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Drug Design, Development and Therapy 2024Several population pharmacokinetic (PPK) models of B cell lymphoma-2 (BCL-2) venetoclax (VEN) have been developed and published to characterize the influencing factors... (Review)
Review
Several population pharmacokinetic (PPK) models of B cell lymphoma-2 (BCL-2) venetoclax (VEN) have been developed and published to characterize the influencing factors of pharmacokinetics in hematologic malignancies. This review described PPK models of VEN examining the magnitude and types of covariate effects in PK parameters, as well as identified areas that require further investigation in order to facilitate their use. Currently, there are six analyses on PPK models of VEN summarized in this review. Most analyses described the pharmacokinetics of VEN with a two-compartment model and all covariates are categorical. The median estimated apparent clearance (CL/F) was 446 L/Day and apparent volume of distribution of the central compartment (V/F) was 114.5 L. The median IIV of CL/F reported was 39.5% and V/F was 46.7%. Most commonly, CYP3A inhibitors, OATP1B3 inhibitors and rituximab co-administration were found to be significant covariates on CL/F. In addition, sex and population were influential covariates on V/F. A detailed description of the characteristics of PPK models of VEN is provided in this review, as well as the effects of covariates on the PK parameters. For future development of the VEN PPK model, CYP3A inhibitors, rituximab co-administration, OATP1B1 transporter inhibitors, sex, population, and food might be considered. Further research and comprehensive investigations should be undertaken to explore reference ranges for therapeutic drug monitoring, define the potential role of patients with cerebrospinal fluid complications, and assess new or potential covariates. These endeavors will facilitate the development of personalized VEN therapy.
Topics: Humans; Hematologic Neoplasms; Sulfonamides; Bridged Bicyclo Compounds, Heterocyclic; Antineoplastic Agents; Models, Biological
PubMed: 38828021
DOI: 10.2147/DDDT.S458927 -
Kidney & Blood Pressure Research Jun 2024Opioid analgesics are often used to manage moderate to severe pain. A significant proportion of patients taking opioids have compromised kidney function. This systematic...
INTRODUCTION
Opioid analgesics are often used to manage moderate to severe pain. A significant proportion of patients taking opioids have compromised kidney function. This systematic review aimed to examine the available evidence on the safety and analgesic effect of opioid use in adults with kidney disease.
METHODS
We searched eight electronic databases from inception to 26th January 2023. Published original research articles in English reporting on opioid use and pharmacokinetic data among adults with reduced renal function were included. Article screening, data extraction, and quality assessment were conducted by at least two investigators independently. This review was registered prospectively on PROSPERO (ID: CRD42020159091).
RESULTS
There were 32 observational studies included, 14 of which reported on morphine use, three involved fentanyl use, two involved hydromorphone use and 13 articles reported on other opioids including codeine, dihydrocodeine, and buprenorphine.
CONCLUSION
There is limited and low-quality evidence to inform the safety and analgesic effect of opioid use in reduced renal function. Morphine remains the opioid for which there is the most evidence available on safety and analgesic effect in the context of renal disease. Greater caution and consideration of potential risks and benefits should be applied when using other opioids. Further high-quality studies examining clinical outcomes associated with the use of different opioids and opioid doses in renal disease are warranted.
PubMed: 38824925
DOI: 10.1159/000538258 -
Therapeutic Advances in Medical Oncology 2024Compared with anti-infective drugs, immunosuppressants and other fields, the application of therapeutic drug monitoring (TDM) in oncology is somewhat limited. (Review)
Review
BACKGROUND
Compared with anti-infective drugs, immunosuppressants and other fields, the application of therapeutic drug monitoring (TDM) in oncology is somewhat limited.
OBJECTIVE
We aimed to provide a comprehensive understanding of TDM guidelines for antineoplastic drugs and to promote the development of individualized drug therapy in oncology.
DESIGN
This study type is a systematic review.
DATA SOURCES AND METHODS
This study was performed and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement. Databases including PubMed, Embase, the official websites of TDM-related associations and Chinese databases were comprehensively searched up to March 2023. Two investigators independently screened the literature and extracted data. The methodological and reporting quality was evaluated using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) and the Reporting Items for Practice Guidelines in Healthcare (RIGHT), respectively. Recommendations and quality evaluation results were presented by visual plots. This study was registered in PROSPERO (No. CRD42022325661).
RESULTS
A total of eight studies were included, with publication years ranging from 2014 to 2022. From the perspective of guideline development, two guidelines were developed using evidence-based methods. Among the included guidelines, four guidelines were for cytotoxic antineoplastic drugs, three for small molecule kinase inhibitors, and one for antineoplastic biosimilars. Currently available guidelines and clinical practice provided recommendations of individualized medication in oncology based on TDM, as well as influencing factors. With regard to methodological quality based on AGREE II, the average overall quality score was 55.21%. As for the reporting quality by RIGHT evaluation, the average reporting rate was 53.57%.
CONCLUSION
From the perspective of current guidelines, TDM in oncology is now being expanded from cytotoxic antineoplastic drugs to newer targeted treatments. Whereas, the types of antineoplastic drugs involved are still small, and there is still room for quality improvement. Furthermore, the reflected gaps warrant future studies into the exposure-response relationships and population pharmacokinetics models.
PubMed: 38812991
DOI: 10.1177/17588359241250130 -
Clinical Pharmacokinetics Jun 2024Managing drug-food interactions is essential for optimizing the effectiveness and safety profile of quinolones. Following PRISMA guidelines, we systematically reviewed... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVE
Managing drug-food interactions is essential for optimizing the effectiveness and safety profile of quinolones. Following PRISMA guidelines, we systematically reviewed the influence of dietary interventions on the bioavailability of 22 quinolones.
METHODS
All studies describing or investigating the impact of food, beverages, antacids, and mineral supplements on pharmacokinetic parameters or pharmacokinetic/pharmacodynamic indices of orally taken quinolones were considered for inclusion. We excluded reviews, in vitro and in silico studies, studies performed on animals, and those involving alcohol. We performed the search in Medline (via PubMed), Embase, and Cochrane Library, covering reports from database inception to December 2022. We used the following tools to assess the risk of bias: version 2 of the Cochrane risk-of-bias tool for parallel trials, the Cochrane risk-of-bias tool for cross-over studies, and the NIH quality assessment tool for before-after studies. We performed quantitative analyses for each quinolone if two or more food-effect studies with specified and comparable study designs were available. If meta-analyses were not applicable, we qualitatively summarized the results.
RESULTS
We included 109 studies from 101 reports. Meta-analyses were conducted for 12 antibiotics and qualitative synthesis was employed for the remaining drugs. Of the studies, 60.5% were open-label, cross-over, as recommended by FDA. We judged 46% of studies as having a high risk of bias and only 4% of having a low risk of bias. Among 19 quinolones with available food impact data, 14 (74%) had potentially clinically important interactions. For nalidixic acid, oxolinic acid, and tosufloxacin, food exerted a high positive impact on bioavailability (AUC or C increased by > 45%), whereas, for all the remaining drugs, postprandial absorption was lower. The most significant negative influence of food (AUC or C decreased by > 40%) occurred for delafloxacin capsules and norfloxacin, whereas the moderate influence (AUC or C decreased by 30-40%) occurred for nemonoxacin and rufloxacin. All 14 analysed quinolones showed a substantial reduction in bioavailability when co-administered with antacids and mineral supplements, except for calcium preparations. The impact of beverages was evaluated for 10 quinolones, with 50% experiencing significantly reduced absorption in the presence of milk (the highest negative impact for ciprofloxacin). Moreover, both ciprofloxacin and levofloxacin demonstrated compromised bioavailability when consumed with orange juice, particularly calcium-fortified.
DISCUSSION
Several factors may influence interactions, including the physicochemical characteristics of quinolones, the type of intervention, drug formulation, and the patient's health status. We assessed the quality of evidence as low due to the poor actuality of included studies, their methodological diversity, and uneven data availability for individual drugs.
Topics: Quinolones; Humans; Food-Drug Interactions; Biological Availability; Dietary Supplements; Anti-Bacterial Agents; Antacids; Diet; Administration, Oral
PubMed: 38807006
DOI: 10.1007/s40262-024-01377-0 -
Acta Neurologica Belgica May 2024Chronic subdural hematoma (CSDH) is a prevalent type of intracranial hemorrhage. Surgical interventions, such as Twist Drill Craniostomy and Burr Hole Craniostomy, are... (Review)
Review
BACKGROUND
Chronic subdural hematoma (CSDH) is a prevalent type of intracranial hemorrhage. Surgical interventions, such as Twist Drill Craniostomy and Burr Hole Craniostomy, are employed for its treatment. However, limited information exists regarding the impact of postoperative head position (supine vs. elevated) on clinical outcomes. We aim to assess whether patients' head position after surgery influences their prognosis.
METHOD
We conducted a PRISMA-compliant systematic review and meta-analysis. Our search encompassed PubMed, Cochrane CENTRAL, Scopus, Web of Science, and Embase databases to identify relevant published studies. Data were meticulously extracted, pooled using a fixed model, and reported as risk ratios (RR) with 95% confidence intervals (CI). Statistical analysis was performed using R and Stata MP v.17.
RESULTS
Five studies involving 284 patients were included in our meta-analysis. We focused on three primary clinical outcomes, comparing the supine and elevated header positions. Notably, there was no statistically significant difference between the supine and elevated positions in terms of recurrence rate (RR 0.77, 95% CI [0.44, 1.37]), second intervention for recurrence (RR 1.07, 95% CI [0.42, 2.78]) and postoperative complications (RR 1.16, 95% CI [0.70, 1.92]).
CONCLUSION
Current studies have proved no difference between supine and elevated bed header positions regarding recurrence rate, second intervention for recurrence, and postoperative complications. Future RCTs with long-term follow-ups are recommended.
PubMed: 38802719
DOI: 10.1007/s13760-024-02571-4 -
Breast Cancer Research : BCR May 2024The proportion of patients with breast cancer and obesity is increasing. While the therapeutic landscape of breast cancer has been expanding, we lack knowledge about the... (Review)
Review
BACKGROUND
The proportion of patients with breast cancer and obesity is increasing. While the therapeutic landscape of breast cancer has been expanding, we lack knowledge about the potential differential efficacy of most drugs according to the body mass index (BMI). Here, we conducted a systematic review on recent clinical drug trials to document the dosing regimen of recent drugs, the reporting of BMI and the possible exclusion of patients according to BMI, other adiposity measurements and/or diabetes (leading comorbidity of obesity). We further explored whether treatment efficacy was evaluated according to BMI.
METHODS
A search of Pubmed and ClinicalTrials.gov was performed to identify phase I-IV trials investigating novel systemic breast cancer treatments. Dosing regimens and exclusion based on BMI, adiposity measurements or diabetes, documentation of BMI and subgroup analyses according to BMI were assessed.
RESULTS
495 trials evaluating 26 different drugs were included. Most of the drugs (21/26, 81%) were given in a fixed dose independent of patient weight. BMI was an exclusion criterion in 3 out of 495 trials. Patients with diabetes, the leading comorbidity of obesity, were excluded in 67/495 trials (13.5%). Distribution of patients according to BMI was mentioned in 8% of the manuscripts, subgroup analysis was performed in 2 trials. No other measures of adiposity/body composition were mentioned in any of the trials. Retrospective analyses on the impact of BMI were performed in 6 trials.
CONCLUSIONS
Patient adiposity is hardly considered as most novel drug treatments are given in a fixed dose. BMI is generally not reported in recent trials and few secondary analyses are performed. Given the prevalence of patients with obesity and the impact obesity can have on pharmacokinetics and cancer biology, more attention should be given by investigators and study sponsors to reporting patient's BMI and evaluating its impact on treatment efficacy and toxicity.
Topics: Humans; Body Mass Index; Breast Neoplasms; Female; Obesity; Clinical Trials as Topic; Antineoplastic Agents; Treatment Outcome
PubMed: 38778365
DOI: 10.1186/s13058-024-01832-7 -
Journal of Controlled Release :... Jul 2024In situ gelling systems represent a burgeoning paradigm in ocular drug administration, addressing intrinsic challenges posed by extant ocular formulations, such as... (Review)
Review
In situ gelling systems represent a burgeoning paradigm in ocular drug administration, addressing intrinsic challenges posed by extant ocular formulations, such as compromised bioavailability and constraints in traversing the corneal barrier. This systematic review endeavours to comprehensively examine the contemporary landscape of research in this domain, focusing on the nuanced capabilities of in situ gelling systems to optimize drug delivery and enhance therapeutic outcomes, without much technological complexity. Employing a meticulous search strategy across diverse databases for publications and patents spanning the years 2015 to 2023 a total of 26 research papers and 14 patents meeting stringent inclusion criteria were identified. Synthesizing the collective insights derived from these investigations, it becomes evident that in situ gelling systems confer an ability to protract the residence time of formulations or active pharmaceutical ingredients (APIs) within the ocular milieu. This sustained presence engenders extended drug release kinetics, thereby fostering improved patient compliance and mitigating the proclivity for side effects attendant to frequent dosing. These salutary effects extend to diminished systemic drug absorption, augmented ocular bioavailability, and the prospect of reduced dosing frequencies, thereby amplifying patient adherence to therapeutic regimens. Intriguingly, the protective attributes of in situ gelling systems extend to the establishment of an ocular surface barrier, thereby abating the susceptibility to infections and inflammatory responses. In summation, this review underscores the auspicious potential of in situ gelling systems as a transformative approach to advancing ocular drug delivery, warranting sustained research endeavours and developmental initiatives for the betterment of global patient outcomes.
Topics: Humans; Drug Delivery Systems; Administration, Ophthalmic; Gels; Animals; Biological Availability; Eye; Pharmaceutical Preparations; Ophthalmic Solutions
PubMed: 38768662
DOI: 10.1016/j.jconrel.2024.05.031 -
Food Research International (Ottawa,... Jul 2024Vitamins are responsible for providing biological properties to the human body; however, their instability under certain environmental conditions limits their... (Meta-Analysis)
Meta-Analysis Review
Vitamins are responsible for providing biological properties to the human body; however, their instability under certain environmental conditions limits their utilization in the food industry. The objective was to conduct a systematic review on the use of biopolymers and lipid bases in microencapsulation processes, assessing their impact on the stability, controlled release, and viability of fortified foods with microencapsulated vitamins. The literature search was conducted between the years 2013-2023, gathering information from databases such as Scopus, PubMed, Web of Science and publishers including Taylor & Francis, Elsevier, Springer and MDPI; a total of 49 articles were compiled The results were classified according to the microencapsulation method, considering the following information: core, coating material, solvent, formulation, process conditions, particle size, efficiency, yield, bioavailability, bioaccessibility, in vitro release, correlation coefficient and references. It has been evidenced that gums are the most frequently employed coatings in the protection of vitamins (14.04%), followed by alginate (10.53%), modified chitosan (9.65%), whey protein (8.77%), lipid bases (8.77%), chitosan (7.89%), modified starch (7.89%), starch (7.02%), gelatin (6.14%), maltodextrin (5.26%), zein (3.51%), pectin (2.63%) and other materials (7.89%). The factors influencing the release of vitamins include pH, modification of the coating material and crosslinking agents; additionally, it was determined that the most fitting mathematical model for release values is Weibull, followed by Zero Order, Higuchi and Korsmeyer-Peppas; finally, foods commonly fortified with microencapsulated vitamins were described, with yogurt, bakery products and gummy candies being notable examples.
Topics: Food, Fortified; Vitamins; Drug Compounding; Chitosan; Biological Availability; Humans; Biopolymers; Alginates; Whey Proteins
PubMed: 38763670
DOI: 10.1016/j.foodres.2024.114420 -
Contraception May 2024To summarize and update information regarding drug-drug interactions (DDIs) between antiretrovirals (ARVs) and hormonal contraceptives (HCs). (Review)
Review
OBJECTIVE
To summarize and update information regarding drug-drug interactions (DDIs) between antiretrovirals (ARVs) and hormonal contraceptives (HCs).
DESIGN
Systematic review METHODS: We searched seven databases for peer-reviewed publications from January 1, 2015, through December 31, 2023, including studies of women using ARVs and HCs concurrently with outcomes including therapeutic effectiveness or toxicity, pharmacokinetics (PK), or pharmacodynamics. We summarized findings and used checklists to assess evidence quality.
RESULTS
We included 49 articles, with clinical, ARV or HC PK outcomes reported by 39, 25, and 30 articles, respectively, with some articles reporting outcomes in two or more categories. Fifteen of 18 articles assessing DDIs between efavirenz and progestin implants, emergency contraception, or combined hormonal intravaginal rings found higher pregnancy rates, luteal progesterone levels suggesting ovulation, or reduced progestin PK values. Five studies documented that CYP2B6 single nucleotide polymorphisms exacerbated this DDI. One cohort detected doubled bone density loss with concomitant depot medroxyprogesterone acetate (DMPA) and tenofovir disoproxil fumarate (TDF)-containing ART use versus TDF alone. No other studies described DDIs impacting clinical outcomes. Few adverse events were attributed to ARV-HC use with none exceeding Grade 2. Evidence quality was generally moderate, with dis-similar treatment and control groups, identifying and controlling for confounding, and minimizing attrition bias in the study design being the most frequent limitations.
CONCLUSION
Most ARVs and HCs may be used safely and effectively together. TDF-DMPA DDIs warrant longer-term study on bone health and consideration of alternate combinations. For efavirenz-based ART, client counselling on relative risks, including both potential increase in pregnancy rate with concomitant efavirenz and implant use and lower pregnancy rates compared to other HCs even with concomitant efavirenz use, should continue to allow users comprehensive method choice.
PubMed: 38762199
DOI: 10.1016/j.contraception.2024.110490 -
Progress in Neuro-psychopharmacology &... Jul 2024Increasing evidence suggests that the physiological changes of pregnancy may impact pharmacokinetics of antiseizure medications (ASM), and this may affect treatment... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Increasing evidence suggests that the physiological changes of pregnancy may impact pharmacokinetics of antiseizure medications (ASM), and this may affect treatment outcomes. The aim of this study was to quantify the pregnancy impact on the ASM pharmacokinetics.
METHODS
A systematic literature search was conducted in PubMed/EMBASE in November 2022 and updated in August 2023 for studies comparing levels of ASM in the same individuals during pregnancy and in the preconception/postpartum period. Alteration ratios between the 3rd trimester and baseline were estimated. We also performed a random-effects meta-analysis calculating between-timepoint differences in mean differences (MDs) and 95% confidence intervals (95%CIs) for dose-adjusted plasma concentrations (C/D ratios). Study quality was assessed using the ClinPK guidelines.
RESULTS
A total of 65 studies investigating 15 ASMs in 674 pregnancies were included. The largest differences were reported for lamotrigine, oxcarbazepine and levetiracetam (alteration ratio 0.42, range 0.07-2.45, 0.42, range 0.08-0.82 and 0.52, range 0.04-2.77 respectively): accordingly, C/D levels were lower in the 3rd trimester for lamotrigine, levetiracetam and the main oxcarbazepine metabolite monohydroxycarbazepine (MD = -12.33 × 10, 95%CI = -16.08 to -8.58 × 10 (μg/mL)/(mg/day), p < 0.001, MD = -7.16 (μg/mL)/(mg/day), 95%CI = -9.96 to -4.36, p < 0.001, and MD = -4.87 (μg/mL)/(mg/day), 95%CI = -9.39 to -0.35, p = 0.035, respectively), but not for oxcarbazepine (MD = 1.16 × 10 (μg/mL)/(mg/day), 95%CI = -2.55 to 0.24 × 10, p = 0.10). The quality of studies was acceptable with an average rating score of 11.5.
CONCLUSIONS
Data for lamotrigine, oxcarbazepine (and monohydroxycarbazepine) and levetiracetam demonstrate major changes in pharmacokinetics during pregnancy, suggesting the importance of therapeutic drug monitoring to assist clinicians in optimizing treatment outcomes.
Topics: Humans; Pregnancy; Anticonvulsants; Female; Pregnancy Complications; Levetiracetam; Lamotrigine; Epilepsy; Oxcarbazepine
PubMed: 38762161
DOI: 10.1016/j.pnpbp.2024.111030