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The Cochrane Database of Systematic... Dec 2023Many children undergo various surgeries, which often lead to acute postoperative pain. This pain influences recovery and quality of life. Non-steroidal anti-inflammatory... (Review)
Review
BACKGROUND
Many children undergo various surgeries, which often lead to acute postoperative pain. This pain influences recovery and quality of life. Non-steroidal anti-inflammatory drugs (NSAIDs), specifically cyclo-oxygenase (COX) inhibitors such as diclofenac, can be used to treat pain and reduce inflammation. There is uncertainty regarding diclofenac's benefits and harms compared to placebo or other drugs for postoperative pain.
OBJECTIVES
To assess the efficacy and safety of diclofenac (any dose) for acute postoperative pain management in children compared with placebo, other active comparators, or diclofenac administered by different routes (e.g. oral, rectal, etc.) or strategies (e.g. 'as needed' versus 'as scheduled').
SEARCH METHODS
We used standard, extensive Cochrane search methods. We searched CENTRAL, MEDLINE, and trial registries on 11 April 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) in children under 18 years of age undergoing surgery that compared diclofenac (delivered in any dose and route) to placebo or any active pharmacological intervention. We included RCTs comparing different administration routes of diclofenac and different strategies.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Our primary outcomes were: pain relief (PR) reported by the child, defined as the proportion of children reporting 50% or better postoperative pain relief; pain intensity (PI) reported by the child; adverse events (AEs); and serious adverse events (SAEs). We presented results using risk ratios (RR), mean differences (MD), and standardised mean differences (SMD), with the associated confidence intervals (CI).
MAIN RESULTS
We included 32 RCTs with 2250 children. All surgeries were done using general anaesthesia. Most studies (27) included children above age three. Only two studies had an overall low risk of bias; 30 had an unclear or high risk of bias in one or several domains. Diclofenac versus placebo (three studies) None of the included studies reported on PR or PI. We are very uncertain about the benefits and harms of diclofenac versus placebo on nausea/vomiting (RR 0.83, 95% CI 0.38 to 1.80; 2 studies, 100 children) and any reported bleeding (RR 3.00, 95% CI 0.34 to 26.45; 2 studies, 100 children), both very low-certainty evidence. None of the included studies reported SAEs. Diclofenac versus opioids (seven studies) We are very uncertain if diclofenac reduces PI at 2 to 24 hours postoperatively compared to opioids (median pain intensity 0.3 (interquartile range (IQR) 0.0 to 2.5) for diclofenac versus median 0.7 (IQR 0.1 to 2.4) in the opioid group; 1 study, 50 children; very low-certainty evidence). None of the included studies reported on PR or PI for other time points. Diclofenac probably results in less nausea/vomiting compared to opioids (41.0% in opioids, 31.0% in diclofenac; RR 0.75, 95% CI 0.58 to 0.96; 7 studies, 463 participants), and probably increases any reported bleeding (5.4% in opioids, 16.5% in diclofenac; RR 3.06, 95% CI 1.31 to 7.13; 2 studies, 222 participants), both moderate-certainty evidence. None of the included studies reported SAEs. Diclofenac versus paracetamol (10 studies) None of the included studies assessed child-reported PR. Compared to paracetamol, we are very uncertain if diclofenac: reduces PI at 0 to 2 hours postoperatively (SMD -0.45, 95% CI -0.74 to -0.15; 2 studies, 180 children); reduces PI at 2 to 24 hours postoperatively (SMD -0.64, 95% CI -0.89 to -0.39; 3 studies, 300 children); reduces nausea/vomiting (RR 0.47, 95% CI 0.25 to 0.87; 5 studies, 348 children); reduces bleeding events (RR 0.57, 95% CI 0.12 to 2.62; 5 studies, 332 participants); or reduces SAEs (RR 0.50, 95% CI 0.05 to 5.22; 1 study, 60 children). The evidence certainty was very low for all outcomes. Diclofenac versus bupivacaine (five studies) None of the included studies reported on PR or PI. Compared to bupivacaine, we are very uncertain about the effect of diclofenac on nausea/vomiting (RR 1.28, 95% CI 0.58 to 2.78; 3 studies, 128 children) and SAEs (RR 4.52, 95% CI 0.23 to 88.38; 1 study, 38 children), both very low-certainty evidence. Diclofenac versus active pharmacological comparator (10 studies) We are very uncertain about the benefits and harms of diclofenac versus any other active pharmacological comparator (dexamethasone, pranoprofen, fluorometholone, oxybuprocaine, flurbiprofen, lignocaine), and for different routes and delivery of diclofenac, due to few and small studies, no reporting of key outcomes, and very low-certainty evidence for the reported outcomes. We are unable to draw any meaningful conclusions from the numerical results.
AUTHORS' CONCLUSIONS
We remain uncertain about the efficacy of diclofenac compared to placebo, active comparators, or by different routes of administration, for postoperative pain management in children. This is largely due to authors not reporting on clinically important outcomes; unclear reporting of the trials; or poor trial conduct reducing our confidence in the results. We remain uncertain about diclofenac's safety compared to placebo or active comparators, except for the comparison of diclofenac with opioids: diclofenac probably results in less nausea and vomiting compared with opioids, but more bleeding events. For healthcare providers managing postoperative pain, diclofenac is a COX inhibitor option, along with other pharmacological and non-pharmacological approaches. Healthcare providers should weigh the benefits and risks based on what is known of their respective pharmacological effects, rather than known efficacy. For surgical interventions in which bleeding or nausea and vomiting are a concern postoperatively, the risks of adverse events using opioids or diclofenac for managing pain should be considered.
Topics: Humans; Child; Adolescent; Diclofenac; Acetaminophen; Pain, Postoperative; Nausea; Vomiting; Analgesics, Opioid; Bupivacaine
PubMed: 38078559
DOI: 10.1002/14651858.CD015087.pub2 -
Epilepsia Feb 2024Antiseizure medications (ASMs) are commonly categorized as enzyme-inducers and non-enzyme-inducers based on their propensity to enhance the metabolism of concomitantly... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Antiseizure medications (ASMs) are commonly categorized as enzyme-inducers and non-enzyme-inducers based on their propensity to enhance the metabolism of concomitantly administered drugs. This systematic review and network meta-analysis aimed to rank ASMs as cytochrome P450 3A (CYP3A)-inducers based on a comparative assessment of ASM-induced reduction in the concentrations of sensitive substrate drugs.
METHODS
The protocol was registered with PROSPERO (International Prospective Register of Systematic Reviews; CRD42022335846), and the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) standards were followed. We searched MEDLINE, Embase, and Cochrane until March 14, 2023 without an initial date restriction. Data were additionally obtained via the US Food and Drug Administration database. Studies had to be prospective, with ASM monotherapy for ≥5 days. The primary parameter was the magnitude of change in the area under the concentration-time curve of CYP3A substrates following treatment with the ASM. The standardized mean difference (SMD) was used as the point estimate for the indirect comparisons between ASMs using the pairwise method. Bias risk was assessed using the PKclin tool.
RESULTS
We identified 14 open-label, fixed-sequence studies with 370 participants. The effect size of 600 mg/day carbamazepine did not differ from those of 300 mg/day phenytoin (SMD = -.06, 95% confidence interval [CI] = -.18 to .07) and 200 mg/day cenobamate (SMD = -.11, 95% CI = -.26 to .04). Carbamazepine at 600 mg/day was the strongest CYP3A-inducer (P-score = .88), followed by carbamazepine 400 mg/day (.83), phenytoin 300 mg/day (.79), and cenobamate 200 mg/day (.73). Eslicarbazepine (800 mg/day) ranked higher than cenobamate 100 mg/day and oxcarbazepine 900 mg/day (.60, .39, and .37, respectively).
SIGNIFICANCE
Despite the limited number of studies, our network meta-analysis emphasizes that the magnitude of ASM effects on CYP3A substrate metabolism is a dose-dependent continuum. When possible, ASM classification as inducers should apply cutoff values tailored to the outcome. Prescribers should monitor plasma concentrations or clinical effects of CYP3A substrates and consider selecting concomitant medications accordingly.
Topics: Humans; Cytochrome P-450 CYP3A; Phenytoin; Network Meta-Analysis; Pharmaceutical Preparations; Carbamazepine; Benzodiazepines; Carbamates; Chlorophenols; Tetrazoles
PubMed: 38010146
DOI: 10.1111/epi.17822 -
Open Heart Nov 2023Clopidogrel is a P2Y inhibitor that has become a mainstay treatment following percutaneous intervention with drug-eluting stent placement to decrease restenosis and its...
INTRODUCTION
Clopidogrel is a P2Y inhibitor that has become a mainstay treatment following percutaneous intervention with drug-eluting stent placement to decrease restenosis and its potential complications, including sudden cardiac death and ischaemic strokes in patients with significant vascular disease.
AREAS COVERED
As a prodrug, the metabolism and efficacy of clopidogrel are contingent on the presence of wild-type CYP450 (CYP2C19) alleles. Genetic polymorphisms and variants are well known to impair its ability to prevent major adverse cardiovascular events in these patients, with inadequate response rates as high as 30% in previous publications. Patterns of allelic frequencies are expected to exhibit similarities between individuals of the same ancestry, ethnic group or geographic region. Accordingly, we seek to further elucidate worldwide prevalence rates for genetic polymorphisms in the CYP2C19-dependent metabolism of clopidogrel and review the potential of personalised CYP2C19 genotyping in clinical practice to mitigate this high treatment resistance and its associated burden on patients.
EXPERTS' COMMENTARY
Our findings support the consideration of genotyping before initiation of therapy to guide adequate dosage or substitutions of other P2Y inhibitors to promote personalised, precision medicine and to prevent adverse events when these therapies may inevitably fail in patients with variants of the CYP450 (CYP2C19) system.
Topics: Humans; Clopidogrel; Platelet Aggregation Inhibitors; Cytochrome P-450 CYP2C19; Drug-Eluting Stents; Polymorphism, Genetic
PubMed: 37963685
DOI: 10.1136/openhrt-2023-002436 -
Medicine and Science in Sports and... Feb 2024This study aimed to summarize and meta-analyze existing evidence regarding the influence of CYP1A2 genotypes on the acute effects of caffeine for exercise performance... (Meta-Analysis)
Meta-Analysis
PURPOSE
This study aimed to summarize and meta-analyze existing evidence regarding the influence of CYP1A2 genotypes on the acute effects of caffeine for exercise performance and to investigate the interaction between genotype, dosage, and timing of caffeine supplementation.
METHODS
Six databases were searched for studies determining the effect of caffeine (except mouth rinsing) on exercise performance between CYP1A2 genotypes. Three-level meta-analyses were performed using standardized mean differences (SMD; Hedge's g ) to determine the effect of caffeine on exercise outcomes within and between CYP1A2 genotypes (AA, AC, and CC). Meta-regressions were performed for dose, timing, and presence of reported conflict of interests (RCOI). A meta-analysis was also performed with placebo values to assess for imbalances between genotypes.
RESULTS
Thirteen studies, totaling 119 outcomes and 440 participants, were included (233 AA, 175 AC, ad 34 CC). Caffeine improved performance for AA (SMD = 0.30, 95% confidence interval [CI] = 0.21-0.39, P < 0.0001) and AC (SMD = 0.16, 95% CI = 0.06-0.25, P = 0.022) but worsened performance for CC (SMD = -0.22, 95% CI = -0.44 to -0.01, P < 0.0001). Dose affected only CC, with greater doses generating more positive SMD (CC-dose estimate: +0.19/1 mg·kg -1 body mass, 95% CI = 0.04-0.33, P = 0.01). Timing influenced only CC, with better performance with later onset of exercise after supplementation (CC-timing estimate: +0.01/min, 95% CI = 0.00-0.02, P = 0.02). RCOI only affected SMD of CC (CC-RCOI estimate: -0.57, 95% CI = -1.02 to -0.12, P = 0.01). After excluding studies with RCOI, no influence of genotype was seen (all P ≥ 0.19). Small, nonsignificant differences were seen in placebo between genotypes (SMD AA vs CC: -0.13; AA vs AC: -0.12; AC vs CC: -0.05; all P ≥ 0.26).
CONCLUSIONS
Caffeine improved performance for AA and AC but worsened performance for CC. Dose and timing moderated the efficacy of caffeine for CC only. Caution is advised because baseline differences and studies with RCOI could have influenced these results.
Topics: Humans; Caffeine; Cytochrome P-450 CYP1A2; Genotype; Exercise; Performance-Enhancing Substances
PubMed: 37844569
DOI: 10.1249/MSS.0000000000003313 -
Pain Physician Sep 2023Responsiveness to opioid analgesics differs among patients with acute postoperative pain. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Responsiveness to opioid analgesics differs among patients with acute postoperative pain.
OBJECTIVE
Our study presents the most recent evidence on the effect of genetic variations on postoperative pain, opioid consumption, nausea, and vomiting in patients treated with opioids.
STUDY DESIGN
An updated systematic review and meta-analysis on the association between single-nucleotide polymorphisms and opioids administered to patients with acute postoperative pain.
METHODS
PubMed, Embase, ISI Web of Science, and the Cochrane Library databases were searched for articles published from February 1, 2014, through December 31, 2021.
RESULTS
Added to the previous meta-analysis, 39 studies (a total of 7,455 patients) were included in the final meta-analysis. Highlights of the findings include: 1) human μ-opioid receptor gene 118G allele carriers required more opioids during the first postoperative 24 hours (standard mean difference [SMD] = -0.27; 95% CI,-0.40 to -0.14; P < 0.0001) and 48 hours (SMD = -0.52; 95% CI, -0.83 to -0.20; P = 0.001), and reported higher pain scores during the first 24 hours but not at the 48-hour postoperative period (SMD = -0.09, 95% CI, -0.15 to -0.03; P = 0.002) compared to homozygous 118AA patients. 2) patients with the CYP3A4 *1G allele required fewer opioids during the first 24-hour postoperative period (SMD = 0.59; 95% CI, 0.05 to 1.14; P = 0.03) compared to patients with the homozygous CYP3A4*1/*1 allele. 3) Adenosine triphosphate-binding cassette subfamily B member-1 (ABCB1) 3435T allele carriers required more opioids during the 48-hour postoperative period (SMD = -0.21; 95% CI, -0.38 to -0.04; P = 0.02) compared to homozygous CC carriers. 4) Catechol-O-methyl transferase 158A allele carriers required fewer opioids during the first 24-hour postoperative period (SMD = 0.33; 95% CI, 0.15 to 0.51; P = 0.0004) compared to homozygous GG carriers. No significant differences were observed in patients with CYP2D6*10 and ABCB1 G2677A/T genetic polymorphisms.
LIMITATIONS
Several loci were not analyzed in detail due to insufficient clinical data. Furthermore, nongenetic factors that affected analgesic efficacy and the clinical outcome of postoperative pain were not discussed and were not the aim of this meta-analysis.
CONCLUSIONS
In combination with previous systematic reviews and meta-analyses, our results indicate that the A118G allele variant of OPRM1 and the *1*1G allele variant of CYP3A4 have a profound influence on individual differences in opioid reactivity in patients with postoperative pain. Our results, together with the identification of additional single nucleotide polymorphisms in future studies, may provide a theoretical basis for precise clinical analgesia.
KEY WORDS
Single nucleotide polymorphism, postoperative pain, opioid, meta-analysis.
Topics: Humans; Analgesics, Opioid; Catechol O-Methyltransferase; Cytochrome P-450 CYP3A; Pain, Postoperative; Polymorphism, Single Nucleotide
PubMed: 37774182
DOI: No ID Found -
British Journal of Clinical Pharmacology Feb 2024This study aimed to provide up-to-date information on paediatric population pharmacokinetic models of tacrolimus and to identify factors influencing tacrolimus...
AIMS
This study aimed to provide up-to-date information on paediatric population pharmacokinetic models of tacrolimus and to identify factors influencing tacrolimus pharmacokinetic variability.
METHODS
Systematic searches in the Web of Science, PubMed, Scopus, Science Direct, Cochrane, EMBASE databases and reference lists of articles were conducted from inception to March 2023. All population pharmacokinetic studies of tacrolimus using nonlinear mixed-effect modelling in paediatric solid organ transplant patients were included.
RESULTS
Of the 21 studies reviewed, 62% developed from liver transplant recipients and 33% from kidney transplant recipients. Most studies used a 1-compartment model to describe tacrolimus pharmacokinetics. Body weight was a significant predictor for tacrolimus volume of distribution (Vd/F). The estimated Vd/F for 1-compartment models ranged from 20 to 1890 L, whereas the peripheral volume of distribution (Vp/F) for 2-compartment models was between 290 and 1520 L. Body weight, days post-transplant, CYP3A5 genotype or haematocrit were frequently reported as significant predictors of tacrolimus clearance. The estimated apparent clearance values range between 0.12 and 2.18 L/h/kg, with inter-individual variability from 13.5 to 110.0%. Only 29% of the studies assessed the generalizability of the models with external validation.
CONCLUSION
This review highlights the potential factors, modelling approaches and validation methods that impact tacrolimus pharmacokinetics in a paediatric population. The clinician could predict tacrolimus clearance based on body weight, CYP3A5 genotype, days post-transplant or haematocrit. Further research is required to determine the relationship between pharmacogenetics and tacrolimus pharmacodynamics in paediatric patients and confirm the applicability of nonlinear kinetics in this population.
Topics: Child; Humans; Body Weight; Cytochrome P-450 CYP3A; Genotype; Immunosuppressive Agents; Kidney Transplantation; Models, Biological; Organ Transplantation; Polymorphism, Single Nucleotide; Tacrolimus; Transplant Recipients
PubMed: 37714740
DOI: 10.1111/bcp.15909 -
Gene Dec 2023Identification of genetic risk factors for PCOS susceptibility. (Meta-Analysis)
Meta-Analysis Review
IMPORTANCE
Identification of genetic risk factors for PCOS susceptibility.
OBJECTIVE
To identify genetic risk variants of the genes involved in metabolic or inflammatory pathways.
DATA SOURCES
Relevant literature was identified and extracted from PubMed, Central Cochrane Library, Google Scholar, and Science Direct by using a set of keywords related to pre-determined genes up to 06 May 2023. Study selection and synthesis: PRISMA guidelines were followed to design the protocol which is registered in PROSPERO (CRD42023422501). Pooled odds ratio (OR) and 95% confidence interval (95% CI) for different gene variants were calculated under different genetic models (dominant model, recessive model, additive model, and allele model) by using Review Manager software 4.2.
MAIN OUTCOMES
Metabolic genetic variants FTO rs9939609, IL-6 rs1800795 and CAPN10 rs3842570, rs2975760, and RAB5B rs705702 are associated with PCOS risk.
RESULTS
Forty-four relevant articles have been identified for genes involved in metabolic (n = 23) or inflammatory pathways (n = 21). There is a significant association (p < 0.05) of IL-6 rs1800795 and FTO rs9939609 with increased risk.CAPN10 rs2975760 Ins allele is suggested as a protective factor among only the non-Asian population. Also, a significant association of CAPN10 rs2975760 and RAB5B rs705702 with increased risk among the Asian population is suggested. However, no significant association could be found between CAPN10 rs3792267, rs5030952, and SUMO1P1 rs2272046, and the risk of PCOS in any of the subpopulations analysed. In silico analysis suggests the deleterious effect of IL-6 rs1800795.
CONCLUSION
and relevance: The study suggests the role of various genetic variants for genetic predisposition to PCOS among different subpopulations.
Topics: Female; Humans; Alpha-Ketoglutarate-Dependent Dioxygenase FTO; Genetic Predisposition to Disease; Interleukin-6; Polycystic Ovary Syndrome; Polymorphism, Single Nucleotide; Risk Factors
PubMed: 37714276
DOI: 10.1016/j.gene.2023.147796 -
Obesity Reviews : An Official Journal... Dec 2023The extent to which genetic variations contribute to interindividual differences in weight loss and metabolic outcomes after bariatric surgery is unknown. Identifying... (Review)
Review
The extent to which genetic variations contribute to interindividual differences in weight loss and metabolic outcomes after bariatric surgery is unknown. Identifying genetic variants that impact surgery outcomes may contribute to clinical decision making. This review evaluates current evidence addressing the association of genetic variants with weight loss and changes in metabolic parameters after bariatric surgery. A search was conducted using Medline, Embase, Scopus, Web of Science, and Cochrane Library. Fifty-two eligible studies were identified. Single nucleotide polymorphisms (SNPs) at ADIPOQ (rs226729, rs1501299, rs3774261, and rs17300539) showed a positive association with postoperative change in measures of glucose homeostasis and lipid profiles (n = 4), but not with weight loss after surgery (n = 6). SNPs at FTO (rs11075986, rs16952482, rs8050136, rs9939609, rs9930506, and rs16945088) (n = 10) and MC4R (rs11152213, rs476828, rs2229616, rs9947255, rs17773430, rs5282087, and rs17782313) (n = 9) were inconsistently associated with weight loss and metabolic improvement. Four studies examining the UCP2 SNP rs660339 reported associations with postsurgical weight loss. In summary, there is limited evidence supporting a role for specific genetic variants in surgical outcomes after bariatric surgery. Most studies have adopted a candidate gene approach, limiting the scope for discovery, suggesting that the absence of compelling evidence is not evidence of absence.
Topics: Humans; Bariatric Surgery; Weight Loss; Polymorphism, Single Nucleotide; Alpha-Ketoglutarate-Dependent Dioxygenase FTO
PubMed: 37632325
DOI: 10.1111/obr.13626 -
Cureus Jul 2023Colorectal cancer (CRC) is a major global health concern, accounting for significant cancer-related morbidity and mortality worldwide. Despite advancements in early... (Review)
Review
Protective Effects of Long-Term Usage of Cyclo-Oxygenase-2 Inhibitors on Colorectal Cancer in Genetically Predisposed Individuals and Their Overall Effect on Prognosis: A Systematic Review.
Colorectal cancer (CRC) is a major global health concern, accounting for significant cancer-related morbidity and mortality worldwide. Despite advancements in early detection and treatment modalities, the prevention of CRC remains a critical goal. Cyclo-oxygenase-2 (COX-2) is an inducible enzyme involved in the production of pro-inflammatory prostaglandins, which play a crucial role in various cellular processes, including inflammation, cell proliferation, apoptosis, and angiogenesis. Elevated COX-2 expression has been consistently observed in colorectal tumors, indicating their role in the pathogenesis of cancer. COX-2 inhibitors, such as celecoxib and rofecoxib, have been studied as potentially effective treatment modalities due to their ability to decrease prostaglandin levels, which are generally higher in cancer patients. Aberrant prostaglandin production is linked to the adenoma-carcinoma sequence, during which adenomas turn dysplastic and accumulate enough damage to become malignant. COX-2 inhibitors have also been shown to modulate various signaling pathways involved in CRC development, such as wingless-related integration site/β-catenin (Wnt/β-catenin), mitogen-activated protein kinase (MAPK), and phosphoinositide-3-kinase-protein kinase B/Akt (PI3K/Akt) pathways. This systematic review aimed to evaluate the protective effects of long-term usage of COX-2 inhibitors on CRC in genetically predisposed individuals and their overall effect on the prognosis of the disease. The researchers conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines and collected data from several databases, including PubMed, PubMed Central, Cochrane Library, and Web of Science. The search strategy combined keywords related to CRC, COX-2 inhibitors, protective effects, and prognosis. They identified 1189 articles and shortlisted 26 full-text articles that met the eligibility criteria. Quality assessment tools, such as the Assessment of Multiple Systematic Review (AMSTAR) for systematic reviews, the Cochrane bias assessment tool for randomized control trials, the scale for the assessment of narrative review articles (SANRA) checklist for narrative reviews, and the Joanna Briggs Institute (JBI) tool for cross-sectional studies and case reports, are used. This review's conclusions will assist in determining the effectiveness of COX-2 inhibitors to prevent CRC. This review may also contribute to developing guidelines for clinicians to manage genetically predisposed individuals with CRC. Furthermore, the results of this review will shed light on the potential of COX-2 inhibitors as a preventive measure against CRC in genetically predisposed individuals.
PubMed: 37588311
DOI: 10.7759/cureus.41939 -
Pharmacogenomics Jul 2023Sirolimus is an antiproliferative and immunosuppressive compound inhibiting the mTOR pathway, which is often activated in congenital low-flow vascular malformations.... (Review)
Review
Sirolimus is an antiproliferative and immunosuppressive compound inhibiting the mTOR pathway, which is often activated in congenital low-flow vascular malformations. Studies have demonstrated the efficacy of sirolimus for this disease. Studies in kidney transplant patients suggest that genetic variants can influence these pharmacokinetic parameters. Therefore, a systematic literature search was performed to gain insight into pharmacogenetic studies with sirolimus. Most studies investigated and , with inconsistent results. No pharmacogenetic studies focusing on sirolimus have been performed for low-flow vascular malformations. We analyzed two common variants of and ( and , respectively) in patients (n = 59) with congenital low-flow vascular malformations treated with sirolimus. No association with treatment outcome was identified in this small cohort of patients.
Topics: Humans; Sirolimus; Cytochrome P-450 CYP3A; Polymorphism, Single Nucleotide; Immunosuppressive Agents; Kidney Transplantation; Tacrolimus; Genotype
PubMed: 37551646
DOI: 10.2217/pgs-2022-0147