with increased mortality and a poor prognosis.
Topics: Humans; C-Reactive Protein; Prognosis; Albumins; Sepsis; Area Under Curve
PubMed: 37752726
DOI: 10.1080/13685538.2023.2261540