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MedRxiv : the Preprint Server For... Feb 2023In this review, we provide an updated assessment of available evidence on the pharmacokinetics (PK) of cannabidiol (CBD) and explore the impact of different factors on...
BACKGROUND
In this review, we provide an updated assessment of available evidence on the pharmacokinetics (PK) of cannabidiol (CBD) and explore the impact of different factors on PK outcomes.
MATERIALS AND METHODS
This systematic review and meta-regression analysis was pre-registered (PROSPERO: CRD42021269857). We systematically searched Medline, Embase, PsychInfo, and Web of Science Core Collection up to November 19, 2022. Trials of CBD in healthy adults were included if they reported at least one of the PK parameters of interest, including Tmax, Cmax, AUC0-t, AUC0-inf, and T , in serum or plasma. Studies of patient populations or CBD co-administration with other medications were excluded. The was used. Random-effects multivariable meta-regression analysis was conducted.
RESULTS
A total of 112 trial arms from 39 studies were included; 26 trial arms had a "Good" quality, 70 "Fair," and 16 "Poor." Eight arms used inhalation CBD, 29 oromucosal, 73 oral, and 2 intravenous. CBD formulations could be categorized to nanotech (n=14), oil-based (n=21), alcohol-based (n=10), water-based (n=12), Sativex (n=17), and Epidiolex (n=22). For single-dose studies, CBD doses ranged between 2-100mg in inhalation, 5-50mg in oromucosal, and 0.42-6000mg in oral administration. Sixty-six trial arms had only male participants or a higher number of males than females. The duration of the PK session was between 4h-164h. A higher CBD dose was associated with higher Cmax, AUC0-t, and AUC0-inf. Compared to oral administration, oromucosal administration was associated with lower Cmax, AUC0-t, and AUC0-inf. Fed status was associated with higher Cmax and AUC0-t when compared to the fasting status. A higher ratio of female participants was associated with lower Tmax in oral administration and higher Cmax.
CONCLUSION
As expected, CBD dose, route of administration, and diet were major determinants of CBD pharmacokinetics with oral routes providing higher bioavailability and nanotechnology formulations a faster onset. Though CBD appeared to have a faster onset and longer duration in females, more studies are required to delineate the role of biological sex. Factors that influence CBD PK have implications for medication development and appropriate dosing in clinical practice.
PubMed: 36778355
DOI: 10.1101/2023.02.01.23285341 -
OncoTargets and Therapy 2019The present standard dose of gemcitabine (Gem), a pyrimidine antimetabolite, is 1,000-1,250 mg/m, and the infusion time is 30 min. However, pharmacological studies have... (Review)
Review
BACKGROUND
The present standard dose of gemcitabine (Gem), a pyrimidine antimetabolite, is 1,000-1,250 mg/m, and the infusion time is 30 min. However, pharmacological studies have demonstrated that Gem with prolonged infusion could attain a better accumulation rate of Gem triphosphate (active metabolites of Gem), indicating that Gem with prolonged infusion is superior to 30-min infusion. Thus, this systematic review aims to provide some references for Gem administered as a prolonged infusion.
METHODS
We searched electronic databases, including PubMed, EMBASE, Cochrane Library, and CNKI, for trials. Keywords were "Gem," "prolonged infusion," and "low-dose." In addition, we used the Cochrane Handbook V5.1.0 and methodological index for non-randomized studies to evaluate the quality of randomized controlled trials (RCTs) and non-RCTs, respectively. Furthermore, Cochrane Collaboration guidelines and the PRISMA statement were adopted.
RESULTS
We systematically reviewed 19 studies (5 RCTs and 14 non-RCTs). All studies assessed the efficacy and safety of Gem administered as a prolonged low-dose infusion (P-LDI) and reported that Gem administered as P-LDI was effective and well tolerated.
CONCLUSION
Gem administered as P-LDI is effective, safe, and economical, especially suited for patients with poor performance status or without good economic condition.
PubMed: 31417283
DOI: 10.2147/OTT.S210117 -
Nutrients May 2020Histidine is an essential amino acid (EAA) in mammals, fish, and poultry. We aim to give an overview of the metabolism and physiological effects of histidine in humans...
Histidine is an essential amino acid (EAA) in mammals, fish, and poultry. We aim to give an overview of the metabolism and physiological effects of histidine in humans and different animal species through a systematic review following the guidelines of PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). In humans, dietary histidine may be associated with factors that improve metabolic syndrome and has an effect on ion absorption. In rats, histidine supplementation increases food intake. It also provides neuroprotection at an early stage and could protect against epileptic seizures. In chickens, histidine is particularly important as a limiting factor for carnosine synthesis, which has strong anti-oxidant effects. In fish, dietary histidine may be one of the most important factors in preventing cataracts. In ruminants, histidine is a limiting factor for milk protein synthesis and could be the first limiting AA for growth. In excess, histidine supplementation can be responsible for eating and memory disorders in humans and can induce growth retardation and metabolic dysfunction in most species. To conclude, the requirements for histidine, like for other EAA, have been derived from growth and AA composition in tissues and also have specific metabolic roles depending on species and dietary levels.
Topics: Animals; Chickens; Dietary Supplements; Eating; Fishes; Gastrointestinal Absorption; Histidine; Humans; Rats; Ruminants
PubMed: 32423010
DOI: 10.3390/nu12051414 -
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 -
Frontiers in Pharmacology 2020Matrine (MT) is a naturally occurring alkaloid and an bioactive component of Chinese herbs, such as and Radix . Emerging evidence suggests that MT possesses... (Review)
Review
Matrine (MT) is a naturally occurring alkaloid and an bioactive component of Chinese herbs, such as and Radix . Emerging evidence suggests that MT possesses anti-cancer, anti-inflammatory, anti-oxidant, antiviral, antimicrobial, anti-fibrotic, anti-allergic, antinociceptive, hepatoprotective, cardioprotective, and neuroprotective properties. These pharmacological properties form the foundation for its application in the treatment of various diseases, such as multiple types of cancers, hepatitis, skin diseases, allergic asthma, diabetic cardiomyopathy, pain, Alzheimer's disease (AD), Parkinson's disease (PD), and central nervous system (CNS) inflammation. However, an increasing number of published studies indicate that MT has serious adverse effects, the most obvious being liver toxicity and neurotoxicity, which are major factors limiting its clinical use. Pharmacokinetic studies have shown that MT has low oral bioavailability and short half-life . This review summarizes the latest advances in research on the pharmacology, toxicology, and pharmacokinetics of MT, with a focus on its biological properties and mechanism of action. The review provides insight into the future of research on traditional Chinese medicine.
PubMed: 33041782
DOI: 10.3389/fphar.2020.01067 -
Pharmacogenomics and Personalized... 2022In neonates, pharmacogenetics has an additional layer of complexity. This is because in addition to genetic variability in genes that code for proteins relevant to... (Review)
Review
In neonates, pharmacogenetics has an additional layer of complexity. This is because in addition to genetic variability in genes that code for proteins relevant to clinical pharmacology, there are rapidly maturational changes in these proteins. Consequently, pharmacotherapy in neonates has unique challenges. To provide a contemporary overview on pharmacogenetics in neonates, we conducted a systematic review to identify, describe and quantify the impact of pharmacogenetics on pharmacokinetics and -dynamics in neonates and infants (PROSPERO, CRD42022302029). The search was performed in Medline, Embase, Web of Science and Cochrane, and was extended by a PubMed search on the 'top 100 Medicines' (medicine + newborn/infant + pharmacogen*) prescribed to neonates. Following study selection (including data in infants, PGx related) and quality assessment (Newcastle-Ottawa scale, Joanna Briggs Institute tool), 55/789 records were retained. Retained records relate to metabolizing enzymes involved in phase I [cytochrome P450 (CYP1A2, CYP2A6, CYP2B6, CYP2C8/C9/C18, CYP2C19, CYP2D6, CYP3A5, CYP2E1)], phase II [glutathione-S-transferases, N-acetyl transferases, UDP-glucuronosyl-transferase], transporters [ATP-binding cassette transporters, organic cation transporters], or receptor/post-receptor mechanisms [opioid related receptor and post-receptor mechanisms, tumor necrosis factor, mitogen-activated protein kinase 8, vitamin binding protein diplotypes, corticotrophin-releasing hormone receptor-1, nuclear receptor subfamily-1, vitamin K epoxide reductase complex-1, and angiotensin converting enzyme variants]. Based on the available overview, we conclude that the majority of reported pharmacogenetic studies explore and extrapolate observations already described in older populations. Researchers commonly try to quantify the impact of these polymorphisms in small datasets of neonates or infants. In a next step, pharmacogenetic studies in neonatal life should go beyond confirmation of these associations and explore the impact of pharmacogenetics as a covariate limited to maturation of neonatal life (ie, fetal malformations, breastfeeding or clinical syndromes). The challenge is to identify the specific factors, genetic and non-genetic, that contribute to the best benefit/risk balance.
PubMed: 35795337
DOI: 10.2147/PGPM.S350205 -
Journal of Cancer Research and... 2023Oral malignant and potentially malignant conditions affect several people worldwide each year. The early diagnoses of these conditions play an important role in... (Meta-Analysis)
Meta-Analysis Review
Oral malignant and potentially malignant conditions affect several people worldwide each year. The early diagnoses of these conditions play an important role in prevention and recovery. Vibrational spectroscopy techniques such as Raman spectroscopy (RS) and Fourier-transform infrared (FTIR) spectroscopy are used in the early, non-invasive, label-free diagnosis of malignant and pre-malignant conditions, and are areas of active research. However, there is no conclusive evidence suggesting the translatability of these methods into clinical practice. This systematic review and meta-analysis presents pooled evidence for RS and FTIR methods in the detection of malignant and potentially malignant conditions of the oral cavity. Electronic databases were searched for published literature on RS and FTIR in the diagnosis of oral malignant and potentially malignant conditions. The pooled sensitivity, specificity, diagnostic accuracy, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), pre-test, and post-test probability were then calculated using the random-effects model. A subgroup analysis was conducted separately for RS and FTIR methods. A total of 12 studies were included (8 of RS; 4 of FTIR) as per the eligibility criteria. The pooled sensitivity and specificity of the vibrational spectroscopy methods were calculated to be 0.99 (95% confidence interval [CI]: 0.90, 1.00) and 0.94 (95% CI: 0.85, 0.98), respectively. The area under the curve (AUC) for the summary receiving operator characteristic curve was found to be 0.99 (0.98-1.00). Therefore, the results obtained in this study suggest that the RS and FTIR methods offer great potential to be used in the early diagnosis of oral malignant and pre-malignant conditions.
Topics: Humans; Spectrum Analysis, Raman; Area Under Curve; Databases, Factual; Mouth; Odds Ratio; Syndrome
PubMed: 37313896
DOI: 10.4103/jcrt.jcrt_2275_21 -
Clinical Toxicology (Philadelphia, Pa.) Dec 2014The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup was created to provide evidence and consensus-based recommendations on the use of extracorporeal treatments... (Review)
Review
CONTEXT
The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup was created to provide evidence and consensus-based recommendations on the use of extracorporeal treatments (ECTRs) in poisoning.
OBJECTIVES
To perform a systematic review and provide clinical recommendations for ECTR in carbamazepine poisoning.
METHODS
After a systematic literature search, the subgroup extracted the data and summarized the findings following a pre-determined format. The entire workgroup voted via a two-round modified Delphi method to reach a consensus on voting statements, using a RAND/UCLA Appropriateness Method to quantify disagreement. Anonymous votes were compiled, returned, and discussed in person. A second vote determined the final recommendations.
RESULTS
Seventy-four articles met inclusion criteria. Articles included case reports, case series, descriptive cohorts, pharmacokinetic studies, and in-vitro studies; two poor-quality observational studies were identified, yielding a very low quality of evidence for all recommendations. Data on 173 patients, including 6 fatalities, were reviewed. The workgroup concluded that carbamazepine is moderately dialyzable and made the following recommendations: ECTR is suggested in severe carbamazepine poisoning (2D). ECTR is recommended if multiple seizures occur and are refractory to treatment (1D), or if life-threatening dysrhythmias occur (1D). ECTR is suggested if prolonged coma or respiratory depression requiring mechanical ventilation are present (2D) or if significant toxicity persists, particularly when carbamazepine concentrations rise or remain elevated, despite using multiple-dose activated charcoal (MDAC) and supportive measures (2D). ECTR should be continued until clinical improvement is apparent (1D) or the serum carbamazepine concentration is below 10 mg/L (42 the μ in μmol/L looks weird.) (2D). Intermittent hemodialysis is the preferred ECTR (1D), but both intermittent hemoperfusion (1D) or continuous renal replacement therapies (3D) are alternatives if hemodialysis is not available. MDAC therapy should be continued during ECTR (1D).
CONCLUSION
Despite the low quality of the available clinical evidence and the high protein binding capacity of carbamazepine, the workgroup suggested extracorporeal removal in cases of severe carbamazepine poisoning.
Topics: Adolescent; Adult; Anticonvulsants; Carbamazepine; Child; Child, Preschool; Consensus; Delphi Technique; Drug Overdose; Evidence-Based Medicine; Female; Hemoperfusion; Humans; Infant; Male; Middle Aged; Renal Dialysis; Severity of Illness Index; Treatment Outcome; Young Adult
PubMed: 25355482
DOI: 10.3109/15563650.2014.973572 -
JPMA. the Journal of the Pakistan... Mar 2023To evaluate and compare the pharmacokinetic parameters, especially bioavailability, of annatto-based tocotrienol with palm tocotrienol-rich fraction in healthy human...
OBJECTIVE
To evaluate and compare the pharmacokinetic parameters, especially bioavailability, of annatto-based tocotrienol with palm tocotrienol-rich fraction in healthy human volunteers for better therapeutic outcome.
METHODS
The systematic review was conducted between April and August 2021 in accordance with the Preferred Reporting Items for Systematic Review and Meta Analysis guidelines, and comprised search on PubMed, Google Scholar, Pakmedinet and Google search engines for open-label or double-blind randomised controlled trials involving healthy human volunteers published till January 2021. Key words used included annatto-based tocotrienol, palm tocotrienol-rich fraction, absorption and bioavailability. Boolean operators were also used, like tocotrienol AND bioavailability, annatto tocotrienol AND pharmacokinetics.
RESULTS
Of the 230 articles identified, 50(21.7%) articles met the eligibility criteria. Of them, 7(14%) were selected for data extraction and detailed analysis. Pharmacokinetic parameters of annatto-based tocotrienol were better than palm-derived tocotrienol. Oral administration of all the isomers of annatto-based tocotrienols resulted in dose-dependent increase in area under curve and plasma levels. Amongst all the isomers of annatto-based and palm-derived tocotrienol, delta isomer of annatto-based tocotrienol had the highest bioavailability with area under curve 7450±89 ng/ml, time to reach peak plasma levels 4 hours, maximum plasma concentration 1591±43 ng/nl and elimination half-life 2. 68 ±0.29 hrs. Pharmacokinetic parameters of delta isomer of annatto-based tocotrienol was greater than palm tocotrienol-rich fraction.
CONCLUSIONS
Bioavailability of annatto-based tocotrienol was better than that of palm-derived tocotrienol-rich fraction. Delta isomer of annatto-based tocotrienol had the highest bioavailability amongst all isomers of tocotrienol.
Topics: Humans; Tocotrienols; Biological Availability; Health Status; Randomized Controlled Trials as Topic
PubMed: 36932765
DOI: 10.47391/JPMA.6008 -
Journal of the American Heart... Oct 2017Time in the therapeutic range (TTR) is associated with the effectiveness and safety of vitamin K antagonist (VKA) therapy. To optimize prescribing of VKA, we aimed to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Time in the therapeutic range (TTR) is associated with the effectiveness and safety of vitamin K antagonist (VKA) therapy. To optimize prescribing of VKA, we aimed to develop and validate a prediction model for TTR in older adults taking VKA for nonvalvular atrial fibrillation and venous thromboembolism.
METHODS AND RESULTS
The study cohort comprised patients aged ≥65 years who were taking VKA for atrial fibrillation or venous thromboembolism and who were identified in the 2 US electronic health record databases linked with Medicare claims data from 2007 through 2014. With the predictors identified from a systematic review and clinical knowledge, we built a prediction model for TTR, using one electronic health record system as the training set and the other as the validation set. We compared the performance of the new models to that of a published prediction score for TTR, SAMe-TTR. Based on 1663 patients in the training set and 1181 in the validation set, our optimized score included 42 variables and the simplified model included 7 variables, abbreviated as PROSPER (Pneumonia, Renal dysfunction, Oozing blood [prior bleeding], Staying in hospital ≥7 days, Pain medication use, no Enhanced [structured] anticoagulation services, Rx for antibiotics). The PROSPER score outperformed SAMe-TTR when predicting both TTR ≥70% (area under the receiver operating characteristic curve 0.67 versus 0.55) and the thromboembolic and bleeding outcomes (area under the receiver operating characteristic curve 0.62 versus 0.52).
CONCLUSIONS
Our geriatric TTR score can be used as a clinical decision aid to select appropriate candidates to receive VKA therapy and as a research tool to address confounding and treatment effect heterogeneity by anticoagulation quality.
Topics: Age Factors; Aged; Analgesics; Anti-Bacterial Agents; Anticoagulants; Area Under Curve; Atrial Fibrillation; Blood Coagulation; Clinical Decision-Making; Databases, Factual; Decision Support Techniques; Drug Monitoring; Electronic Health Records; Female; Hemorrhage; Humans; International Normalized Ratio; Length of Stay; Male; Patient Selection; Predictive Value of Tests; Quality Control; Quality Indicators, Health Care; ROC Curve; Reproducibility of Results; Risk Factors; Time Factors; Treatment Outcome; Venous Thromboembolism
PubMed: 28982676
DOI: 10.1161/JAHA.117.006814