-
Frontiers in Pharmacology 2022The decision of vancomycin dosage for central nervous system (CNS) infections is still a challenge because its bactericidal nature in cerebrospinal fluid (CSF) has not... (Review)
Review
The decision of vancomycin dosage for central nervous system (CNS) infections is still a challenge because its bactericidal nature in cerebrospinal fluid (CSF) has not been confirmed by human studies. This study systematically reviewed the literatures on vancomycin in patients with meningitis, ventriculitis, and CNS device-associated infections, to assess efficacy, safety, and pharmacokinetics to better serve as a practical reference. Medline, Embase, and Cochrane Library were searched using terms vancomycin, Glycopeptides, meningitis, and central nervous system infections. Data were extracted including characteristics of participants, causative organism(s), administration, dosage, etc., The clinical response, microbiological response, adverse events and pharmacokinetic parameters were analyzed. Nineteen articles were included. Indications for vancomycin included meningitis, ventriculitis, and intracranial device infections. No serious adverse effects of intravenous (IV) and intraventricular (IVT) vancomycin have been reported. Dosages of IV and IVT vancomycin ranged from 1000-3000 mg/day and 2-20 mg/day. Duration of IV and IVT vancomycin therapy most commonly ranged from 3-27 days and 2-21 days. Therapeutic drug monitoring was conducted in 14 studies. Vancomycin levels in CSF in patients using IV and IVT vancomycin were varied widely from 0.06 to 22.3 mg/L and 2.5-292.9 mg/L. No clear relationships were found between vancomycin CSF levels and efficacy or toxicity. Using vancomycin to treat CNS infections appears effective and safe based on current evidence. However, the optimal regimens are still unclear. Higher quality clinical trials are required to explore the vancomycin disposition within CNS.
PubMed: 36467047
DOI: 10.3389/fphar.2022.1056148 -
Obesity Surgery Sep 2022Currently, there is no consensus on whether a standard 2-g prophylactic cefazolin dose provides sufficient antimicrobial coverage in obese surgical patients. This... (Review)
Review
Currently, there is no consensus on whether a standard 2-g prophylactic cefazolin dose provides sufficient antimicrobial coverage in obese surgical patients. This systematic review analysed both outcome and pharmacokinetic studies, aiming to determine the appropriate cefazolin dose. A systematic search was conducted using 4 databases. In total, 3 outcome and 15 pharmacokinetic studies met the inclusion criteria. All 3 outcome studies concluded that there is no need for increased dose. Also, 9 pharmacokinetic studies reached this conclusion; however, 6 pharmacokinetic studies recommended that 2-g dose is insufficient to achieve adequate plasma or tissue concentrations. The stronger body of evidence supports that 2-g dose of cefazolin is sufficient for surgery lasting up to 4 h; however, large-scale outcome studies are needed to confirm this evidence.
Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Cefazolin; Humans; Obesity; Obesity, Morbid; Surgical Wound Infection
PubMed: 35809198
DOI: 10.1007/s11695-022-06196-5 -
British Journal of Clinical Pharmacology Jul 2022Rifampicin has become an essential component as the first-line therapy for pulmonary tuberculosis (PTB). Several population pharmacokinetic (PK) studies on rifampicin in... (Review)
Review
AIMS
Rifampicin has become an essential component as the first-line therapy for pulmonary tuberculosis (PTB). Several population pharmacokinetic (PK) studies on rifampicin in adult and child populations have been studied previously, therefore the aims of the systematic review were (i) to summarize the relevant published studies and significant covariates that influence the PK of rifampicin across different populations, and (ii) to identify any knowledge gap that requires additional research in the future.
METHODS
A total of 121 relevant population PK articles were systematically identified using PubMed and Scopus from inception to October 2021. Review articles, in-vitro and physiological methods, animal studies and noncompartmental analysis were excluded.
RESULTS
Nineteen studies, of which 16 involved adults, two involved children, and one involved both adults and children, were included in the review. The structural model of rifampicin can be described as one compartment with a transient compartment absorption model and first-order elimination in most of the studies. Pharmaceutical formulation, body weight, gender, pregnancy status, diabetes and nutritional supplementation were found to be the significant covariates that affect the PK parameters. External validation of the developed PK model was only conducted in two studies.
CONCLUSIONS
The source of variability for PK parameters of rifampicin remains inconsistent and poorly understood even though there were many potential covariates investigated in the selected studies. Exploring other possible factors and implementing a strict sampling strategy by considering the induction effects might uncover precise and reliable information. Furthermore, external validation should be frequently conducted to produce better predictability of model performance.
Topics: Animals; Body Weight; Female; Humans; Models, Biological; Pregnancy; Rifampin
PubMed: 35253251
DOI: 10.1111/bcp.15298 -
Pharmaceutics May 2023Loop diuretics and antibiotics are commonly co-prescribed across many clinical care settings. Loop diuretics may alter antibiotic pharmacokinetics (PK) via several... (Review)
Review
Loop diuretics and antibiotics are commonly co-prescribed across many clinical care settings. Loop diuretics may alter antibiotic pharmacokinetics (PK) via several potential drug interactions. A systematic review of the literature was performed to investigate the impact of loop diuretics on antibiotic PK. The primary outcome metric was the ratio of means (ROM) of antibiotic PK parameters such as area under the curve (AUC) and volume of distribution (V) on and off loop diuretics. Twelve crossover studies were amenable for metanalysis. Coadministration of diuretics was associated with a mean 17% increase in plasma antibiotic AUC (ROM 1.17, 95% CI 1.09-1.25, I = 0%) and a mean decrease in antibiotic V by 11% (ROM 0.89, 95% CI 0.81-0.97, I = 0%). However, the half-life was not significantly different (ROM 1.06, 95% CI 0.99-1.13, I = 26%). The remaining 13 observational and population PK studies were heterogeneous in design and population, as well as prone to bias. No large trends were collectively observed in these studies. There is currently not enough evidence to support antibiotic dosing changes based on the presence or absence of loop diuretics alone. Further studies designed and powered to detect the effect of loop diuretics on antibiotic PK are warranted in applicable patient populations.
PubMed: 37242653
DOI: 10.3390/pharmaceutics15051411 -
Cancer Treatment Reviews Apr 2023The anti-tumor activity of WEE1 inhibitors (WEE1i) in gynecological malignancies has recently been demonstrated in clinical trials and its rationale is based on... (Review)
Review
INTRODUCTION
The anti-tumor activity of WEE1 inhibitors (WEE1i) in gynecological malignancies has recently been demonstrated in clinical trials and its rationale is based on biological/molecular features of gynecological cancers. With this systematic review, we aim to outline the clinical development and current evidence regarding the efficacy and safety of these targeted agents in in this patient group.
METHODS
Systematic literature review of trials including patients with gynecological cancers treated with a WEE1i. The primary objective was to summarize the efficacy of WEE1i in gynecological malignancies regarding objective response rate (ORR), clinical benefit rate (CBR), overall survival (OS) and progression-free survival (PFS). Secondary objectives included toxicity profile, Maximum Tolerated Dose (MTD), pharmacokinetics, drug-drug interactions and exploratory objectives such as biomarkers for response.
RESULTS
26 records were included for data extraction. Almost all trials used the first-in-class WEE1i adavosertib; one conference abstract reported about Zn-c3. The majority of the trials included diverse solid tumors (n = 16). Six records reported efficacy results of WEE1i in gynecological malignancies (n = 6). Objective response rates of adavosertib monotherapy or in combination with chemotherapy ranged between 23% and 43% in these trials. Median PFS ranged from 3.0 to 9.9 months. The most common adverse events were bone marrow suppression, gastrointestinal toxicities and fatigue. Mainly alterations in cell cycle regulator genes TP53 and CCNE1 were potential predictors of response.
CONCLUSION
This report summarizes encouraging clinical development of WEE1i in gynecological cancers and considers its application in future studies. Biomarker-driven patient selection might be essential to increase the response rates.
Topics: Female; Humans; Genital Neoplasms, Female; Antineoplastic Agents; Protein-Tyrosine Kinases; Cell Cycle Proteins
PubMed: 36893690
DOI: 10.1016/j.ctrv.2023.102531 -
Biomedicines Sep 2023The clinical response to classical immunosuppressant drugs (cIMDs) is highly variable among individuals. We performed a systematic review of published evidence... (Review)
Review
The clinical response to classical immunosuppressant drugs (cIMDs) is highly variable among individuals. We performed a systematic review of published evidence supporting the hypothesis that gut microorganisms may contribute to this variability by affecting cIMD pharmacokinetics, efficacy or tolerability. The evidence that these drugs affect the composition of intestinal microbiota was also reviewed. The PubMed and Scopus databases were searched using specific keywords without limits of species (human or animal) or time from publication. One thousand and fifty five published papers were retrieved in the initial database search. After screening, 50 papers were selected to be reviewed. Potential effects on cIMD pharmacokinetics, efficacy or tolerability were observed in 17/20 papers evaluating this issue, in particular with tacrolimus, cyclosporine, mycophenolic acid and corticosteroids, whereas evidence was missing for everolimus and sirolimus. Only one of the papers investigating the effect of cIMDs on the gut microbiota reported negative results while all the others showed significant changes in the relative abundance of specific intestinal bacteria. However, no unique pattern of microbiota modification was observed across the different studies. In conclusion, the available evidence supports the hypothesis that intestinal microbiota could contribute to the variability in the response to some cIMDs, whereas data are still missing for others.
PubMed: 37761003
DOI: 10.3390/biomedicines11092562 -
Pharmaceutics Feb 2022Although several studies have revealed the association between rosuvastatin pharmacokinetics and the ABCG2 421C>A (rs2231142) polymorphism, most studies were conducted... (Review)
Review
Although several studies have revealed the association between rosuvastatin pharmacokinetics and the ABCG2 421C>A (rs2231142) polymorphism, most studies were conducted with small sample sizes, making it challenging to apply the findings clinically. Therefore, the purpose of this study is to perform a meta-analysis of the relationship between the ABCG2 421C>A polymorphism and rosuvastatin pharmacokinetics. We searched three electronic databases, EMBASE, PubMed, and Web of Science, using search terms related to ABCG2 gene polymorphisms and rosuvastatin. In addition, we reviewed studies published before 12 August 2021, to examine the relationship between the ABCG2 421C>A polymorphism and rosuvastatin pharmacokinetics. To examine the magnitude of the association, the log geometric mean difference (lnGM) and 95% confidence intervals (CIs) were calculated and interpreted as the antilogarithm of a natural logarithm (elnGM). The meta-analysis was performed using Review Manager (version 5.4) and R Studio (version 4.0.2). Subgroup analysis was performed according to race and the types of mean values. Among the 318 identified studies, a total of 8 studies involving 423 patients is included in this meta-analysis. The A allele carriers of ABCG2 421C>A showed 1.5 times higher in both AUC0-∞ (lnGM = 0.43; 95% CI = 0.35−0.50; p < 0.00001) and Cmax (lnGM = 0.42; 95% CI = 0.33−0.51; p < 0.00001) than non-carriers, while there was no significant difference in Tmax and half-life. There was no significance in the pharmacokinetic parameters of the subgroups using either ethnicity or mean values. This meta-analysis demonstrates that subjects carrying the A allele of ABCG2 421C>A show significantly increased AUC0-∞ and Cmax values compared to subjects with the CC genotype. Therefore, information about ABCG2 genotypes might be useful for individualized rosuvastatin therapy.
PubMed: 35335877
DOI: 10.3390/pharmaceutics14030501 -
Biomedicine & Pharmacotherapy =... Sep 2023Neurodegenerative diseases (NDDs) encompass a range of conditions that involve progressive deterioration and dysfunction of the nervous system. Some of the common NDDs... (Review)
Review
Neurodegenerative diseases (NDDs) encompass a range of conditions that involve progressive deterioration and dysfunction of the nervous system. Some of the common NDDs include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). Although significant progress has been made in understanding the pathological mechanisms of NDDs in recent years, the development of targeted and effective drugs for their treatment remains challenging. Kaempferol is a flavonoid whose derivatives include kaempferol-O-rhamnoside, 3-O-β-rutinoside/6-hydroxykaempferol 3,6-di-O-β-d-glucoside, and kaempferide. Emerging studies have suggested that kaempferol and its derivatives possess neuroprotective properties and may have potential therapeutic benefits in NDDs. Here, we aimed to provide a theoretical basis for the use of kaempferol and its derivatives in the clinical treatment of NDDs. We systematically reviewed the literature in the PubMed, Web of Science, and Science Direct databases until June 2022 using the search terms "kaempferol," "kaempferol derivatives," "NDDs," "pharmacokinetics," and "biosynthesis" according to the reporting items for systematic review (PRISMA) standard. Based on combined results of in vivo and in vitro studies, we summarize the basic mechanisms and targets of kaempferol and its derivatives in the management of AD, PD, HD, and ALS. Kaempferol and its derivatives exert a neuroprotective role mainly by preventing the deposition of amyloid fibrils (such as Aβ, tau, and α-synuclein), inhibiting microglia activation, reducing the release of inflammatory factors, restoring the mitochondrial membrane to prevent oxidative stress, protecting the blood-brain barrier, and inhibiting specific enzyme activities (such as cholinesterase). Kaempferol and its derivatives are promising natural neuroprotective agents. By determining their pharmacological mechanism, kaempferol and its derivatives may be new candidate drugs for the treatment of NDDs.
Topics: Humans; Neurodegenerative Diseases; Neuroprotective Agents; Amyotrophic Lateral Sclerosis; Kaempferols; Alzheimer Disease; Parkinson Disease; Huntington Disease
PubMed: 37494786
DOI: 10.1016/j.biopha.2023.115215 -
RSC Advances Mar 2021Recent advances in nanotechnology have contributed tremendously to the development and revolutionizing of drug delivery systems in the field of nanomedicine. In... (Review)
Review
Recent advances in nanotechnology have contributed tremendously to the development and revolutionizing of drug delivery systems in the field of nanomedicine. In particular, targeting nanoparticles based on biodegradable poly(lactic--glycolic acid) (PLGA) polymers have gained much interest. However, PLGA nanoparticles remain of concern for their effectiveness against cancer cells and their toxicity to normal cells. The aim of this systematic review is to identify a promising targeting PLGA nanoformulation based on the comparison study of their cytotoxicity potency in different cell lines. A literature search was conducted through the databases of Google Scholar, PubMed, ScienceDirect, Scopus and SpringerLink. The sources studied were published between 2009 and 2019, and a variety of keywords were utilized. In total, 81 manuscripts that met the inclusion and exclusion criteria were selected for analysis based on their cytotoxicity, size, zeta potential, year of publication, type of ligand, active compounds and cell line used. The half maximal inhibitory concentration (IC) for cytotoxicity was the main measurement in this data extraction, and the SI units were standardized to μg mL for a better view of comparison. This systematic review also identified that cytotoxicity potency was inversely proportional to nanoparticle size. The PLGA nanoparticles predominantly exhibited a size of less than 300 nm and absolute zeta potential ∼20 mV. In conclusion, more comprehensive and critical appraisals of pharmacokinetic, pharmacokinetic, toxicokinetic, and tests are required for the investigation of the full value of targeting PLGA nanoparticles for cancer treatment.
PubMed: 35423427
DOI: 10.1039/d1ra00074h -
The Journal of Pediatric Pharmacology... 2021To evaluate the pharmacokinetics and pharmacodynamics, dosing, efficacy, and safety of ketorolac in postoperative patients younger than 6 months of age. (Review)
Review
OBJECTIVE
To evaluate the pharmacokinetics and pharmacodynamics, dosing, efficacy, and safety of ketorolac in postoperative patients younger than 6 months of age.
METHODS
PubMed (1988-July 2020), Medline (1946-July 2020), and EBSCO Discovery Service (1988-July 2020) were searched to identify relevant published articles using the following search terms: ketorolac, neonate, infant. English-language articles evaluating the use of ketorolac in infants younger than 6 months of age were included.
RESULTS
Eight reports that included 239 infants receiving ketorolac were included. Of the included patients, 237 were younger than 6 months of age. Ketorolac exhibits rapid elimination of the analgesia-producing S (-) isomer, elimination half-life of 0.83 hours. Most patients received 0.5 mg/kg/dose every 6 hours for 48 to 72 hours. Analgesia was demonstrated by reduced use of open-label morphine and significant lowering of Neonatal/Infant Pain Scale scores. Adverse effects were minimal when ketorolac was used in term neonates and infants without baseline renal dysfunction.
CONCLUSIONS
Randomized placebo-controlled trials of ketorolac use in this population are lacking; however, most published reports noted efficacy and safety with ketorolac in properly selected infants.
PubMed: 33833624
DOI: 10.5863/1551-6776-26.3.240