Drug Metabolism and Personalized Therapy

Official journal of the European Society of Pharmacogenomics and Personalised Therapy

ISSN: 2363-8915

First published: December 1, 1980

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

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Volume 36 Issue 1

March 2021

Frontmatter

March 22, 2021 Page range: i-ii

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Review

Herbal approach for the management of C0VID-19: an overview

Sana Fatima, Nafis Haider, Md Anzar Alam, Mohd Abdul Gani, Rafeeque Ahmad, Murtada Taha November 2, 2020 Page range: 1-8

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Abstract

COVID-19 is the most recently discovered coronavirus infectious disease and leads to pandemic all over the world. The clinical continuum of COVID-19 varies from mild illness with non-specific signs and symptoms of acute respiratory disease to extreme respiratory pneumonia and septic shock. It can transmit from animal to human in the form of touch, through the air, water, utensils, fomite and feco-oral route blood. The pathogenesis and clinical features of COVID-19 be the same as the clinical manifestation associated epidemic Fever. In Unani medicine, various herbal drugs are described under the caption of epidemic disease. Great Unani scholar also Avicenna (980–1037 AD) recommended that during epidemic condition movement should be restricted, self-isolation, fumigation around the habitant with perfumed herbs (Ood, Kafoor, Sumbuluttib, Saad Kofi, Loban, etc.), and use of appropriate antidotes (Tiryaqe Wabai) and vinegar (Sirka) as prophylaxis. Herbal approach is based on single (Unnab— Ziziphus jujuba , Sapistan— Cordia myxa , Bahidana— Cydonia oblonga , Khatmi—Althea officinalis, Khubazi— Malva sylvestris , Zafran— Crocus sativus , Sibr— Aloe barbedensis , Murmuki— Commiphora myrrha , Darchini— Cinnamomum zeylanicum , Qaranfal— Syzygium aromaticum , Rihan— Oscimum sanctum , Habtus Sauda— Nigella sativa , Aslus Sus— Glycyrrhiza glabra , Maghze Amaltas— Cassia fistula and Adusa— Adhatoda vasica ) and compound drugs (Habbe Bukhar, Sharbat Khaksi, Sharbat Zanjabeel, Naqu Nazla, Majoon Chobchini, Jawrish Jalinus and Khamira Marvareed) most of them are claimed for anti-viral, anti-pyretic, blood purifier, cardioprotective and expectorant activities. Traditionally most of the herbal practitioners are using it.

Original Articles

Clinically important drug–drug interactions in patients admitted to hospital with COVID-19: drug pairs, risk factors, and management

Amir Ali Mahboobipour, Shadi Baniasadi December 23, 2020 Page range: 9-16

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Abstract

Objectives Coronavirus disease 2019 (COVID-19) is an emerging viral infection without any approved treatment. Investigational therapies for COVID-19 may cause clinically important drug–drug interactions (DDIs). We aimed to study potential DDIs (pDDIs) and their risk factors in COVID-19 patients admitted to the hospital. Methods We conducted a cross-sectional study in a tertiary respiratory hospital dedicated to COVID-19 patients. The Lexi-Interact database was used to investigate clinically important pDDIs. The database output including interacting drug pairs, risk rating, reliability rating, mechanism, and management was evaluated. Associations between the occurrence of pDDIs and probable risk factors were assessed by logistic regression analysis. Results Medical charts of 227 patients were reviewed. About 38% of the patients had at least one clinically important pDDI. More than half of the interactions were between protease inhibitors (lopinavir/ritonavir) and regularly prescribed medications for the management of comorbidities or COVID-19 symptoms (e.g., atorvastatin, alprazolam, salmeterol, and tamsulosin). Ischemic heart disease, chronic respiratory diseases, and ICU admission were significantly associated with the occurrence of pDDIs. Conclusions We recommend considering the risk factors for the emergence of clinically important DDIs in the pharmacotherapy of COVID-19 patients. Using an alternative medication or dose adjustments may be required in high-risk patients.

Spinal and general anesthesia produces differential effects on oxidative stress and inflammatory cytokines in orthopedic patients

Peter A. Aremu, Abayomi M. Ajayi, Benneth Ben-Azu, Olayinka T. Orewole, Solomon Umukoro October 7, 2020 Page range: 17-23

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Abstract

Objectives The contribution of anesthetic procedure to surgical stress and postoperative complications has been attributed to increased oxidative stress and release of inflammatory cytokines. Thus, the levels of oxidative stress biomarkers and inflammatory cytokines in patients with general anesthesia (GA) and spinal anesthesia (SA) that underwent open reduction and internal fixation (ORIF) in orthopedic surgery at Federal Teaching Hospital, Ido-Ekiti, Ekiti state, Nigeria were investigated. Methods Forty patients were randomly distributed into two groups (n = 20) namely GA and SA. Blood samples were collected before and after surgery for estimation of glucose, oxidative stress biomarkers (malondialdehyde [MDA], glutathione, catalase and nitrile) and inflammatory cytokines (tumor necrosis factor-α [TNF-α] and interleukin-6) levels. Results The post-operative blood glucose level was higher than the pre-operative value (p<0.5) in the two groups. There were significant (p<0.05) changes in MDA concentration and catalase activity in patients with GA in the post-operative stage relative to preoperative phase. There were no significant differences in glutathione, nitrite and interleukin-6 contents between the two groups. The patients with SA had higher levels of TNF-α in the post-operative stage. Conclusions These findings suggest that anesthesia has differential effects on oxidative stress and inflammatory cytokines in patients with ORIF orthopedic surgery.

Immunogenicity of antitumor necrosis factor therapy in patients with spondyloarthritis

Ines Mahmoud, Leila Rouached, Aicha Ben Tekaya, Olfa Saidane, Selma Bouden, Saoussen Jradi, Imen Sfar, Rawdha Tekaya, Kawther Ben Abdelghani, Yousr Lakhoua Gorgi, Leila Abdelmoula November 6, 2020 Page range: 25-32

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Abstract

Objectives To evaluate the serum dosage of the biomedicine (DBM) and the incidence of antidrug antibody (ADA) against antitumor necrosis factor (TNF) in spondyloarthritis, and to demonstrate the influence of these parameters on the clinical efficiency. Methods We conducted a cross-sectional multicentric study including patients with spondylarthritis (SpA) under antiTNF (infliximab [INF], etanercept [ETA] and adalimumab [ADL]) for at least 6 months. A dosage of the ADA and DBM were practiced by the immuno-enzymatic essay. Result Seventy one patients were recruited. Disease modifying antirheumatic drugs (DMARDs) were associated with anti-TNF in 30%. ADA was positive in 54% for INF, 33% for ADL and 0% for ETA with a significant difference(p<0.0001). Immunogenicity was correlated to a bad therapeutic response (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]≥4)(p=0.04). The DBM was inversely correlated with the rate of ADA for patients treated with INF(p<0.0001) and ADL(p<0.0001). The DBM was also inversely correlated with BASDAI of INF(p=0.03) and ADL (p=0.01). ADA was significantly associated with an anterior switch of anti TNF(p=0.04), the use of INF(p=0.002), presence of coxitis(p=0.01) and higher body mass index (BMI)(p=0.007). DMARDs associated with anti TNF were not a protective factor for positive ADA. In a multivariate study, only INF and BMI were independent factors of positive ADA. Conclusion The ADA formation lowered the DBM and favored the therapeutic failure.

Biochip-based approach for comprehensive pharmacogenetic testing

Anna Yu. Ikonnikova, Marina A. Filippova, Sergey A. Surzhikov, Victoria O. Pozhitnova, Ruslan E. Kazakov, Tatiana S. Lisitsa, Sergey A. Belkov, Tatiana V. Nasedkina December 15, 2020 Page range: 33-40

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Abstract

Objectives Individual sensitivity to many widely used drugs is significantly associated with genetic factors. The purpose of our work was to develop an instrument for simultaneous determination of the most clinically relevant pharmacogenetic markers to allow personalized treatment, mainly in patients with cardiovascular diseases. Methods Multiplex one-step polymerase chain reaction (PCR) followed by hybridization on a low-density biochip was applied to interrogate 15 polymorphisms in the following eight genes: VKORC1 –1639 G>A , CYP4F2 1297 G>A , GGCX 2374 C>G , CYP2C9 *2,*3 (430 C>T, 1075 A>C) , CYP2D6 *3,*4, *6, *9, *41 (2549delA, 1846 G>A, 1707delT, 2615_2617delAAG, 2988 G>A), CYP2C19 *2,*3,*17 (681 G>A, 636 G>A, −806 C>T) , ABCB1 (3435 C>T) , SLCO1B1 *5 . Results Two hundred nineteen patients with cardiovascular diseases (CVD) and 48 female patients with estrogen receptor (ER)-positive breast cancer (BC) were genotyped. Of the 219 CVD patients, 203 (92.7%) carried one or more actionable at-risk genotypes based on VKORC1/CYP2C9, CYP2C9, CYP2C19, SLCO1B1, and CYP2D6 genotypes. Among them, 67 patients (30.6%) carried one, 58 patients (26.5%) carried two, 51 patients (23.3%) carried three, 26 patients (11.9%) carried four, and one patient (0.4%) carried five risk actionable genotypes. In the ER-positive BC group 12 patients (25%) were CYP2D6 intermediate or poor metabolizers. Conclusions The developed biochip is applicable for rapid and robust genotyping of patients who were taking a wide spectrum of medications to optimize drugs and dosage and avoid adverse drug reactions in cardiology, oncology, psychiatry, rheumatology and gastroenterology.

Clinical efficacy of Majoon Falasfa and Roghan-e-Surkh in post-stroke-disability: an open labeled, pre-post analysis

Izhar Ahmad, Tanzeel Ahmad, Mohd Aleemuddin Quamri October 5, 2020 Page range: 41-46

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Abstract

Objectives Stroke is one of the leading causes of death and disability in India. The estimated adjusted prevalence rate of stroke range, 84–262/100,000 in rural and 334–424/100,000 in urban areas. A deficit in motor function affects mobility, daily activity of life. Rehabilitation is the most useful method to reduce deficit motor function. Hemiplegia ( Falij ) , is one of the most common disability resulting from stroke has been described by Unani physicians, and they treat the disease effectively on the principle of Tanqia (evacuation) and Tadeel (alterative). Hence, a study contemplated to determine the effectiveness of Majoon Falasfa (MF) and Roghan-e-Surkh (RS) in post-stroke disability. Methods This trail was an open labeled, pre-post analysis, carried out at the National Institute of Unani Medicine (NIUM), on thirty (n=30) subjects of both genders, with post-stroke disability, and given MF 6 g orally with water in the morning and evening on empty stomach daily along with massage of 15 mL RS on the affected part once a day for 45 days with three follow up fortnightly (i.e. 15th, 30th, and 45th day). Patients were assessed on each follow up based on Barthel Index of Activities of Daily Living (ADL). Pre- and post-treatment values of the scale were analyzed statistically using Student’s ‘t’ test and paired Proportion test. Results The treatment difference as pre-post values determine with Barthel Index was found statistically highly significant (p<0.001). Safety parameters found within the normal range. Conclusions Finding of this trial recommended that both Unani formulations are effective in the management of post-stroke disability, and it can be used to decrease the dependency and boost the quality of life of the patients. No adverse effect was noted during the treatment of test formulations.

Ascorbic acid improves extrapyramidal syndromes and corpus striatal degeneration induced by dopamine-2 receptor inhibition in Wistar rats

Sirajo U. Mujittapha, Murtala Kauthar, Ishola O. Azeez, John C. Oyem November 2, 2020 Page range: 47-52

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Abstract

Objectives The prolonged uses of fourth-generation antipsychotics have been implicated in inducing extrapyramidal syndromes characterized by the motor deficit. This was attributed to the loss of dopamine-2 receptor (D2R) signaling. However, ascorbic acid (SVCT2R stimulation) in the brain is proposed to modulate D2R activity. We, therefore, investigated the beneficial roles of ascorbic acid in improving the extrapyramidal symptoms seen in D2R loss. Methods Twenty adult male Wistar rats of average weight 200 g were distributed randomly into four groups. The control (NS) received normal saline for 28 days, Untreated D2R inhibition group (−D2R) received normal saline for seven days and then subsequently received chlorpromazine for 21 days, D2R inhibition group treated with ascorbic acid (−D2R+SVCT2R) received chlorpromazine for 21 days and was subsequently treated with ascorbate for seven days while the withdrawal group (WG) received chlorpromazine for 21 days and subsequently received normal saline for seven days. Motor deficits were assessed using a rotarod and cylinder test. The corpus striatum was harvested, processed, and stained using H&E and Nissl stains. Cellular density was analyzed using Image J software 1.8.0. Results Motor deficit was observed in −D2R animals administered chlorpromazine with less improvement in WG compared to control (p<0.05) in both rotarod and cylinder test. Ascorbic acid (SVCT2R stimulation) significantly (p<0.001) improved the latency of fall and climbing attempts observed in −D2R animals. The density of basophilic trigoid bodies was significantly (p<0.001) restored in −D2R+SVCT2R group, suggesting recovery of neural activity in the corpus striatum. Moreover, the hallmarks of neuronal degeneration were less expressed in the ascorbic acid treatment groups. Conclusions Ascorbic acid putatively ameliorates extrapyramidal symptoms observed in D2R blockage by chlorpromazine in Wistar rats.

Rutin ameliorates scopolamine-induced learning and memory impairments through enhancement of antioxidant defense system and cholinergic signaling

Ismail O. Ishola, Taiwo G. Olubodun-Obadun, Mariam A. Ojulari, Olufunmilayo O. Adeyemi September 30, 2020 Page range: 53-61

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Abstract

Objectives The brain’s cholinergic system occupies a central role in normal cognition and age-related cognitive decline, including Alzheimer’s disease (AD). This study sought to investigate the role of antioxidant defense and cholinergic systems on rutin-induced antiamnesia in mice. Methods Rutin (1, 5, or 50 mg/kg, p.o.) or vehicle (10 ml/kg, p.o.) was administered for three consecutive days. One hour post-treatment on day 3, scopolamine (3 mg/kg, i.p) was given, 5 min post-scopolamine injection, open field, Y-maze, or Morris water maze (MWM) (five days consecutive training sessions) tasks was carried out. The mice were sacrificed on day 7 to assays for biomarkers of oxidative stress and cholinergic system. Results Scopolamine significantly reduced spontaneous alternation behavior in Y-maze and prolonged escape latency in MWM tasks when compared to vehicle-treated control indicative of working memory and spatial learning deficits. However, the pretreatment of mice with rutin (1, 5, or 50 mg/kg) prevented scopolamine-induced working memory and spatial learning impairments without affecting spontaneous locomotor activity. Scopolamine-induced nitrosative/oxidative stress and increased acetylcholinesterase activity in the prefrontal cortex and hippocampus were significantly attenuated by the pretreatment of mice with rutin. Conclusions rutin restored cognitive function in scopolamine-induced amnesia through enhancement of antioxidant defense and cholinergic systems.

Adansonia digitata L. leaf extract attenuates lead-induced cortical histoarchitectural changes and oxidative stress in the prefrontal cortex of adult male Wistar rats

Vivian Atuadu, Ben-Azu Benneth, John Oyem, Emmanuel Esom, Chris Mba, Kate Nebo, Godswill Ezemeka, Chike Anibeze October 22, 2020 Page range: 63-71

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Abstract

Objectives Adansonia digitata L. is popularly known for the management of various neurological diseases in ethno-medicine. Studies have shown that lead toxicity is a possible risk factor for early onset of neurodegenerative disease. Hence, this study was designed to evaluate the effect of A. digitata aqueous leaf extract (ADALE) against lead-induced oxidative stress and histo-architectural changes in the prefrontal cortex of adult Wistar rats. Methods Saline (10 mL/kg), ADALE (500 and 1000 mg/kg) and EDTA (55 mg/kg) were pretreated orally 30 min prior to lead acetate (LA) (120 mg/kg) administration to male Wistar rats (n=7) for 21 days. Thereafter, standard biochemical (superoxide dismutate, catalase, glutathionxe and malondialdehyde), histological (H&E) and histochemical assessment (crystyl fast violet stain for nissil substance) were carried out in the prefrontal cortex. Results ADALE significantly (p<0.05) reversed LA-induced oxidative stress, as evidenced by increased catalase, superoxide dismutase and oxidized glutathione levels, and decreased malondialdehyde concentration in the prefrontal cortex. Also, the increase chromatolysis and neuronal pyknosis of the pyramidal neurons of the prefrontal cortex were significantly attenuated by ADALE. Conclusions The result of this study showed that A. digitata aqueous leaf extract attenuated lead acetate-induced cortical neurodegeneration via inhibition of oxidative stress.

Ahead of Print / Just Accepted

Ahead of Print / Just Accepted

Volume 36 (2021)

Issue 1

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	2.4
SCImago Journal Rank	0.282
Source Normalized Impact per Paper	0.476

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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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(Deutsch)

Drug Metabolism and Personalized Therapy

Official journal of the European Society of Pharmacogenomics and Personalised Therapy

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