Drug metabolism and personalized therapy最新文献

{"title":"Concept of Unani Jali (detergents/cleansers) drugs and its scientific validation: scope for new opportunities in dermatological pharmacotherapeutics.","authors":"Shabnam Anjum Ara,&nbsp;Shaheen Akhlaq,&nbsp;Bilal Ahmad,&nbsp;Mohammad Fazil,&nbsp;Usama Akram,&nbsp;Merajul Haque,&nbsp;Ahmad Sayeed,&nbsp;Asim Ali Khan","doi":"10.1515/dmpt-2022-0121","DOIUrl":"https://doi.org/10.1515/dmpt-2022-0121","url":null,"abstract":"<p><strong>Objectives: </strong>The use of detergent-action drugs in traditional Unani therapeutic intervention has been a long-standing Unani medicinal practice. The key aim of the article is to provide thorough information on the novel, unexplored idea of Unani Jali (detergent/cleansers) drugs for the treatment of skin ailments, as well as to identify medicinal plants that have detergent action and correlate these findings with scientific studies that may support evidence for the drug's detergent effect.</p><p><strong>Content: </strong>The ethnobotanical classical literature of Unani medicine was investigated in order to have a comprehensive insight of Unani detergents/cleansers. Scientific studies were carried from databases including PubMed, Scopus, Science Direct, and google Scholar, among others. More than fifty exclusive plant, mineral, and animal-based detergents are found specifically for skin disorders in Unani therapy. These drugs basically evacuate impurities from the body's excretory system and and have been found to have keratolytic and debris-peeling effects, as well as the ability to maintain skin tone consistency. Unani Jali drugs have also been found to have anti-inflammatory, antibacterial, analgesic, and tonic properties, suggesting its usefulness holistically.</p><p><strong>Summary and outlook: </strong>Based on phyto constituents, prospective therapeutic response, and scientific data, this review proposes that Unani Jali drugs could be a safe and promising therapeutic option for dermatological illnesses such as vitiligo, acne, dermatitis, psoriasis, and skin sensitivity.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":"38 1","pages":"31-43"},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9537057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The efficacy and safety of dry cupping in cervical spondylosis with optimization of cup application time - a randomized clinical trial.","authors":"Ayesha Tehseen,&nbsp;Hamid Ali,&nbsp;Nazim Husain,&nbsp;Hina Kouser Varda","doi":"10.1515/dmpt-2022-0111","DOIUrl":"https://doi.org/10.1515/dmpt-2022-0111","url":null,"abstract":"<p><strong>Objectives: </strong>Dry cupping therapy (DCT) is considered beneficial in the amelioration of cervical spondylosis (CS) symptoms in Unani medicine. Therefore, the focus of this study was to ascertain the efficacy of DCT and optimal cup application time duration for CS.</p><p><strong>Methods: </strong>It was a randomized clinical trial involving 45 participants with clinically diagnosed CS. The eligible subjects were randomly categorized into three groups, each having 15 participants. Each of the three groups, i.e., A, B, and C, received DCT daily for 15 days for 8 min, 10 min, and 12 min, respectively. All the participants were evaluated at the baseline, 7th, and 15th days of the trial using the neck disability index (NDI) as well as the visual analogue scale (VAS).</p><p><strong>Results: </strong>The baseline mean ± SD of NDI and VAS scores were significantly reduced in all the three groups at the end of the trial. Although all three groups were statistically equal in terms of NDI, group-C demonstrated greater efficacy in terms of VAS.</p><p><strong>Conclusions: </strong>The per-protocol analysis showed that dry cupping effectively alleviated neck pain across all treatment groups. Although, this effect on neck disability index was statistically equal in all three groups, the 12-min protocol was more successful in reducing pain.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":"38 1","pages":"113-119"},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9169702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The investigation of the complex population-drug-drug interaction between ritonavir-boosted lopinavir and chloroquine or ivermectin using physiologically-based pharmacokinetic modeling.","authors":"Mo'tasem M Alsmadi","doi":"10.1515/dmpt-2022-0130","DOIUrl":"https://doi.org/10.1515/dmpt-2022-0130","url":null,"abstract":"<p><strong>Objectives: </strong>Therapy failure caused by complex population-drug-drug (PDDI) interactions including CYP3A4 can be predicted using mechanistic physiologically-based pharmacokinetic (PBPK) modeling. A synergy between ritonavir-boosted lopinavir (LPVr), ivermectin, and chloroquine was suggested to improve COVID-19 treatment. This work aimed to study the PDDI of the two CYP3A4 substrates (ivermectin and chloroquine) with LPVr in mild-to-moderate COVID-19 adults, geriatrics, and pregnancy populations.</p><p><strong>Methods: </strong>The PDDI of LPVr with ivermectin or chloroquine was investigated. Pearson's correlations between plasma, saliva, and lung interstitial fluid (ISF) levels were evaluated. Target site (lung epithelial lining fluid [ELF]) levels of ivermectin and chloroquine were estimated.</p><p><strong>Results: </strong>Upon LPVr coadministration, while the chloroquine plasma levels were reduced by 30, 40, and 20%, the ivermectin plasma levels were increased by a minimum of 425, 234, and 453% in adults, geriatrics, and pregnancy populations, respectively. The established correlation equations can be useful in therapeutic drug monitoring (TDM) and dosing regimen optimization.</p><p><strong>Conclusions: </strong>Neither chloroquine nor ivermectin reached therapeutic ELF levels in the presence of LPVr despite reaching toxic ivermectin plasma levels. PBPK modeling, guided with TDM in saliva, can be advantageous to evaluate the probability of reaching therapeutic ELF levels in the presence of PDDI, especially in home-treated patients.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":"38 1","pages":"87-105"},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9222472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Post-treatment symptomatic improvement of the eastern Indian ADHD probands is influenced by <i>CYP2D6</i> genetic variations.","authors":"Mahasweta Chatterjee,&nbsp;Sharmistha Saha,&nbsp;Subhamita Maitra,&nbsp;Anirban Ray,&nbsp;Swagata Sinha,&nbsp;Kanchan Mukhopadhyay","doi":"10.1515/dmpt-2022-0120","DOIUrl":"https://doi.org/10.1515/dmpt-2022-0120","url":null,"abstract":"<p><strong>Objectives: </strong>Symptomatic remediation from attention deficit hyperactivity disorder (ADHD)-associated traits is achieved by treatment with methylphenidate (MPH)/atomoxetine (ATX). We have analyzed the association of functional <i>CYP2D6</i> variations, rs1065852, rs3892097, rs1135840, and rs1058164, with ADHD in the Indian subjects.</p><p><strong>Methods: </strong>Subjects were recruited following the Diagnostic and Statistical Manual for Mental Disorders. Trait scores were obtained from the Conner's Parents Rating Scale-Revised. After obtaining informed consent, blood was collected for DNA isolation, and genotyping was performed by PCR or TaqMan-based methods. Probands were treated with MPH or ATX based on age, symptoms, and drug availability. Treatment outcome was assessed using a structured questionnaire. Data obtained was analyzed to identify the association of <i>CYP2D6</i> variations and the <i>SLC6A3</i> rs28363170 with the treatment outcome.</p><p><strong>Results: </strong>The frequency of rs1135840 \"G\" and rs1065852 \"G\" was higher in the male ADHD probands. Bias in parental transmission (p=0.007) and association with higher trait scores were observed for rs1065852 \"A\". Independent influence of rs1065852 on ADHD was also observed. Probands carrying rs1065852 'GG', rs1135840 'CG', and rs28363170 10R exhibited significant symptomatic improvement with MPH, while probands with rs1135840 'CC' and rs28363170 9R showed improvement after ATX treatment.</p><p><strong>Conclusions: </strong>ADHD probands having specific <i>CYP2D6</i> genetic variations respond differentially to pharmaceutical intervention.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":"38 1","pages":"45-56"},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9177361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frontmatter","authors":"","doi":"10.1515/dmpt-2023-frontmatter1","DOIUrl":"https://doi.org/10.1515/dmpt-2023-frontmatter1","url":null,"abstract":"","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":"33 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135075509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Type 2 diabetes: an exploratory genetic association analysis of selected metabolizing enzymes and transporters and effects on cardiovascular and renal biomarkers.","authors":"Russell W Fankhouser,&nbsp;Derek E Murrell,&nbsp;Yaa Y Anane,&nbsp;David L Hurley,&nbsp;Hadii M Mamudu,&nbsp;Sam Harirforoosh","doi":"10.1515/dmpt-2021-0135","DOIUrl":"https://doi.org/10.1515/dmpt-2021-0135","url":null,"abstract":"<p><strong>Objectives: </strong>This study sought to identify potential pharmacogenetic associations of selected enzymes and transporters with type 2 diabetes (T2D). In addition, pharmacogenomic profiles, concentrations of asymmetric dimethylarginine (ADMA) or kidney injury molecule-1 (KIM-1), and several covariates were investigated.</p><p><strong>Methods: </strong>Whole blood was collected from 63 patients, with 32 individuals with T2D. A pharmacogenomic panel was used to assay genetic profiles, and biomarker ELISAs were run to determine subject concentrations of ADMA and KIM-1. Additive genetic modeling with multiple linear and logistic regressions were performed to discover potential SNPs-outcome associations using PLINK.</p><p><strong>Results: </strong>Ten SNPs were found to be significant (p<0.05) depending on the inclusion or exclusion of covariates. Of these, four were found in association with the presence of T2D, rs2231142, rs1801280, rs1799929, and rs1801265 depending on covariate inclusion or exclusion. Regarding ADMA, one SNP was found to be significant without covariates, rs1048943. Five SNPs were identified in association with KIM-1 and T2D in the presence of covariates, rs12208357, rs34059508, rs1058930, rs1902023, and rs3745274. Biomarker concentrations were not significantly different in the presence of T2D.</p><p><strong>Conclusions: </strong>This exploratory study found several SNPs related to T2D; further research is required to validate and understand these relationships.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":"37 4","pages":"375-382"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10364105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of nonadherence on phenobarbital concentrations and recommendations on the replacement dose using Monte Carlo simulation.","authors":"Janthima Methaneethorn","doi":"10.1515/dmpt-2022-0104","DOIUrl":"https://doi.org/10.1515/dmpt-2022-0104","url":null,"abstract":"<p><strong>Objectives: </strong>To determine the impacts of missed phenobarbital (PB) doses on its pharmacokinetics and to investigate the appropriate replacement dosing scheme for various PB missed dose scenarios.</p><p><strong>Methods: </strong>Monte Carlo simulations were performed using parameters from the selected population pharmacokinetic study. The impacts of missed PB dose and the proper replacement dosing scheme were assessed based on the percent deviation of simulated concentrations outside the reference range from the full adherence scenario.</p><p><strong>Results: </strong>The impact of missed PB dose on its concentrations depended on the daily dose. The replacement with a respective regular dose and one and a half regular dose was appropriate for the one and two missed doses scenarios for patients receiving PB monotherapy. For patients receiving PB with valproic acid or phenytoin, the same replacement scheme was still appropriate. The results also indicated that weight did not influence the proper replacement dosing scheme.</p><p><strong>Conclusions: </strong>The impacts of missed PB doses on its pharmacokinetics were identified and the proper replacement dosing schemes for different missed dose scenarios were proposed. These schemes should be implemented based on the clinician's justification of the patient's seizure control.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":"37 4","pages":"337-346"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10336675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenylalanine monooxygenase and the 'sulfoxidation polymorphism'; the salient points.","authors":"Glyn B Steventon,&nbsp;Stephen C Mitchell","doi":"10.1515/dmpt-2021-0233","DOIUrl":"https://doi.org/10.1515/dmpt-2021-0233","url":null,"abstract":"","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":"37 4","pages":"393-395"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10356060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"No association between LDL receptor and <i>CETP</i> genetic variants and atorvastatin response in Jordanian hyperlipidemic patients.","authors":"Malek Zihlif,&nbsp;Suhad Otoum,&nbsp;Mohammad Al Shhab,&nbsp;Zaid Almadani,&nbsp;Monther Momani,&nbsp;Hussam Alhawari,&nbsp;Esraa Jibrini,&nbsp;Yazun Jarrar,&nbsp;Hamzeh Al-Ameer,&nbsp;Amer Imraish","doi":"10.1515/dmpt-2021-0177","DOIUrl":"https://doi.org/10.1515/dmpt-2021-0177","url":null,"abstract":"<p><strong>Objectives: </strong>Atorvastatin is commonly used medication to achieve low levels of low-density lipoproteins (LDL). Cholesteryl ester transfer protein (<i>CETP</i>) and LDL receptor (<i>LDLR</i>) genetic variants can affect the cholesterol transport and hence may affect on atorvastatin response. This study aimed to investigate the influence of LDLR <i>AvaII</i>, <i>CETP TaqIb,</i> and <i>Rs1532624</i> on the efficacy of 20 mg atorvastatin among Jordanian hyperlipidemic patients.</p><p><strong>Methods: </strong>One hundred and 50 blood samples were collected from hyperlipidemic patients in the University of Jordan Hospital. Polymerase chain reaction-restriction fragment length polymorphism was used for genotyping of <i>LDLR AvaII</i> and <i>CETP TaqIb</i> genetic variants. The genotyping of <i>CETP Rs1532624</i> variant was done by Sanger DNA-Sequencing.</p><p><strong>Results: </strong>LDLR <i>AvaII</i> and <i>CETP TaqIb</i> and <i>Rs1532624</i> variants showed a significant (p value < 0.05) association with the baseline of the LDL at the time of diagnoses. On the other hand, none of the tested genetic variants showed a significant (p value>0.05) association with LDL reduction after atorvastatin therapy.</p><p><strong>Conclusions: </strong>Results demonstrated a significant association between the <i>LDLR AvaII</i> and <i>CETP TaqIb,</i> and <i>Rs1532624</i> genetic variants with the LDL baseline level. However, the atorvastatin therapy among hyperlipidemic patients of Jordanian origin was not affected by any of the tested variants.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":"37 4","pages":"369-374"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10364388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>SLCO1B1</i> c.521T>C gene polymorphism decreases hypoglycemia risk in sulfonylurea-treated type 2 diabetic patients.","authors":"Georgia Ragia,&nbsp;Natalia Atzemian,&nbsp;Anthi Maslarinou,&nbsp;Vangelis G Manolopoulos","doi":"10.1515/dmpt-2022-0131","DOIUrl":"https://doi.org/10.1515/dmpt-2022-0131","url":null,"abstract":"<p><strong>Objectives: </strong>Pharmacogenomics can explain some of the heterogeneity of sulfonylurea (SU)-related hypoglycemia risk. Recently, a role of OATP1B1, encoded by <i>SLCO1B1</i> gene, on SU liver transport prior of metabolism has been uncovered. The aim of the present study was to explore the potential association of <i>SLCO1B1</i> c.521T>C polymorphism, leading to reduced OATP1B1 function, with SU-related hypoglycemia risk.</p><p><strong>Methods: </strong>Study cohort consists of 176 type 2 diabetes patients treated with the SUs glimepiride or gliclazide. 92 patients reported SU-related hypoglycemia, while 84 patients had never experienced a hypoglycemic event. Patients were previously genotyped for <i>CYP2C9</i> *2 and *3 variant alleles that lead to decreased enzyme activity of the SU metabolizing enzyme CYP2C9 and have been associated with increased SU-related hypoglycemia risk. <i>SLCO1B1</i> c.521T>C polymorphism was genotyped by use of PCR-RFLP analysis.</p><p><strong>Results: </strong><i>SLCO1B1</i> c.521TC genotype frequency was significantly lower in hypoglycemic cases than non-hypoglycemic controls (15.2% vs. 32.1%, p=0.008). In an adjusted model, c.521TC genotype significantly reduced the risk of hypoglycemia (OR 0.371; 95% C.I. 0.167-0.822; p=0.015). In CYP2C9 intermediate metabolizers (n=54) c.521TC genotype frequency was significantly decreased in cases compared to controls (3 out of 36 cases, 8.3% vs. 7 out of 18 controls, 38.9%, p=0.012). A similar albeit not significant difference of <i>SLCO1B1</i> c.521TC genotype was present in CYP2C9 extensive metabolizers (n=120) (18.2% in cases vs. 30.8% in controls, p=0.113).</p><p><strong>Conclusions: </strong>We have found a protective effect of <i>SLCO1B1</i> c.521C variant on SU-related hypoglycemia risk both independently and in interaction with CYP2C9 phenotypes. Our results suggest a possible linkage of <i>SLCO1B1</i> c.521T>C polymorphism with variants in other genes impairing OATPs expressed in pancreatic islets that could interfere with SU tissue distribution.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":"37 4","pages":"347-352"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10356069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}