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Clinical and Translational Science Apr 2024N-acetyltransferase 2 (NAT2) genetic polymorphisms might alter isoniazid metabolism leading to toxicity. We reviewed the impact of NAT2 genotype status on the... (Review)
Review
N-acetyltransferase 2 (NAT2) genetic polymorphisms might alter isoniazid metabolism leading to toxicity. We reviewed the impact of NAT2 genotype status on the pharmacokinetics, efficacy, and safety of isoniazid, a treatment for tuberculosis (TB). A systematic search for research articles published in Scopus, PubMed, and Embase until August 31, 2023, was conducted without filters or limits on the following search terms and Boolean operators: "isoniazid" AND "NAT2." Studies were selected if NAT2 phenotypes with pharmacokinetics or efficacy or safety of isoniazid in patients with TB were reported. Patient characteristics, NAT2 status, isoniazid pharmacokinetic parameters, early treatment failure, and the prevalence of drug-induced liver injury were extracted. If the data were given as a median, these values were standardized to the mean. Forty-one pharmacokinetics and 53 safety studies were included, but only one efficacy study was identified. The average maximum concentrations of isoniazid were expressed as supratherapeutic concentrations in adults (7.16 ± 4.85 μg/mL) and children (6.43 ± 3.87 μg/mL) in slow acetylators. The mean prevalence of drug-induced liver injury was 36.23 ± 19.84 in slow acetylators, which was significantly different from the intermediate (19.49 ± 18.20) and rapid (20.47 ± 20.68) acetylators. Subgroup analysis by continent showed that the highest mean drug-induced liver injury prevalence was in Asian slow acetylators (42.83 ± 27.61). The incidence of early treatment failure was decreased by genotype-guided isoniazid dosing in one study. Traditional weight-based dosing of isoniazid in most children and adults yielded therapeutic isoniazid levels (except for slow acetylators). Drug-induced liver injury was more commonly observed in slow acetylators. Genotype-guided dosing may prevent early treatment failure.
Topics: Adult; Child; Humans; Antitubercular Agents; Arylamine N-Acetyltransferase; Chemical and Drug Induced Liver Injury; Genotype; Isoniazid; Polymorphism, Genetic; Tuberculosis
PubMed: 38629592
DOI: 10.1111/cts.13795 -
Infection and Drug Resistance 2023Isavuconazole (ISA) is a second generation broad-spectrum triazole antifungal drug derived from voriconazole structure, and its oral capsules is currently the only oral... (Review)
Review
Isavuconazole (ISA) is a second generation broad-spectrum triazole antifungal drug derived from voriconazole structure, and its oral capsules is currently the only oral preparation approved for invasive mucormycosis. In recent years, population pharmacokinetic studies of ISA have been reported continuously. This paper aims to summarize the characteristics of population pharmacokinetic models of ISA in adults, and provide theoretical basis for individualized administration of ISA. We systematically searched PubMed, Embase, CNKI, Wanfang, VIP and other databases to collect population pharmacokinetic models published from the establishment of the database to March 2023. A total of 6 studies were included in this review, including healthy men and women, invasive fungal infections with malignant tumors or neutropenia, solid organ transplantation. The dose of ISA was 40-400mg for single-dose. The multiple-dose of ISA was 200mg every 8 hours for the first 48 hours and then 200mg once daily. All studies used a two-compartment model, first-order elimination. For oral formulations, except for one study that used first-order absorption, the others used Weibull absorption. Body mass index (BMI) was the most common covariable, followed by total body weight, lean body mass, race, sex, population type (healthy volunteers/patients), and creatinine clearance. These studies included several covariates, and the clearance rate (CL) was similar among populations. In the future, external validation and population pharmacokinetic studies in special populations such as patients with severe liver disease and ECMO support are needed.
PubMed: 38089964
DOI: 10.2147/IDR.S434622 -
Antibiotics (Basel, Switzerland) Sep 2023Oritavancin (ORI) is a semisynthetic lipoglycopeptide approved as a single 1200 mg dose intravenous infusion for the treatment of acute bacterial skin and skin structure... (Review)
Review
Oritavancin (ORI) is a semisynthetic lipoglycopeptide approved as a single 1200 mg dose intravenous infusion for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) caused by Gram-positive organisms in adults. The pharmacokinetic/pharmacodynamic (PK/PD) linear kinetic profile and long terminal half-life (~393 h) of ORI make it therapeutically attractive for the treatment of other Gram-positive infections for which prolonged therapy is needed. Multidose regimens are adopted in real-world clinical practice with promising results, but aggregated efficacy data are still lacking. A comprehensive search on PubMed/Medline, Scopus, Cochrane and Google Scholar databases was performed to include papers published up to the end of January 2023. All articles on ORI multiple doses usage, including case reports, with quantitative data and relevant clinical information were included. Two reviewers independently assessed papers against the inclusion/exclusion criteria and for methodological quality. Differences in opinion were adjudicated by a third party. From 1751 potentially relevant papers identified by this search, a total of 16 studies met the inclusion criteria and were processed further in the final data analysis. We extracted data concerning clinical response, bacteriologic response, mortality and adverse events (AEs). From the 16 included papers, 301 cases of treatment with multidose ORIs were identified. Multidose regimens comprised an initial ORI dose of 1200 mg followed by 1200 mg or 800 mg subsequent doses with a varying total number and frequency of reinfusions. The most often treated infections and isolates were osteomyelitis (148; 54.4%), ABSSSI (35; 12.9%) and cellulitis (14; 5.1%); and MRSA (121), MSSA (66), CoNS (17), (13) and (12), respectively. Clinical cure and improvement by multidose ORI regimens were observed in 85% (231/272) and 8% (22/272) patients, respectively. Multidose ORI was safe and well tolerated; the most frequent AEs were infusion-related reactions and hypoglycemia. A multidose ORI regimen may be beneficial in treating other Gram-positive infections besides ABSSSIs, with a good safety profile. Further studies are warranted to ascertain the superiority of one multidose ORI scheme or posology over the other.
PubMed: 37887199
DOI: 10.3390/antibiotics12101498 -
British Journal of Clinical Pharmacology Dec 2022This study aimed to review the studies evaluating the effect of the inflammatory state on voriconazole (VRZ) levels. (Review)
Review
AIMS
This study aimed to review the studies evaluating the effect of the inflammatory state on voriconazole (VRZ) levels.
METHODS
The study included randomized clinical trials, cohort studies, and case-control studies that focused on the influence of the inflammatory state on VRZ levels. Following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, relevant articles published until 2021 were searched in several databases, including PubMed, Embase, Web of Science and the Cochrane Library.
RESULTS
Twenty studies were included in this review, of which 15 described adult populations, three described paediatric populations, and two included both adult and paediatric populations. Seventeen studies used C-reactive protein (CRP) as an indicator of inflammation, six described a dose-response relationship for the effect of inflammation represented by CRP on VRZ concentrations, and four examined the effect of CRP on the metabolic rate of VRZ.
CONCLUSIONS
Our findings showed that the level of inflammation can significantly affect VRZ levels. However, the effect of inflammation on VRZ concentrations in children is controversial and must be analysed along with age. Clinicians dosing VRZ should take into account the patient's inflammatory state. The impact of inflammation on genotype-based dosing decisions requires further study to explain the high pharmacokinetic variability of VRZ.
Topics: Humans; Adult; Child; Voriconazole; Inflammation; C-Reactive Protein; Case-Control Studies
PubMed: 35973037
DOI: 10.1111/bcp.15495 -
PloS One 2018For nearly a century, no generic form of insulin has been available in the United States. However, the first biosimilar insulin, Basaglar, was approved by the U.S. Food... (Meta-Analysis)
Meta-Analysis Review
IMPORTANCE
For nearly a century, no generic form of insulin has been available in the United States. However, the first biosimilar insulin, Basaglar, was approved by the U.S. Food and Drug Administration in 2015, and subsequently Admelog and Lusduna in 2017.
OBJECTIVE
To summarize the scientific evidence comparing the safety, efficacy, pharmacokinetics, and pharmacodynamics of biosimilar and reference insulin products.
DATA SOURCES
We conducted a systematic review using PubMed, Cochrane, Embase, Latin America and Caribbean Health Sciences, South Asian Database of Controlled Clinical Trials, and IndiaMED from their inception through January 14, 2018.
STUDY SELECTION
We included randomized controlled trials (RCTs) comparing safety, clinical efficacy, pharmacokinetics and pharmacodynamics of any biosimilar insulin with a reference product in adults regardless of sample size and location.
DATA EXTRACTION AND SYNTHESIS
Two researchers independently reviewed all titles, abstracts and text; extracted data; and performed quality assessments.
MAIN OUTCOMES AND MEASURES
Efficacy, safety, pharmacokinetics, and pharmacodynamics of biosimilar and reference insulin products.
RESULTS
Of 6945 articles screened, 11 studies were included in the data synthesis. LY2963016, Basalog, Basalin, and MK-1293 were compared to Lantus while SAR342434 was compared to Humalog. Three trials enrolled healthy volunteers, five enrolled type 1 diabetics, and two enrolled type 2 diabetics. One study enrolled both healthy and type 1 diabetics. Of the eleven studies, six examined pharmacokinetic and/or pharmacodynamic parameters and five examined clinical efficacy and immunogenicity. All studies included adverse events. All PK and/or PD studies showed that comparable parameters of biosimilar and reference products were within the pre-specified equivalence margins. Clinical studies suggested similar clinical efficacy and immunogenicity. Adverse events were similar between the groups across all studies.
CONCLUSIONS AND RELEVANCE
Few published studies have compared biosimilar and reference insulins, though those that did suggest that the biosimilars have comparable safety and clinical efficacy as its reference product.
Topics: Biosimilar Pharmaceuticals; Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulins; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 29668697
DOI: 10.1371/journal.pone.0195012 -
Nutrients Jun 2018Magnesium (Mg) status has recently drawn close attention in chronic kidney disease and in kidney transplant recipients. This review aims to evaluate the body of evidence... (Review)
Review
Magnesium (Mg) status has recently drawn close attention in chronic kidney disease and in kidney transplant recipients. This review aims to evaluate the body of evidence linking hypomagnesemia to clinical consequences in these specific populations. After a brief summary of the main mechanisms involved in Mg regulation and of Mg status in end-stage renal disease, the review focuses on the relationship between hypomagnesemia and cardiovascular risk in kidney transplant recipients. A body of evidence in recent studies points to a negative impact of hypomagnesemia on post-transplant diabetes mellitus (PTDM) and cardiovascular risk, which currently represent the main threat for morbidity and mortality in kidney transplantation. Deleterious biological mechanisms induced by hypomagnesemia are also discussed. While data analysis enables us to conclude that hypomagnesemia is linked to the development of PTDM, studies prospectively evaluating the impact of hypomagnesemia correction after kidney transplantation are still lacking and needed.
Topics: Animals; Biomarkers; Cardiovascular Diseases; Diabetes Mellitus; Humans; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Magnesium; Magnesium Deficiency; Renal Elimination; Renal Reabsorption; Risk Factors; Treatment Outcome
PubMed: 29882768
DOI: 10.3390/nu10060729 -
Annals of Translational Medicine Feb 2022Polymyxin B (PMB) is a basic cyclic polypeptide antibiotic produced by , and is one of the last options for treating multi-drug-resistant negative bacterial infections... (Review)
Review
BACKGROUND
Polymyxin B (PMB) is a basic cyclic polypeptide antibiotic produced by , and is one of the last options for treating multi-drug-resistant negative bacterial infections in clinical practice. In recent years, many population pharmacokinetic studies of PMB have been conducted. This paper sought to comprehensively summarize the characteristics of population pharmacokinetic models of PMB and provide a theoretical basis for the individualized use of PMB.
METHODS
In this review, we systematically searched the PubMed and Embase databases to find articles on population pharmacokinetic models published from database establishment to August 2021.
RESULTS
A total of 10 studies were included in this review, including studies on various types of severe infections caused by multi-drug-resistant bacteria, hospital-acquired infections with fibrosis and other male and female populations, and a study of 2 continuous renal replacement therapy (CRRT) patients, aged 16-94 years, who received PMB doses of 10-360 mg/day (0.13-3.45 mg/kg/day), at an administration time of 0.5-6 hours. First-order linear elimination was used in all the studies; a 1-compartment model was used in 5 studies, and a 2-compartment model was used in 5 studies. The most common covariates were creatinine clearance (CrCL) and body weight.
DISCUSSION
Although these studies included several covariates and total clearance (CL) was close, but the external validation of some models was poorly correlated between the actual and predicted value. Novel or potential covariates represent important directions for further study.
PubMed: 35280373
DOI: 10.21037/atm-22-236 -
Biomedicine & Pharmacotherapy =... Nov 2020Bupleuri Radix (BR) is the dry root of Bupleurum chinense DC. and Bupleurum scorzonerifolium Willd. It has the functions of evacuation and antipyretic, soothing liver...
Bupleuri Radix (BR) is the dry root of Bupleurum chinense DC. and Bupleurum scorzonerifolium Willd. It has the functions of evacuation and antipyretic, soothing liver and relieving depression and often used to treat cold fever, chest and rib swelling pain, irregular menstruation, uterine prolapse, rectocele and other diseases. In this paper, the botany, traditional application, phytochemistry, pharmacology and toxicity of BR were reviewed. On the basis of limited literature, the analytical method, quality control, processing method, processing effect and pharmacokinetics of BR were summarized and analyzed for the first time. This review makes an in-depth discussion on the shortcomings of the current research on BR, and puts forward its own views and solutions. This has never been summarized in the previous review of BR. It is of great practical significance for future scholars to find a breakthrough point in the study of BR. So far, its mechanism has not been satisfactorily explained. Moreover, the comprehensive quality evaluation and multi-target network pharmacology of BR need to be further studied. In the future, more in vitro and in vivo experiments are needed to give full play to the therapeutic potential of BR.
Topics: Botany; Bupleurum; Drugs, Chinese Herbal; Humans; Medicine, Chinese Traditional; Phytochemicals; Plant Roots
PubMed: 32858498
DOI: 10.1016/j.biopha.2020.110679 -
Archives of Disease in Childhood Jan 2015To determine the extent of inter-individual variation in clearance of midazolam in children and establish which factors are responsible for this variation. (Review)
Review
OBJECTIVES
To determine the extent of inter-individual variation in clearance of midazolam in children and establish which factors are responsible for this variation.
METHODS
A systematic literature review was performed to identify papers describing the clearance of midazolam in children. The following databases were searched: Medline, Embase, International Pharmaceutical Abstracts, CINAHL and Cochrane Library. From the papers, the range in plasma clearance and the coefficient of variation (CV) in plasma clearance were determined.
RESULTS
25 articles were identified. Only 13 studies gave the full range of clearance values for individual patients. The CV was greater in critically ill patients (18%-170%) than non-critically ill patients (13%-54%). Inter-individual variation was a major problem in all age groups of critically ill patients. The CV was 72%-106% in preterm neonates, 18%-73% in term neonates, 31%-130% in infants, 21%-170% in children and 47%-150% in adolescents. The mean clearance was higher in children (1.1-16.7 mL/min/kg) than in neonates (0.78-2.5 mL/min/kg).
CONCLUSIONS
Large inter-individual variation was seen in midazolam clearance values in critically ill neonates, infants, children and adolescents.
Topics: Adolescent; Child; Critical Illness; Humans; Hypnotics and Sedatives; Infant; Infant, Newborn; Metabolic Clearance Rate; Midazolam
PubMed: 25281734
DOI: 10.1136/archdischild-2013-305720 -
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