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Antibiotics (Basel, Switzerland) Apr 2023While the relevance of inter-ethnic differences to the pharmacokinetic variabilities of antimicrobials has been reported in studies recruiting healthy subjects,... (Review)
Review
While the relevance of inter-ethnic differences to the pharmacokinetic variabilities of antimicrobials has been reported in studies recruiting healthy subjects, differences in antimicrobial pharmacokinetics between Asian and non-Asian patients with severe pathologic conditions require further investigation. For the purpose of describing the potential differences in antimicrobial pharmacokinetics between Asian and non-Asian populations, a systematic review was performed using six journal databases and six theses/dissertation databases (PROSPERO record CRD42018090054). The pharmacokinetic data of healthy volunteers and non-critically ill and critically ill patients were reviewed. Thirty studies on meropenem, imipenem, doripenem, linezolid, and vancomycin were included in the final descriptive summaries. In studies recruiting hospitalised patients, inconsistent differences in the volume of distribution (V) and drug clearance (CL) of the studied antimicrobials between Asian and non-Asian patients were observed. Additionally, factors other than ethnicity, such as demographic (e.g., age) or clinical (e.g., sepsis) factors, were suggested to better characterise these pharmacokinetic differences. Inconsistent differences in pharmacokinetic parameters between Asian and non-Asian subjects/patients may suggest that ethnicity is not an important predictor to characterise interindividual pharmacokinetic differences between meropenem, imipenem, doripenem, linezolid, and vancomycin. Therefore, the dosing regimens of these antimicrobials should be adjusted according to patients' demographic or clinical characteristics that can better describe pharmacokinetic differences.
PubMed: 37237706
DOI: 10.3390/antibiotics12050803 -
Clinical Pharmacokinetics Nov 2022An ever-growing body of evidence supports the impact of cytokine modulation on the patient's phenotypic drug response. The aim of this systematic review was to analyze... (Review)
Review
The Cytokine Release Syndrome and/or the Proinflammatory Cytokines as Underlying Mechanisms of Downregulation of Drug Metabolism and Drug Transport: A Systematic Review of the Clinical Pharmacokinetics of Victim Drugs of this Drug-Disease Interaction Under Different Clinical Conditions.
BACKGROUND AND OBJECTIVE
An ever-growing body of evidence supports the impact of cytokine modulation on the patient's phenotypic drug response. The aim of this systematic review was to analyze the clinical studies that assessed the pharmacokinetics of victim drugs of this drug-disease interaction in the presence of different scenarios of cytokine modulation in comparison with baseline conditions.
METHODS
We conducted a systematic review by searching the PubMed-MEDLINE database from inception until February 2022 to retrieve prospective and/or retrospective observational studies, population pharmacokinetic studies, phase I studies, and/or case series/reports that investigated the impact of cytokine modulation on the pharmacokinetic behavior of victim drugs. Only studies providing quantitative pharmacokinetic data of victim drugs by comparing normal status versus clinical conditions with documented cytokine modulation or by assessing the influence of anti-inflammatory biological agents on metabolism and/or transport of victim drugs were included.
RESULTS
Overall, 26 studies were included. Rheumatoid arthritis (6/26; 23.1%) and sepsis (5/26; 19.2%) were the two most frequently investigated pro-inflammatory clinical scenarios. The victim drug most frequently assessed was midazolam (14/26; 53.8%; as a probe for cytochrome P450 [CYP] 3A4). Cytokine modulation showed a moderate inhibitory effect on CYP3A4-mediated metabolism (area under the concentration-time curve increase and/or clearance decrease between 1.98-fold and 2.59-fold) and a weak-to-moderate inhibitory effect on CYP1A2, CYP2C9, and CYP2C19-mediated metabolism (in the area under the concentration-time curve increase or clearance decrease between 1.29-fold and 1.97-fold). Anti-interleukin-6 agents showed remarkable activity in counteracting downregulation of CYP3A4-mediated activity (increase in the area under the concentration-time curve between 1.75-fold and 2.56-fold).
CONCLUSIONS
Cytokine modulation may cause moderate or weak-to-moderate downregulation of metabolism/transport of victim drugs, and this may theoretically have relevant clinical consequences.
Topics: Humans; Cytochrome P-450 CYP3A; Cytokine Release Syndrome; Cytokines; Down-Regulation; Prospective Studies; Retrospective Studies; Drug Interactions
PubMed: 36059001
DOI: 10.1007/s40262-022-01173-8 -
PLoS Neglected Tropical Diseases Oct 2022Albendazole is an orally administered anti-parasitic medication with widespread usage in a variety of both programmatic and clinical contexts. Previous work has shown...
BACKGROUND
Albendazole is an orally administered anti-parasitic medication with widespread usage in a variety of both programmatic and clinical contexts. Previous work has shown that the drug's pharmacologically active metabolite, albendazole sulfoxide, is characterised by substantial inter-individual pharmacokinetic variation. This variation might have implications for the efficacy of albendazole treatment, but current understanding of the factors associated with this variation remains incomplete.
METHODOLOGY/PRINCIPAL FINDINGS
We carried out a systematic review to identify references containing temporally disaggregated data on the plasma concentration of albendazole and/or (its pharmacologically-active metabolite) albendazole sulfoxide following a single oral dose. These data were then integrated into a mathematical modelling framework to infer albendazole sulfoxide pharmacokinetic parameters and relate them to characteristics of the groups being treated. These characteristics included age, weight, sex, dosage, infection status, and whether patients had received a fatty meal prior to treatment or other drugs alongside albendazole. Our results highlight a number of factors systematically associated with albendazole sulfoxide pharmacokinetic variation including age, existing parasitic infection and receipt of a fatty meal. Age was significantly associated with variation in albendazole sulfoxide systemic availability and peak plasma concentration achieved; as well as the clearance rate (related to the half-life) after adjusting for variation in dosage due to differences in body weight between children and adults. Receipt of a fatty meal prior to treatment was associated with increased albendazole sulfoxide systemic availability (and by extension, peak plasma concentration and total albendazole sulfoxide exposure following the dose). Parasitic infection (particularly echinococcosis) was associated with altered pharmacokinetic parameters, with infected populations displaying distinct characteristics to uninfected ones.
CONCLUSIONS/SIGNIFICANCE
These results highlight the extensive inter-individual variation that characterises albendazole sulfoxide pharmacokinetics and provide insight into some of the factors associated with this variation.
Topics: Humans; Adult; Child; Albendazole; Anthelmintics; Echinococcosis; Administration, Oral
PubMed: 36306320
DOI: 10.1371/journal.pntd.0010497 -
Pharmaceutics Feb 2023Rivaroxaban has been widely used to prevent and treat various thromboembolic diseases for more than a decade. However, whether a lower dose of rivaroxaban is required... (Review)
Review
Rivaroxaban has been widely used to prevent and treat various thromboembolic diseases for more than a decade. However, whether a lower dose of rivaroxaban is required for Asians is still debatable. This review aimed to explore the potential ethnic difference in pharmacokinetic/pharmacodynamic (PK/PD) characteristics between Asians and Caucasians. A systematic search was conducted and twenty-four studies were identified, of which 10 were conducted on Asian adults, 11 on predominantly Caucasian adults, and 3 on Caucasian pediatrics. The apparent clearance (CL/F) of rivaroxaban in Caucasian adults with non-valvular atrial fibrillation (6.45-7.64 L/h) was about 31-43% higher than that in Asians (4.46-5.98 L/h) taking 10~20 mg rivaroxaban every 24 h. Moreover, there was no obvious difference in CL/F among Japanese, Chinese, Thai, and Irani people. Regarding PK/PD relationship, prothrombin time was linked to rivaroxaban concentration in a linear or near-linear manner, and Factor Xa activity was linked with the E model. The exposure-response relationship was comparable between Asians and Caucasians. Renal function has a significant influence on CL/F, and no covariate was recognized for exposure-response relationship. In conclusion, a lower dose of rivaroxaban might be required for Asians, and further studies are warranted to verify this ethnic difference to facilitate optimal dosing regimens.
PubMed: 36839909
DOI: 10.3390/pharmaceutics15020588 -
Lipids in Health and Disease Jan 2024Obstructive sleep apnea (OSA) has a bidirectional association with metabolic syndrome, and insulin resistance (IR). The triglyceride-glucose (TyG) index could be a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Obstructive sleep apnea (OSA) has a bidirectional association with metabolic syndrome, and insulin resistance (IR). The triglyceride-glucose (TyG) index could be a simply calculated marker of IR in OSA. However, its clinical application appears still limited. Hence, this systematic review and meta-analysis aimed to respond to this question by analyzing all the existing studies showing an association between OSA and the TyG index.
METHODS
Four online databases, including PubMed, Scopus, the Web of Science, and Embase were searched for studies evaluating the TyG index in OSA. After screening and data extraction, a random-effect meta-analysis was performed to compare the TyG index in OSA patients vs. healthy controls by calculating standardized mean difference (SMD) and 95% confidence interval (CI) and pooling the area under the curves (AUCs) for diagnosis of OSA based on this index.
RESULTS
Ten studies involving 16,726 individuals were included in the current systematic review. Meta-analysis indicated that there was a significantly higher TyG index in patients with OSA, compared with the healthy controls (SMD 0.856, 95% CI 0.579 to 1.132, P < 0.001). Also, TyG had a diagnostic ability for OSA representing a pooled AUC of 0.681 (95% CI 0.627 to 0.735). However, based on the two studies' findings, no difference between different severities of OSA was observed. Finally, our data showed that the TyG index is a good potential predictor of adverse outcomes in these patients.
CONCLUSION
Our study revealed that the TyG index is an easy-to-measure marker of IR for assessing OSA, both in diagnosis and prognosis. Our study supports its implementation in routine practice to help clinicians in decision-making and patient stratification.
Topics: Humans; Area Under Curve; Databases, Factual; Glucose; Insulin Resistance; Sleep Apnea, Obstructive; Triglycerides
PubMed: 38185682
DOI: 10.1186/s12944-024-02005-3 -
Alcoholism, Clinical and Experimental... Feb 2017Decades of alcohol research have established the health risks and pharmacodynamic profile of oral alcohol consumption. Despite isolated periods of public health concern,... (Review)
Review
Decades of alcohol research have established the health risks and pharmacodynamic profile of oral alcohol consumption. Despite isolated periods of public health concern, comparatively less research has evaluated exposure to alcohol vapor. Inhaled alcohol initially bypasses first-pass metabolism and rapidly reaches the arterial circulation and the brain, suggesting that this route of administration may be associated with pharmacological effects that increase the risk of addiction. However, detailed reviews assessing the possible effects of inhaled alcohol in humans are lacking. A comprehensive, systematic literature review was conducted using Google Scholar and PubMed to examine manuscripts studying exposure to inhaled alcohol and measurement of biomarkers (biochemical or functional) associated with alcohol consumption in human participants. Twenty-one publications reported on alcohol inhalation. Fourteen studies examined inhalation of alcohol vapor associated with occupational exposure (e.g., hand sanitizer) in a variety of settings (e.g., naturalistic, laboratory). Six publications measured inhalation of alcohol in a controlled laboratory chamber, and 1 evaluated direct inhalation of an e-cigarette with ethanol-containing "e-liquid." Some studies have reported that inhalation of alcohol vapor results in measurable biomarkers of acute alcohol exposure, most notably ethyl glucuronide. Despite the lack of significantly elevated blood alcohol concentrations, the behavioral consequences and subjective effects associated with repeated use of devices capable of delivering alcohol vapor are yet to be determined. No studies have focused on vulnerable populations, such as adolescents or individuals with alcohol use disorder, who may be most at risk of problems associated with alcohol inhalation.
Topics: Administration, Inhalation; Adolescent; Alcohol Drinking; Animals; Central Nervous System Depressants; Electronic Nicotine Delivery Systems; Ethanol; Humans; Vaping
PubMed: 28054395
DOI: 10.1111/acer.13291 -
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 -
Molecules (Basel, Switzerland) Sep 2017, as a traditional Chinese medicine, has been widely used both as a single herb and in compound prescriptions in Asia, mainly due to its heat-clearing and detoxifying... (Review)
Review
, as a traditional Chinese medicine, has been widely used both as a single herb and in compound prescriptions in Asia, mainly due to its heat-clearing and detoxifying effects. Modern pharmacology has proved possesses various therapeutic effects, both in vitro and in vivo, such as anti-inflammatory, antibacterial and antiviral activities. Up to now, three hundred and twenty-one compounds have been identified and sensitive analytical methods have been established for its quality control. Recently, the pharmacokinetics of and its bioactive compounds have been reported, providing valuable information for its clinical application. Therefore, this systematic review focused on the newest scientific reports on and extensively summarizes its phytochemistry, pharmacology, pharmacokinetics and standardization procedures, especially the difference between the two applied types-unripe and ripe -in the hope of providing a helpful reference and guide for its clinical applications and further studies.
Topics: Anti-Inflammatory Agents; Antineoplastic Agents, Phytogenic; Antioxidants; Antiviral Agents; Drug Discovery; Drugs, Chinese Herbal; Forsythia; Humans; Phytochemicals
PubMed: 28869577
DOI: 10.3390/molecules22091466 -
British Journal of Clinical Pharmacology Jul 2020This is a PROSPERO registered systematic review (CRD42018105207), conducted to summarize the available knowledge regarding the population pharmacokinetics of digoxin in... (Review)
Review
This is a PROSPERO registered systematic review (CRD42018105207), conducted to summarize the available knowledge regarding the population pharmacokinetics of digoxin in paediatrics and to identify the sources of variability in its disposition. PubMed, ISI Web of Science, SCOPUS and Science Direct databases were searched from inception to January 2019. All paediatric population pharmacokinetic studies of digoxin that utilized the nonlinear mixed-effect modelling approach were incorporated in this review, and data were synthesized descriptively. After application of the inclusion-exclusion criteria 8 studies were included. Most studies described digoxin pharmacokinetics as a 1-compartment model with only 1 study describing its pharmacokinetics as 2-compartments. Age was an important predictor of clearance in studies involving neonates or infants, other predictors of clearance were weight, height, serum creatinine, coadministration of spironolactone and presence of congestive heart failure. Congestive heart failure was also associated with an increased volume of distribution in 1 study. The estimated value of apparent clearance in a typical individual standardized by mean weight ranged between 0.24 and 0.56 L/h/kg, the interindividual variability in clearance ranged between 7.0 and 35.1%. Half of the studies evaluated the performance of their developed models via external evaluation. In conclusion, substantial predictors of digoxin pharmacokinetics in the paediatric population in addition to model characteristics and evaluation techniques are presented. For clinicians, clearance could be predicted using age especially in neonates or infants, weight, height, serum creatinine, coadministration of medications and disease status. For future researchers, designing pharmacokinetic studies that allow 2-compartment modelling and linking pharmacokinetics with pharmacodynamics is recommended.
Topics: Child; Digoxin; Heart Failure; Humans; Infant; Infant, Newborn; Models, Biological; Nonlinear Dynamics; Pediatrics; Spironolactone
PubMed: 32153059
DOI: 10.1111/bcp.14272 -
Epilepsia Open Apr 2024Antiseizure medications (ASMs) constitute the principal of treatment for patients with epilepsy, where long-term treatment is usually necessary. The purpose of this... (Review)
Review
Antiseizure medications (ASMs) constitute the principal of treatment for patients with epilepsy, where long-term treatment is usually necessary. The purpose of this systematic review is to provide practical and useful information regarding various aspects of the interactions between ASMs and foods and drinks. MEDLINE and ScienceDirect, from the inception to July 15, 2023, were searched for related publications. In both electronic databases, the following search strategy was applied, and the following keywords were used (in title/abstract): "food OR drink" AND "antiepileptic OR antiseizure." The primary search yielded 738 studies. After implementing our inclusion and exclusion criteria, we could identify 19 studies on the issue of interest for our endeavor. Four studies were identified in the recheck process and not by the primary search. All studies provided low level of evidence. Interactions between foods and ASMs are a common phenomenon. Many factors may play a role for such an interaction to come to play; these include drug properties, administration route, and administration schedule, among others. Drugs-foods (-drinks) interactions may change the drug exposure or plasma levels of drugs (e.g., grapefruit juice increases carbamazepine concentrations and the bioavailability of cannabidiol is increased 4-5 folds with concomitant intake of fat-rich food); this may require dosage adjustments. Interactions between ASMs and foods and drinks may be important. This should be taken seriously into consideration when consulting patients and their caregivers about ASMs. Future well-designed investigations should explore the specific interactions between foods (and drinks) and ASMs to clarify whether they are clinically important. PLAIN LANGUAGE SUMMARY: Interactions between antiseizure medications and foods and drinks may be important. This should be taken into consideration in patients with epilepsy.
Topics: Humans; Anticonvulsants; Biological Availability; Benzodiazepines; Food; Epilepsy
PubMed: 38345419
DOI: 10.1002/epi4.12918