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Clinical Pharmacokinetics May 2024Although little information is available on the pharmacokinetics (PK) of monoclonal antibodies (mAbs) during pregnancy, multiple mAbs are being used during pregnancy for...
BACKGROUND AND OBJECTIVE
Although little information is available on the pharmacokinetics (PK) of monoclonal antibodies (mAbs) during pregnancy, multiple mAbs are being used during pregnancy for various indications. The aim of this systematic literature review was to characterize the PK of mAbs throughout pregnancy.
METHODS
A systematic literature search was carried out in PubMed and Embase on 21 April 2023. Articles were included when information on PK or exposure parameters of mAbs in pregnant women was available.
RESULTS
A total of 42 relevant articles were included, of which eight discussed adalimumab, three certolizumab pegol, five eculizumab, one golimumab, 12 infliximab (IFX), two natalizumab, one canakinumab, one omalizumab, five tocilizumab, eight ustekinumab, and five vedolizumab. One of the 42 studies reported information on clearance (CL) and volume of distribution (VD) of IFX; all other studies only reported on serum concentrations in the pre-pregnancy state, different trimesters, and the postpartum period. For all of the assessed mAbs except IFX, serum concentrations were similar to concentrations in the pre-pregnancy state or modestly decreased. In contrast, IFX trough concentrations generally increased in the second and third trimesters in comparison to the non-pregnant state.
CONCLUSION
Available information suggests that the anatomical and physiological changes throughout pregnancy may have meaningful effects on the PK of mAbs. For most mAbs (not IFX), modestly higher dosing (per mg) maybe needed during pregnancy to sustain a similar serum exposure compared to pre-pregnancy.
Topics: Humans; Pregnancy; Female; Antibodies, Monoclonal; Pregnancy Complications
PubMed: 38583128
DOI: 10.1007/s40262-024-01370-7 -
Journal of Infection and Public Health May 2024Colistin is a viable option for multidrug resistant gram-negative bacteria emerged from inappropriate antibiotic use. Nonetheless, suboptimal colistin concentrations and... (Meta-Analysis)
Meta-Analysis
Clinical outcomes of colistin methanesulfonate sodium in correlation with pharmacokinetic parameters in critically ill patients with multi-drug resistant bacteria-mediated infection: A systematic review and meta-analysis.
BACKGROUND
Colistin is a viable option for multidrug resistant gram-negative bacteria emerged from inappropriate antibiotic use. Nonetheless, suboptimal colistin concentrations and nephrotoxicity risks hinder its clinical use. Thus, the aim of this study is to investigate clinical outcomes in correlation with pharmacokinetic differences and infection types in critically ill patients on intravenous colistin methanesulfornate sodium (CMS).
METHODS
A systematic literature search of Embase, Google Scholars, and PubMed was performed to identify clinical trials evaluating pharmacokinetic parameters along with clinical outcomes of CMS treatment from inception to July 2023. The pooled analyses of clinical impact of CMS on nephrotoxicity, mortality, clinical cure, and colistin concentration at steady state (C) were performed. This study was registered in the PROSPERO (CRD 42023456120).
RESULTS
Total of 695 critically ill patients from 17 studies were included. The mortality was substantially lower in clinically cured patients (OR 0.05; 95% CI 0.02 - 0.14), whereas the mortality rate was statistically insignificant between nephrotoxic and non-nephrotoxic patients. Inter-patient variability of pharmacokinetic parameters of CMS and colistin was observed in critically ill patients. The standard mean differences of C were statistically insignificant between clinically cure and clinically failure groups (standard mean difference (SMD) -0.25; 95% CI -0.69 - 0.19) and between nephrotoxic and non-nephrotoxic groups (SMD 0.67; 95% CI -0.27-1.61). The clinical cure rate is substantially lower in pneumonia patients (OR 0.09; 95% CI 0.01 - 0.56), and pharmacokinetic parameters pertaining to microbiological cure were different among strains.
CONCLUSION
The mortality rate was substantially lower in clinically cured patients with CMS. However, no significant differences in C of colistin were examined to determine the impact of pharmacokinetic differences on clinical outcomes including mortality rate and nephrotoxicity risk. Nevertheless, the clinical cure rate is substantially lower in patients with respiratory infection than patients with urinary tract infection.
Topics: Humans; Colistin; Critical Illness; Anti-Bacterial Agents; Bacterial Infections; Bacteria; Mesylates; Gram-Negative Bacterial Infections
PubMed: 38554590
DOI: 10.1016/j.jiph.2024.03.021 -
Medical Science Monitor : International... Mar 2024BACKGROUND Placenta accreta syndrome (PAS) can lead to severe obstetric bleeding, and can be life-threatening. This study aimed to assess the precision of radiomics... (Meta-Analysis)
Meta-Analysis
BACKGROUND Placenta accreta syndrome (PAS) can lead to severe obstetric bleeding, and can be life-threatening. This study aimed to assess the precision of radiomics features derived from magnetic resonance imaging (MRI) for diagnosing PAS. MATERIAL AND METHODS A comprehensive search was conducted in the databases PubMed, Embase, Web of Science, and the Cochrane library from inception to October 2023. We included diagnostic accuracy studies utilizing radiomics-MRI in PAS patients, with histopathology serving as the reference standard. The overall diagnostic odds ratio (DOR), sensitivity, specificity, and area under the curve (AUC) were computed to gauge the diagnostic accuracy of MRI-based radiomic features in PAS patients. Quality assessment was performed using the Quality Assessment of Diagnostic Accuracy Studies 2. Statistical analyses were carried out using Stata 14.2, MetaDiSc 1.4, and Review Manager 5.3 software. RESULTS Seven studies involving 672 patients were incorporated. The aggregated DOR, sensitivity, specificity, and AUC for radiomics in detecting PAS were 78% (confidence interval32, 191), 87% (76%, 93%), 92% (89%, 94%), and 0.93 (0.91-0.95), respectively. The meta-analysis revealed notable heterogeneity among the included studies, with no evidence of a threshold effect. Subgroup analysis demonstrated that, in comparison to manual segmentation and validation groups with ≤100 cases and internal validation datasets, automated segmentation, validation groups with >100 cases, and external validation datasets exhibited superior diagnostic performance . CONCLUSIONS Our findings indicate that MRI-based radiomic features perform well in assessing the diagnostic risk of PAS during prenatal diagnosis. This noninvasive and convenient tool may prove valuable in facilitating the identification of PAS.
Topics: Female; Pregnancy; Humans; Placenta Accreta; Radiomics; Area Under Curve; Databases, Factual; Magnetic Resonance Imaging
PubMed: 38486373
DOI: 10.12659/MSM.943461 -
The Journal of Antimicrobial... May 2024Pharmacokinetic/pharmacodynamic (PK/PD) indices are widely used for the selection of optimum antibiotic doses. For β-lactam antibiotics, fT>MIC, best relates antibiotic...
BACKGROUND
Pharmacokinetic/pharmacodynamic (PK/PD) indices are widely used for the selection of optimum antibiotic doses. For β-lactam antibiotics, fT>MIC, best relates antibiotic exposure to efficacy and is widely used to guide the dosing of β-lactam/β-lactamase inhibitor (BLI) combinations, often without considering any PK/PD exposure requirements for BLIs.
OBJECTIVES
This systematic review aimed to describe the PK/PD exposure requirements of BLIs for optimal microbiological efficacy when used in combination with β-lactam antibiotics.
METHODS
Literature was searched online through PubMed, Embase, Web of Science, Scopus and Cochrane Library databases up to 5 June 2023. Studies that report the PK/PD index and threshold concentration of BLIs approved for clinical use were included. Narrative data synthesis was carried out to assimilate the available evidence.
RESULTS
Twenty-three studies were included. The PK/PD index that described the efficacy of BLIs was fT>CT for tazobactam, avibactam and clavulanic acid and fAUC0-24/MIC for relebactam and vaborbactam. The optimal magnitude of the PK/PD index is variable for each BLI based on the companion β-lactam antibiotics, type of bacteria and β-lactamase enzyme gene transcription levels.
CONCLUSIONS
The PK/PD index that describes the efficacy of BLIs and the exposure measure required for their efficacy is variable among inhibitors; as a result, it is difficult to make clear inference on what the optimum index is. Further PK/PD profiling of BLI, using preclinical infection models that simulate the anticipated mode(s) of clinical use, is warranted to streamline the exposure targets for use in the optimization of dosing regimens.
Topics: beta-Lactamase Inhibitors; Humans; Anti-Bacterial Agents; Microbial Sensitivity Tests; beta-Lactams; beta-Lactamases
PubMed: 38459763
DOI: 10.1093/jac/dkae058 -
Redox Biology May 2024This systematic review provides an overview of the available evidence on the inter-individual variability (IIV) in the absorption, distribution, metabolism, and... (Review)
Review
This systematic review provides an overview of the available evidence on the inter-individual variability (IIV) in the absorption, distribution, metabolism, and excretion (ADME) of phenolic metabolites and its determinants. Human studies were included investigating the metabolism and bioavailability of (poly)phenols and reporting IIV. One hundred fifty-three studies met the inclusion criteria. Inter-individual differences were mainly related to gut microbiota composition and activity but also to genetic polymorphisms, age, sex, ethnicity, BMI, (patho)physiological status, and physical activity, depending on the (poly)phenol sub-class considered. Most of the IIV has been poorly characterised. Two major types of IIV were observed. One resulted in metabolite gradients that can be further classified into high and low excretors, as seen for all flavonoids, phenolic acids, prenylflavonoids, alkylresorcinols, and hydroxytyrosol. The other type of IIV is based on clusters of individuals defined by qualitative differences (producers vs. non-producers), as for ellagitannins (urolithins), isoflavones (equol and O-DMA), resveratrol (lunularin), and preliminarily for avenanthramides (dihydro-avenanthramides), or by quali-quantitative metabotypes characterized by different proportions of specific metabolites, as for flavan-3-ols, flavanones, and even isoflavones. Future works are needed to shed light on current open issues limiting our understanding of this phenomenon that likely conditions the health effects of dietary (poly)phenols.
Topics: Humans; Biological Availability; Phenols; Flavonoids; Isoflavones; Diet
PubMed: 38428187
DOI: 10.1016/j.redox.2024.103095 -
Scientific Data Feb 2024The cutaneous absorption parameters of xenobiotics are crucial for the development of drugs and cosmetics, as well as for assessing environmental and occupational...
The cutaneous absorption parameters of xenobiotics are crucial for the development of drugs and cosmetics, as well as for assessing environmental and occupational chemical risks. Despite the great variability in the design of experimental conditions due to uncertain international guidelines, datasets like HuskinDB have been created to report skin absorption endpoints. This review updates available skin permeability data by rigorously compiling research published between 2012 and 2021. Inclusion and exclusion criteria have been selected to build the most harmonized and reusable dataset possible. The Generative Topographic Mapping method was applied to the present dataset and compared to HuskinDB to monitor the progress in skin permeability research and locate chemotypes of particular concern. The open-source dataset (SkinPiX) includes steady-state flux, maximum flux, lag time and permeability coefficient results for the substances tested, as well as relevant information on experimental parameters that can impact the data. It can be used to extract subsets of data for comparisons and to build predictive models.
Topics: Permeability; Skin; Skin Absorption; Xenobiotics; Datasets as Topic; Humans
PubMed: 38383523
DOI: 10.1038/s41597-024-03026-4 -
The Journal of Infection Mar 2024Interest in phages as adjunctive therapy to treat difficult infections has grown in the last decade. However, phage dosing and delivery for orthopedic infections have... (Review)
Review
OBJECTIVES
Interest in phages as adjunctive therapy to treat difficult infections has grown in the last decade. However, phage dosing and delivery for orthopedic infections have not been systematically summarized.
METHODS
Following PRISMA-ScR guidelines, we conducted a SCOPING review through September 1st, 2023, of MEDLINE, Embase, Web of Science Core Collection, and Cochrane Central.
RESULTS
In total, 77 studies were included, of which 19 (24.7%) were in vitro studies, 17 (22.1%) were animal studies, and 41 (53.2%) were studies in humans. A total of 137 contemporary patients receiving phage therapy are described.
CONCLUSIONS
Direct phage delivery remains the most studied form of phage therapy, notably in prosthetic joint infections, osteomyelitis, and diabetic foot ulcers. Available evidence describing phage therapy in humans suggests favorable outcomes for orthopedic infections, though this evidence is composed largely of low-level descriptive studies. Several phage delivery devices have been described, though a lack of comparative and in-human evidence limits their therapeutic application. Limitations to the use of phage therapy for orthopedic infections that need to be overcome include a lack of understanding related to optimal dosing and phage pharmacokinetics, bacterial heterogeneity in an infection episode, and phage therapy toxicity.
Topics: Animals; Humans; Phage Therapy; Bacteria; Osteomyelitis; Arthritis, Infectious; Bacterial Infections
PubMed: 38373574
DOI: 10.1016/j.jinf.2024.106125 -
Annals of Intensive Care Feb 2024The two latest studies on prolonged versus intermittent use of β-lactam antibiotics in patients with sepsis did not reach consistent conclusions, further contributing... (Review)
Review
BACKGROUND
The two latest studies on prolonged versus intermittent use of β-lactam antibiotics in patients with sepsis did not reach consistent conclusions, further contributing to the controversy surrounding the effectiveness of the prolonged β-lactam antibiotics infusion strategy. We conducted a systemic review and meta-analysis to evaluate the efficacy and safety of prolonged and intermittent β-lactam infusion in adult patients with sepsis.
METHODS
We systematically searched PubMed, EMBASE, and Cochrane Library databases for original randomized controlled trials comparing prolonged and intermittent β-lactam infusion in sepsis patients. A random-effects model was used to evaluate mortality, clinical success, microbiological success, and adverse events. We also conducted subgroup analyses to explore the impact of various factors on the mortality rates. Relative risk (RR) and corresponding 95% confidence intervals (CIs) were used to calculate the overall effect sizes for dichotomous outcomes. This meta-analysis was registered in PROSPERO (CRD42023463905).
RESULTS
We assessed 15 studies involving 2130 patients. In our comprehensive assessment, we found a significant reduction in all-cause mortality (RR, 0.83; 95% CI 0.72-0.97; P = 0.02) and a notable improvement in clinical success (RR, 1.16; 95% CI 1.03-1.31; P = 0.02) in the prolonged infusion group compared to the intermittent infusion group, whereas microbiological success did not yield statistically significant results (RR, 1.10; 95% CI 0.98-1.23; P = 0.11). No significant differences in adverse events were observed between the two groups (RR, 0.91; 95% CI 0.64-1.29; P = 0.60). Additionally, remarkable conclusions were drawn from subgroup analyses including studies with sample sizes exceeding 20 individuals per group (RR, 0.84; 95%CI 0.72-0.98; P = 0.03), research conducted post-2010 (RR, 0.84; 95%CI 0.72-0.98; P = 0.03), cases involving infections predominantly caused by Gram-negative bacteria (RR, 0.81; 95%CI 0.68-0.96; P = 0.02), as well as the administration of a loading dose (RR, 0.84; 95% CI 0.72-0.97; P = 0.02) and the use of penicillin (RR, 0.61; 95% CI 0.38-0.98; P = 0.04).
CONCLUSIONS
Compared to intermittent infusion, prolonged infusion of β-lactam antibiotics significantly decreases all-cause mortality among patients with sepsis and enhances clinical success without increasing adverse events.
PubMed: 38368588
DOI: 10.1186/s13613-024-01263-9 -
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 -
BMC Nephrology Feb 2024This study aimed to investigate the association between cytochrome P450 (CYP) 3A4*22 and cytochrome P450 oxidoreductase (POR)*28 variations and the pharmacokinetics of... (Meta-Analysis)
Meta-Analysis
PURPOSE
This study aimed to investigate the association between cytochrome P450 (CYP) 3A4*22 and cytochrome P450 oxidoreductase (POR)*28 variations and the pharmacokinetics of tacrolimus.
METHODS
Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science (SCI), MEDLINE, and Embase were systematically searched from inception to August 2022. The outcomes were weight-adjusted daily dose and dose-adjusted trough concentration (C/Dose).
RESULTS
The study included 2931 renal transplant recipients from 18 publications. Weight-adjusted daily dose of CYP3A4*1/*1 carriers was 0.04 (WMD = 0.04, 95% CI: 0.02 to 0.06), 0.03 (WMD = 0.03, 95% CI: 0.02 to 0.05), 0.02 (WMD = 0.02, 95% CI: 0.01 to 0.03), or 0.02 mg/kg/day (WMD = 0.02, 95% CI: 0.00 to 0.04) higher than CYP3A4*22 carriers in Caucasians at 1 month, 3 months, 6 months, or 12 months post-transplantation. Conversely, C0/Dose was lower for CYP3A4*1/*1 carriers at 3 days (SMD = -0.35, 95% CI: -0.65 to -0.06), 1 month (SMD = -0.67, 95% CI: -1.16 to -0.18), 3 months (SMD = -0.60, 95% CI: -0.89 to -0.31), 6 months (SMD = -0.76, 95% CI: -1.49 to -0.04), or 12 months post-transplantation (SMD = -0.69, 95% CI: -1.37 to 0.00). Furthermore, C/Dose of POR*1/*1 carriers was 22.64 (WMD = 22.64, 95% CI: 2.54 to 42.74) or 19.41 (ng/ml)/(mg/kg/day) (WMD = 19.41, 95% CI: 9.58 to 29.24) higher than POR*28 carriers in CYP3A5 expressers at 3 days or 7 days post-transplantation, and higher in Asians at 6 months post-transplantation (SMD = 0.96, 95% CI: 0.50 to 1.43).
CONCLUSIONS
CYP3A4*22 variant in Caucasians restrains the metabolism of tacrolimus, while POR*28 variant in CYP3A5 expressers enhances the metabolism of tacrolimus for renal transplant recipients. However, further well-designed prospective studies are necessary to substantiate these conclusions given some limitations.
Topics: Humans; Tacrolimus; Cytochrome P-450 CYP3A; Immunosuppressive Agents; Kidney Transplantation; Prospective Studies; Polymorphism, Single Nucleotide; Transplant Recipients; Genotype
PubMed: 38321419
DOI: 10.1186/s12882-024-03467-4