Published since December 1, 1980

Drug Metabolism and Personalized Therapy

Official journal of the European Society of Pharmacogenomics and Personalised Therapy

ISSN: 2363-8915

Editor-in-chief: Adrián Llerena

About this journal

Objective
Drug Metabolism and Personalized Therapy (DMPT) is a peer-reviewed journal, and is abstracted/indexed in relevant major Abstracting Services. It provides up-to-date research articles, reviews and opinion papers in the wide field of drug metabolism research, covering established, new and potential drugs, environmentally toxic chemicals, the mechanisms by which drugs may interact with each other and with biological systems, and the pharmacological and toxicological consequences of these interactions and drug metabolism and excretion.

Topics

drug metabolizing enzymes
pharmacogenetics and pharmacogenomics
biochemical pharmacology
molecular pathology
clinical pharmacology
pharmacokinetics and drug-drug interactions
immunopharmacology
neuropsychopharmacology

Article formats
Research Articles, Reviews and Mini Reviews, Opinion Papers, Short Communications, letters to the Editor, Case Reports, Editorials

Your Benefits

Your benefits:

Comprehensive approach to drug metabolism research
State-of-the-art research results
Renowned editorial board
High quality peer-review

Drug Metabolism and Personalized Therapy is the official journal of the European Society of Pharmacogenomics and Personalised Therapy (ESPT).

Previous Titles

Founded in 1981 until 2014: Drug Metabolism and Drug Interactions

From 2015 onwards: Drug Metabolism and Personalized Therapy

Other publications in the field

Abstracting and Indexing

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Supplementary Materials

Publication Ethics and Publication Malpractice Statement

Topics

External Links

Volume 36 Issue 2

June 2021

Accessible May 14, 2021

Frontmatter

Page range: i-ii

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Reviews

April 5, 2021

A review on the clinical trials of repurposing therapeutic drugs, mechanisms and preventive measures against SARS-CoV-2

Eleazer U. Ikonne, Victor O. Ikpeazu, Ositadinma C. Ugbogu, Okezie Emmanuel, Ikechukwu P. Nwakuche, Emeka J. Iweala, Eziuche A. Ugbogu

Page range: 73-85

Abstract

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a highly transmittable pathogenic viral infection that causes a disease known as COVID-19. It is a pandemic and public health challenge ravaging the world today. Unfortunately, with the daily increase of infected individuals, there is no known drug approved for the treatment of COVID-19. However, there are therapeutic drugs with the potentials to inhibit endocytic pathways, suppress ribonucleic acid (RNA) polymerase activities, and reduce the replication of SARS-CoV-2. These drugs modifications are aimed at reducing inflammation, time of recovery, and number of deaths. This review is aimed at providing updated information on the clinical manifestations, diagnosis, preventive measures and therapeutic drugs used against SARS-CoV-2. The finding of this review revealed that some of these drugs are transmembrane protease, serine 2, and angiotensin-converting enzyme 2 inhibitors with the capacity to block the entrance/replication of SARS-CoV-2 in a host cell and therefore, may be promising in preventing the spread and mortality of SARS-CoV-2. However, these drugs may cause detrimental health effects such as toxic and non-efficacy issues. Therefore great caution should be employed by health professionals when prescribing these drugs to COVID-19 patients.

Accessible April 5, 2021

Drugs intervention study in COVID-19 management

Muhammad Taher, Noratika Tik, Deny Susanti

Page range: 87-98

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Abstract

By 9 February 2021, the Coronavirus has killed 2,336,650 people worldwide and it has been predicted that this number continues to increase in year 2021. The study aimed to identify therapeutic approaches and drugs that can potentially be used as interventions in Coronavirus 2019 (COVID-19) management. A systematic scoping review was conducted. Articles reporting clinical evidence of therapeutic management of COVID-19 were selected from three different research databases (Google Scholar, PubMed, and Science Direct). From the database search, 31 articles were selected based on the study inclusion and exclusion criteria. This review paper showed that remdesivir and ivermectin significantly reduced viral ribonucleic acid (RNA) activity. On the other hand, convalescent plasma (CP) significantly improved COVID-19 clinical symptoms. Additionally, the use of corticosteroid increased survival rates in COVID-19 patients with acute respiratory distress syndrome (ARDS). Findings also indicated that both hydroxychloroquine and favipiravir were effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, lopinavir–ritonavir combination was not effective against COVID-19. Finally, ribavirin, galidesivir, and sofosbuvir showed potential therapeutic benefit in treating COVID-19, but there is a lack of clinical evidence on their effectiveness against SARS-CoV-2. Remdesivir, ivermectin, favipiravir, hydroxychloroquine, dexamethasone, methylprednisolone, and CP are the therapeutic agents that can potentially be used in COVID-19 management.

Original Articles

Accessible March 29, 2021

CYP2D6 and CYP3A4 variants influence the risk and outcome of COVID-19 infection among rheumatoid arthritis patients maintained on hydroxychloroquine

Mohammad Salem Hareedy, Sonya Mohamed Rashad, Helal F. Hetta, Sara Mahmoud Hassanien, Hebatallah Abdellatif, Manal Hassanien

Page range: 99-111

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Abstract

Objectives Hydroxychloroquine (HCQ) has been used as an off label for the management of coronavirus disease (Covid-19) infection with other drugs. However, different genetic variants can affect the metabolism of HCQ leading to inter-individual differences in its efficacy. In this study, we investigated the effects of variants in CYP2D6, CYP3A4 and CYP3A5 on the risk of Covid-19 infection among patients receiving HCQ for controlling rheumatoid arthritis (RA). Methods A total of 60 patients were genotyped for CYP2D6*2XN, CYP2D6*4, CYP3A4*1B and CYP3A5*2. They were receiving HCQ for the treatment of RA. The patients were evaluated clinically for fever and dry cough, radiologically via chest computed tomography (CT) and immunologically via anti-Covid-19 IgG and IgM titers. Results Variants in CYP2D6 significantly affected the grade of ground glass (CYP2D6*4 AA carriers showed the higher risk for grade 3) and the risk of positive anti-Covid-19 IgM (CYP2D6*2XN CC and CYP3A4*1B AA had the lowest risk), the duration of HCQ, the use of corticosteroids or gender did not affect the Covid-19 status significantly. Conclusions In general, the outcome of the studied patients receiving HCQ was good (no deaths, no intubation needed). CYP2D6 variants could affect the outcome of Covid-19 infection.

March 19, 2021

Metabolizer phenotype prediction in different Peruvian ethnic groups through CYP2C9 polymorphisms

Edward Valencia Ayala, Mylenka Chevarría Arriaga, Eduardo Barbosa Coelho, José Sandoval Sandoval, Alberto Salazar Granara

Page range: 113-121

Abstract

Objectives The CYP2C9 gene have three common alleles, CYP2C9*1 , CYP2C9*2 and CYP2C9*3 , associated with different homozygous ( *1/*1, *2/*2 and *3/*3 ) and heterozygous ( *1/*2 and *1/*3 ) genotypes, which in turn are related to extensive ( g EM), intermediate ( g IM) and poor ( g PM) metabolizers. Likewise, the inter-ethnic variability was intimately associated with different drug metabolism. Therefore, the aim of the present study was predict the metabolizer phenotypes in different Peruvian ethnic groups from lowland (<2,500 m) and highland (>2,500 m). Methods TaqMan genotyping assays were performed in a group of 174 healthy unrelated Peruvian individuals. Results In this study, the allelic comparison between the three eco-regions showed that the CYP2C9*1 was the most common in Andean (96.32%); the *2 was the most frequent in Coast (7.45%, p<0.05). Regarding the *3 was the most common in Amazonian (6.25%, p<0.05). In a corroborative manner, the g EM was the most common in Andean (94.74%), the g IM in Coast (17.02%) and g PM in Amazonian (6.25%) populations. Conclusions Our study provides a valuable source of information about to metabolizer phenotype drugs in different Peruvian ethnic groups. In this way, it could be established suitable genetic-dosage medicaments for various common diseases in these heterogenetic populations.

December 23, 2020

Pharmacogenetic algorithm for predicting daily dose of warfarin in Caucasian patients of Czech origin

Aleš Tomek, Tereza Šrámková, Vojtěch Kaplan, Zuzana Lacinová, Simona Kumstýřová, Martin Šrámek, Anna Olšerová, Petr Janský, Tereza Kolářová, Jiří Neumann, Jaroslava Paulasová Schwabová, Václav Maťoška

Page range: 123-128

Abstract

Objectives Warfarin use is limited by a low therapeutic index and significant interindividual variability of the daily dose. The most important factor predicting daily warfarin dose is individual genotype, polymorphisms of genes CYP2C9 (warfarin metabolism) and VKORC1 (sensitivity for warfarin). Algorithms using clinical and genetic variables could predict the daily dose before the initiation of therapy. The aim of this study was to develop and validate an algorithm for the prediction of warfarin daily dose in Czech patients. Methods Detailed clinical data of patients with known and stable warfarin daily dose were collected. All patients were genotyped for polymorphisms in genes CYP2C9 and VKORC1 . Results Included patients were divided into derivation (n=175) and validation (n=223) cohorts. The final algorithm includes the following variables: Age, height, weight, treatment with amiodarone and presence of variant alleles of genes CYP2C9 and VKORC1 . The adjusted coefficient of determination is 72.4% in the derivation and 62.3% in the validation cohort (p<0.001). Conclusions Our validated algorithm for warfarin daily dose prediction in our Czech cohort had higher precision than other currently published algorithms. Pharmacogenetics of warfarin has the potential in the clinical practice in specialized centers.

Open Access December 24, 2020

Fear of Hypoglycemia in Adults with diabetes mellitus switching to Treatment with IDegAsp Co-formulation to Examine real-world setting: an observational study (The HATICE study)

Ulaş Serkan Topaloğlu, Hatice Kayış Topaloğlu, Melih Kızıltepe, Mesut Kılıç, Sami Bahçebaşı, Sibel Ata, Şeyma Yıldız, Yasin Şimşek

Page range: 129-134

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Abstract

Objectives To evaluate the clinical results of insulin degludec/aspart (IDEgAsp) therapy and its effect on the fear of hypoglycemia. Methods A prospective observational study has been conducted through surveys of 36 patients using insulin because of type 2 diabetes mellitus who initiated treatment with IDegAsp switching from other insulins. Patients, 18–75 years old, were recruited to the study, consecutively. Participants’ age, gender, height, weight, body mass index (BMI), daily insulin dose, glycated hemoglobin (HbA 1c ), hypoglycemia rate, hypoglycemia fear survey (HFS) were recorded at the beginning of the study. By the end of 12th month, data was re-measured and compared with each other. Results HbA 1c was declined by mean of −1.59% (95% CI −1.06 to −2.12, p<0.001). There was also a significant decrease in mean, daily insulin dose, weight and BMI values of patients via IDegAsp. While there was an increase in the amount of dipeptidyl peptidase 4-inhibitors (DPP4-i) and sodium-glucose co-transporter 2-inhibitors (SGLT2-i), there was a decrease in daily injection frequency. There was also a significant decrease in the median values of monthly hypoglycemia rate (from 2.0 to 1.0, p<0.001) and the entire HFS scores (HFS-T: from 1.09 to 0.73, p<0.001; HFS-B: from 0.83 to 0.60, p<0.001; HFS-W: from 1.33 to 0.88, p<0.001). There was a strong positive correlation between ΔHFS-B and daily injection frequency (Rho: 0.398; P: 0.016). Conclusions IDegAsp co-formulation, combined with DPP4-i and/or SGLT2-i, can provide usefulness in terms of rates of hypoglycemia, reduced HbA 1c , less injection administration, and decreased the fear of hypoglycemia in diabetics.

December 30, 2020

Involvement of GABAergic and nitrergic systems in the anxiolytic and hypnotic effects of Curcuma longa: its interaction with anxiolytic-hypnotics

Ismail O. Ishola, Folashade O. Katola, Olufunmilayo O. Adeyemi

Page range: 135-143

Abstract

Objectives Concurrent use of herbs with drugs have become a major healthcare problem. Herb-drug interactions could lead to therapeutic failure or toxicity. Hence, this study seeks to evaluate the impact of combining Curcuma longa rhizome (CL) with selected anxiolytic and hypnotic drugs. Methods CL (100, 200 or 400 mg/kg, p.o.) was administered to mice 1 h before subjecting the animals to elevated plus maze (EPM), hole board test (HBT), open field test (OFT) and rotarod test for anxiolytic-like effect as well as hexobarbitone-induced sleeping time (HIST) for hypnotic activity. The involvement of GABAergic and nitrergic systems in CL-induced anxiolytic and hypnotic actions were also evaluated. The effect of concurrent use of CL with midazolam, imipramine, nifedipine, propranolol and carbamazepine were evaluated in anxiolytic-hypnosis models. Results The peak anxiolytic-like effect of CL was obtained at 400 mg/kg in the EPM and hole-board test without affecting muscle coordination in the rotarod test while the peak hypnosis-potentiation was observed at 100 mg/kg. CL-induced anxiolytic-hypnotic-like effects were reversed by the pretreatment of mice with flumazenil or N G -nitro- l -arginine. Conclusions Curcuma longa possesses anxiolytic and hypnotic effects through its interaction with GABAergic and nitrergic systems. Conversely, co-administration of C. longa with midazolam potentiate barbiturate-induced hypnosis.

December 14, 2020

Quality control, HPTLC analysis, antioxidant and antimicrobial activity of hydroalcoholic extract of roots of qust (Saussurea lappa, C.B Clarke)

Shabnam Ansari, Mohammad Maaz, Iftekhar Ahmad, Syed Kazim Hasan, Sajad Ahmad Bhat, Syed Kazim Naqui, Mohammad Husain

Page range: 145-153

Abstract

Objectives Saussurea lappa , CB Clarke ( S.lappa ) is a perennial herb of the Compositae family. The root of S.lappa has been used for the treatment of various diseases such as hepatitis, jaundice, intestinal worms, bronchial asthma, and a variety of skin diseases. The aim of the study was to ensure quality control of S.lappa and its preparation HAESL (hydroalcoholic extract of S.lappa ) along with assessment of HAESL antimicrobial and antioxidant activities in vitro . Methods HAESL was prepared with 50% ethanol, (v/v). Physiochemical analysis of the root of S.lappa, and phytochemical screening, thin-layer chromatography (TLC), high-performance thin-layer chromatography (HPTLC), and in vitro antimicrobial and antioxidant activity of HAESL were performed using the standard protocol. Results Physiochemical and phytochemical assessments of S.lappa and HAESL showed the greater quality of the drug. HAESL showed the presence of many phytochemical constituents corresponding to colorful spots, peaks, area under the curve, and corresponding Rf values as evident in the TLC and HPTLC analysis. HAESL showed a concentration-dependent effect on radical scavenging activity against DPHH (2,2-diphenyl-1-picrylhydrazyl) and hydroxyl radical with IC50 value of 19.10 μg/mL and 82.23 μg/mL, respectively. HAESL exhibited antimicrobial activity against the growth of micro-organisms such as Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella typhi, Aspergillus flavus , and Candida albicans . HASEL showed no antimicrobial activity against Aspergillus niger . Conclusions The procured and an identified sample of Saussurea lappa was good in quality and the prepared HAESL contained many phytochemical compounds. HAESL substantiated significant antioxidant and antimicrobial activity in vitro.

December 29, 2020

Recombinant human hyaluronidase PH20-mediated dermal spreading activity in mice is not altered by steroids, antihistamines, or salicylic acid

Jessica A. Cowell, Marie A. Printz, Curtis B. Thompson

Page range: 155-163

Abstract

Objectives Drug–drug interaction studies for hyaluronidase safety assessments have evaluated only animal-derived enzyme preparations. We therefore set out to evaluate whether high-dose administration of two antihistamines, a potent corticosteroid, steroid hormone, adrenocorticotropic hormone (ACTH), or salicylic acid would alter the dispersive activity of recombinant human hyaluronidase PH20 (rHuPH20). Methods NCr nu/nu mice were pretreated with diphenhydramine, cetirizine, dexamethasone, estrogen, ACTH, salicylic acid, and/or neutral-buffered saline (NBS). An hour following final pretreatment, dosed mice were anesthetized with ketamine/xylazine and placed in an imaging chamber. A 120 mg/mL immunoglobulin G (IgG) solution with 0.3 μg/mL IgG DL755 (labeled IgG) was injected intradermally, with/without 2,000 U/mL rHuPH20. Fluorescent images of labeled IgG dispersion were acquired ≤20 min post injection. Results Dispersion of high-concentration labeled IgG combined with rHuPH20 was greater at all time points vs. antibody alone. At 20 min post injection (last time point), the antibody dispersion area was significantly increased with rHuPH20 vs. without rHuPH20 (p≤0.005). The relative percent increase in antibody dispersion with rHuPH20 ranged from 22.8‒106.6% over the 20-min time course, compared with the corresponding non-rHuPH20 treated groups. The area of labeled IgG dispersion was statistically similar between rHuPH20 groups pretreated with an active compound and their paired NBS pretreated controls. Conclusions The addition of 2,000 U/mL rHuPH20 to a high-concentration antibody solution reproducibly incre-ased local antibody dispersion. Systemic pretreatment with diphenhydramine, cetirizine, dexamethasone, estrogen, ACTH, or salicylic acid did not affect the enzymatic spreading activity of rHuPH20, as measured by intradermal dispersion of labeled IgG in mice.

Short Communication

December 25, 2020

TCF7L2 rs7903146 C>T gene polymorphism is not associated with hypoglycemia in sulfonylurea-treated type 2 diabetic patients

Georgia Ragia, Evgenia Katsika, Charalampia Ioannou, Vangelis G. Manolopoulos

Page range: 165-168

Abstract

Objectives Hypoglycemia is the most common adverse effect of sulfonylureas (SUs) and a major concern when using these drugs. Transcription factor 7-like 2 (TCF7L2) rs7903146 C>T polymorphism is an established and well characterized genetic marker of type 2 diabetes (T2DM) risk. The aim of the present study was to analyze the potential association of TCF7L2 rs7903146 C>T polymorphism with SU-induced hypoglycemia in a well characterized cohort of SU-treated patients previously genotyped for cytochrome P450 2C9 (CYP2C9) and P450 oxidoreductase (POR). Methods The study group consisted of 176 SU-treated T2DM patients of whom 92 had experienced at least one drug-associated hypoglycemic event. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for TCF7L2 rs7903146 genotyping. Results TCF7L2 rs7903146 C>T genotype and allele frequency did not differ between cases and controls (p=0.745 and 0.671, respectively). In logistic regression analysis adjusted for other factors affecting hypoglycemia, including CYP2C9 and POR genotypes, TCF7L2 rs7903146 C>T polymorphism did not increase the risk of hypoglycemia (OR=1.238, 95% C.I.=0.750–2.044, p=0.405). Conclusions TCF7L2 rs7903146 C>T polymorphism is not associated with SU-induced hypoglycemia. Identifying additional gene polymorphisms associated with SU-induced hypoglycemia is crucial for improving T2DM patient therapy with SUs.

Case Report

Open Access December 30, 2020

Spinal and cerebral hematoma in systemic lupus erythematosus and antiphospholipid syndrome: is drug interaction the culprit?

Emine Duran, Emre Bilgin, Ertuğrul Çağrı Bölek, Oğuzhan Fırat, Elif Bulut, Umut Kalyoncu, Sedat Kiraz, Ömer Karadağ

Page range: 169-172

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Abstract

Objectives Thrombotic events are common in systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). Warfarin is the most commonly used anticoagulant drug for thrombosis treatment, but it is can interact with many drugs, foods, or medicinal herbs. Herein, we presented a case with SLE and APS who was complicated by spinal and cerebral hematoma as a result of warfarin interaction. Case presentation Spinal subdural hematoma and frontal intraparenchymal hematoma were occurred in our patient, who was in remission for 2 years with rituximab, hydroxychloroquine and warfarin. We learned that she had been using some herbal products (shepherd’s purse and horsetail) and phenyramidol for a few days. Spinal and cerebral hematomas caused by the interaction of phenyramidol and warfarin were treated with fresh frozen plasma and vitamin K without the need for surgery. Conclusions The drug interactions with warfarin can cause fatal hemorrhagic or thrombotic events. Especially, the patients with SLE and/or APS using warfarin should be warned not to use different medications or herbal agents.

Ahead of Print / Just Accepted

Ahead of Print / Just Accepted

Volume 36 (2021)

Volume 35 (2020)

Volume 34 (2019)

Volume 33 (2018)

Volume 32 (2017)

Volume 31 (2016)

Volume 30 (2015)

Volume 29 (2014)

Volume 28 (2013)

Volume 27 (2012)

Volume 26 (2011)

Volume 25 (2010)

Issue 1-4

Volume 24 (2009)

Volume 23 (2008)

Volume 22 (2007)

Volume 21 (2006)

Volume 20 (2004)

Volume 19 (2003)

Volume 18 (2001)

Volume 16 (2000)

Volume 17 (2000)

Issue 1-4

Volume 15 (1999)

Volume 14 (1998)

Volume 13 (1997)

Volume 12 (1995)

Volume 11 (1994)

Volume 10 (1992)

Volume 9 (1991)

Volume 8 (1990)

Issue 1-2

Volume 7 (1989)

Volume 6 (1988)

Volume 5 (1987)

Volume 4 (1982)

Volume 3 (1981)

Cite Score	2.5
SCImago Journal Rank	0.346
Source Normalized Impact per Paper	0.600

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Editorial

Editor-in-Chief
Adrián LLerena
CICAB Clinical Research Center, Extremadura University Hospital, Badajoz, Spain
allerena@unex.es

Associate Editor
Vangelis G. Manolopoulos, Dept. of Pharmacology, Democritus University of Thrace Medical School, Alexandroupolis, Greece

Editorial Board
Mongi Benjeddou, Dept. of Biotechnology, University of the Western Cape, Cape Town, South Africa
Bing Chen, Shanghai, Dept. of Laboratory Medicine, Jiaotong University, Shanghai, P.R. China
Jaroslav Hubacek, Centre for Experimental Medicine, Institute for Clinical and Experimental Medicine
Magnus Ingelman-Sundberg, Dept. of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
Giorgio D. Kotzalidis, Dept. of Neurosciences, Mental Health, and Sensory Organs, Sapienza University, Rome, Italy
Janja Marc, Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia
Urs A. Meyer, Dept. of Pharmacology, Biocenter of the University of Basel, Basel, Switzerland
Sujit Nair, Pharmaceutical Sciences, University of Mumbai, Mumbai, India
Charity Nofziger, Insitute of Pharmacology and Toxicology, Paracelsus Medical University, Salzburg, Austria
Ana Peiró, University General Hospital of Alicante, Alicante, Spain
Georgia Ragia, Laboratory of Pharmacology, Democritus University of Thrace, Alexandroupolis, Greece
Jae-Gook Shin, Pharmacogenomics Research Center, Inje University College of Medicine, Busan, South Korea
Maurizio Simmaco, Dept. of Neurosciences, Faculty of Medicine & Psychology, Sapienza University of Rome, Rome, Italy
Sanja Stankovic, Faculty of Biology, University of Belgrade, Belgrade, Serbia
Enrique Terán, School of Medicine, Universidad San Francisco de Quito, Quito, Ecuador
Ron H.N. van Schaik, Dept. of Clinical Chemistry, Erasmus Medical Center, Rotterdam, The Netherlands
Sophie Visvikis-Siest, INSERM U525, University of Lorraine, Nancy, France

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Heike Jahnke, Journal Editor
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(Deutsch)

Online ISSN: 2363-8915
Type: Journal
Language: English
Publisher: De Gruyter
First published: December 1, 1980
Publication Frequency: 4 Issues per Year
Audience: researchers and professionals in the field of pharmacology, basic scientists, translational researchers, industry scientists and professionals in the field of pharmacology