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  • 1. Babaoglu, Melih O
    et al.
    Yasar, Umit
    Sandberg, Mia
    Eliasson, Erik
    Dahl, Marja-Liisa
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Klinisk farmakologi.
    Kayaalp, S Oguz
    Bozkurt, Atila
    CYP2C9 genetic variants and losartan oxidation in a Turkish population.2004In: Eur J Clin Pharmacol, ISSN 0031-6970, Vol. 60, no 5, p. 337-42Article in journal (Refereed)
  • 2. Bertilsson, Leif
    et al.
    Dahl, Marja-Liisa
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Klinisk farmakologi.
    Dalén, Per
    AL-Shurbaji, Ayman
    Molecular genetics of CYP2D6: Clinical relevance with focus on psychotropic drugs2002In: Br J Clin Pharmacol, Vol. 53, p. 111-122Article in journal (Refereed)
  • 3. Carlsson, B
    et al.
    Olsson, G
    Reis, M
    Wålinder, J
    Nordin, C
    Lundmark, J
    Scordo, Gabriella
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Dahl, Marja-Liisa
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Bengtsson, F
    Ahlner, J
    Enantioselective analysis of citalopram and metabolites in adolecents.2001In: Ther Drug Monit, Vol. 23, p. 658-Article in journal (Refereed)
  • 4. Ceder, Gunnel
    et al.
    Dahl, Marja-Liisa
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Klinisk farmakologi.
    Trafik och läkemedel2007In: FASS 2007, 2007, p. 2164-2166Chapter in book (Other scientific)
  • 5. Ceder, Gunnel
    et al.
    Dahl, Marja-Liisa
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Klinisk farmakologi.
    Trafik och läkemedel2008In: FASS 2008, 2008, p. 2380-2382Chapter in book (Other scientific)
  • 6. Ceder, Gunnel
    et al.
    Dahl, Marja-Liisa
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Klinisk farmakologi.
    Dehlin, Ove
    Ysander, Lars
    Trafik och läkemedel2005In: FASS, 2005, p. 2204-2206Chapter in book (Other scientific)
  • 7. Ceder, Gunnel
    et al.
    Dahl, Marja-Liisa
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Klinisk farmakologi.
    Dehlin, Ove
    Ysander, Lars
    Trafik och läkemedel2003In: FASS 2003, 2003, p. 1837-1839Chapter in book (Other scientific)
  • 8. Ceder, Gunnel
    et al.
    Dahl, Marja-Liisa
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Klinisk farmakologi.
    Dehlin, Ove
    Ysander, Lars
    Trafik och läkemedel2004In: FASS 2004, 2004, p. 1927-1929Chapter in book (Other scientific)
  • 9. Ceder, Gunnel
    et al.
    Dahl, Marja-Liisa
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Klinisk farmakologi.
    Dehlin, Ove
    Ysander, Lars
    Trafik och läkemedel2006In: FASS 2006, 2006, p. 2827-2829Chapter in book (Other scientific)
  • 10.
    Dahl, Marja-Liisa
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Klinisk farmakologi.
    Cytochrome p450 phenotyping/genotyping in patients receiving antipsychotics: useful aid to prescribing?2002In: Clin Pharmacokinet, ISSN 0312-5963, Vol. 41, no 7, p. 453-70Article in journal (Refereed)
  • 11.
    Dahl, Marja-Liisa
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Farmakogenetik för individualiserad läkemedelsbehandling.2003In: Laboratoriet, Vol. 2, p. 6-8Article in journal (Other scientific)
  • 12.
    Dahl, Marja-Liisa
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Scordo, Maria Gabriella
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Cytochromes P4502006In: Psychopharmacogenetics, M Springer science + Businesss Media Inc , 2006Chapter in book (Refereed)
  • 13. Gokalp, Osman
    et al.
    Gunes, Arzu
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Cam, Hakan
    Cure, Erkan
    Aydin, Osman
    Tamer, Mehmet Numan
    Scordo, Maria Gabriella
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Dahl, Marja-Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Mild hypoglycaemic attacks induced by sulphonylureas related to CYP2C9, CYP2C19 and CYP2C8 polymorphisms in routine clinical setting2011In: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 67, no 12, p. 1223-1229Article in journal (Refereed)
    Abstract [en]

    To evaluate the impact of polymorphisms in the cytochrome P450 (CYP) 2C9, 2C19 and 2C8 genes on the risk of mild hypoglycaemic attacks in patients treated with sulphonylureas. One hundred and eight type 2 diabetic patients (50 men, 58 women), treated with oral antidiabetics, including at least one from the sulphonylurea group (glimepiride n = 50, gliclazide n = 46, or glipizide n = 12) for 3 months or longer, were included in the study. Symptoms of hypoglycaemia (sweating, tremor, anxiety and palpitations) during a 3 month period were recorded and confirmed by home glucose measurements. Gender, age, body mass index, creatinine clearance, HbA1c, oral antidiabetic dose and concomitant medication were assessed together with functional CYP2C9, CYP2C19 and CYP2C8 polymorphisms, analysed by real-time PCR methods. Fifteen patients (eight men, seven women) reported hypoglycaemia symptoms which were validated by their home glucose measurements (< 70 mg/dl). Heterozygosity and homozygosity for CYP2C9 variant alleles (*2 or *3) tended to be more frequent among patients who reported hypoglycaemic attacks (60 and 7%) than those who did not (39 and 3%). Similarly, the CYP2C8*1/*3 genotype tended to be more frequent in patients with (47%) than without (27%) hypoglycaemia, while no such trend was observed for CYP2C19 variants. However, only in the gliclazide group a significant association between CYP2C9 genotype and hypoglycaemic attacks was observed (P = 0.035). None of the other covariates showed any significant association with the risk of hypoglycaemic attacks. CYP2C9 polymorphisms leading to decreased enzyme activity show a modest impact on the risk of mild hypoglycaemia attacks during oral antidiabetic treatment, with a significant association in patients treated with gliclazide.

  • 14.
    Gunes, Arzu
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Scordo, Maria Gabriella
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Jaanson, Peeter
    Dahl, Marja-Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Serotonin and dopamine receptor gene polymorphisms and the risk of extrapyramidal side effects in perphenazine-treated schizophrenic patients2007In: Psychopharmacology, ISSN 0033-3158, E-ISSN 1432-2072, Vol. 190, no 4, p. 479-484Article in journal (Refereed)
    Abstract [en]

    Rationale: Perphenazine, a classical antipsychotic drug, has the potential to induce extrapyramidal side effects (EPS). Dopaminergic and serotonergic pathways are involved in the therapeutic and adverse effects of the drug. Objectives: To evaluate the impact of polymorphisms in the dopamine D 2 and D3 and serotonin 2A and 2C receptor genes (DRD2, DRD3, HTR2A, and HTR2C) on short-term effects of perphenazine monotherapy in schizophrenic patients. Materials and methods: Forty-seven Estonian inpatients were evaluated before and after 4-6 weeks of treatment by Simpson-Angus rating scale, Barnes scale, and Positive and Negative Symptom Scale. Genotyping was performed for common DRD2, DRD3, HTR2A, and HTR2C gene polymorphisms, previously reported to influence receptor expression and/or function. Results: Most of the patients (n = 37) responded to the treatment and no significant association was observed between the polymorphisms and antipsychotic response. The 102C allele of HTR2A and the -697C and 23Ser alleles of HTR2C were more frequent among patients with EPS (n = 25) compared to patients without EPS (n = 22) (p = 0.02, 0.01, and 0.02, respectively). The difference between patients with and without EPS in variant allele frequencies remained significant after multiple model analyses including age, gender, and duration of antipsychotic treatment as covariants. There was no significant association between EPS occurrence and polymorphisms in the DRD2 and DRD3 genes. Conclusions: An association was observed between polymorphisms in HTR2A and HTR2C genes and occurrence of acute EPS in schizophrenic patients treated with perphenazine monotherapy. Larger study populations are needed to confirm our findings.

  • 15.
    Hedenmalm, Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Güzey, Cüneyt
    Dahl, Marja-Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Yue, Qun-Ying
    Spigset, Olav
    Risk factors for extrapyramidal symptoms during treatment with selective serotonin reuptake inhibitors, including cytochrome P-450 enzyme, and serotonin and dopamine transporter and receptor polymorphisms2006In: Journal of Clinical Psychopharmacology, ISSN 0271-0749, E-ISSN 1533-712X, Vol. 26, no 2, p. 192-7Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Extrapyramidal symptoms (EPS) are rare adverse drug reactions to selective serotonin reuptake inhibitors (SSRIs). This study aimed to investigate the potential risk factors for EPS associated with SSRIs including polymorphisms of cytochrome P-450 isoenzymes, and serotonin and dopamine transporters and receptors. METHODS: All spontaneous adverse drug reaction reports received by the Swedish Medical Products Agency until December 1999 that were coded with EPS and judged to be at least possibly related to SSRI treatment were included in the study. Reporting physicians received a form for collection of relevant information including current and previous use of SSRIs and antipsychotics, alcohol or substance abuse, central nervous system damage, a history of epilepsy or EPS, and a family history of Parkinson disease. A blood sample was also requested for genotyping of selected cytochrome P-450, and serotonin and dopamine transporter and receptor mutations. RESULTS: A total of 64 cases of EPS were reported. Twenty-eight forms (46%) were returned, and 20 blood samples were obtained. Identified potential risk factors included age of 65 years or older and the presence of the A1 allele of the D2 dopamine receptor gene (DRD2) Taq1A polymorphism (relative risk, 2.4; 95% confidence interval, 1.2-4.5 vs literature controls). No relationship was apparent for sex, drug dose, or other genetic polymorphisms. At least 1 additional potential risk factor for EPS, such as a history of central nervous system damage, alcohol or substance abuse, epilepsy, Parkinson disease, previous or current exposure to antipsychotic drugs, concomitant treatment with other antidopaminergic or serotonergic agents, or a history of EPS, was found in 93% of the cases. CONCLUSION: The risk of EPS with SSRIs seems to increase with advanced age and with the presence of the A1 allele of DRD2 Taq1A polymorphism. Because of the small sample size of our study and the use of historical controls rather than patients who did not experience EPS during SSRIs treatment, the DRD2 finding is preliminary and needs to be replicated in other studies before firm conclusions can be drawn. At least 1 additional potential risk factor was found in almost all cases.

  • 16. Holmgren, P
    et al.
    Carlsson, B
    Zackrisson, A-L
    Lindblom, B
    Dahl, Marja-Liisa
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Scordo, Maria Gabriella
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Druid, H
    Ahlner, J
    Enantioselective analysis of citalopram and its metabolites in postmortem blood and genotyping for CYP2D6 and CYP2C19.2004In: J Anal Toxicol., Vol. 28, p. 94-Article in journal (Refereed)
  • 17. Hulter Åsberg, Kerstin
    et al.
    Dahl, Marja-Liisa
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Klinisk farmakologi.
    Widerlöv, Erik
    Antipsykotiska läkemedel till äldre patienter: Terapirekommendationer2004Other (Other scientific)
  • 18. Josefsson, Ann
    et al.
    Sydsjö, Gunilla
    Berg, Göran
    Dahl, Marja-Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Wadelius, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Nordin, Conny
    CYP2D6 genotypes and depressive symptoms during late pregnancy and postpartum2004In: Nordic Journal of Psychiatry, ISSN 0803-9488, E-ISSN 1502-4725, Vol. 58, no 1, p. 61-4Article in journal (Refereed)
    Abstract [en]

    The aim of this exploratory was to investigate the theory of a relation between cytochrome P450 2D6 (CYP2D6) genotype and depressive symptoms in late pregnancy and/or postpartum. We studied 145 women with depressive symptoms. CYP2D6 genotype was analysed in leukocyte DNA by polymerase chain reaction (PCR). There were no significant differences in CYP2D6 genotypes between the groups of women being depressed during and/or after pregnancy. The frequencies of CYP2D6 genotypes did not differ from other European studies. This study cannot confirm that depressive symptoms in late pregnancy and postpartum are connected with CYP2D6 genotype. It is, however, noteworthy that the frequency of ultrarapid metabolizers was higher than in a general Caucasian population. This warrants further exploration in a greater study sample, but should also be investigated in a general population with major depression.

  • 19. Lindh, Jonatan D
    et al.
    Holm, Lennart
    Dahl, Marja-Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Alfredsson, Lars
    Rane, Anders
    Incidence and predictors of severe bleeding during warfarin treatment2008In: Journal of Thrombosis and Thrombolysis, ISSN 0929-5305, E-ISSN 1573-742X, Vol. 25, no 2, p. 151-159Article in journal (Refereed)
    Abstract [en]

    Background Optimal warfarin prescription requires correct, individualized assessment of the warfarin-related bleeding risk, which randomised controlled trials may underestimate . Observational studies have reported a range of bleeding risks that differ 40-fold. This variation may be caused by time trends, variation in bleeding definition and study subject selection. We investigated the incidence of, and risk factors for severe bleeding in un-selected warfarin-treated patients from Sweden. Methods Between 2001 and 2005, 40 centres recruited warfarin-naive patients commencing warfarin therapy and followed them prospectively with continuous registration of clinical data. The primary outcome was severe bleeding, according to the WHO universal definition of severe adverse drug reactions. The influence of potential risk factors was investigated by means of a Cox proportional-hazards model. Result A total of 1523 patients contributed 1276 warfarin-exposed patient-years. The incidence of first-time severe bleeding was 2.3 per 100 patient-years (95% confidence interval 1.4 to 3.1). Male sex and use of drugs potentially interacting with warfarin were the only independent risk factors of severe bleeding, with hazard ratios of 2.8 and 2.3, respectively. Age, target International Normalized Ratio (INR), time spent outside target INR range, and warfarin dose requirement were not significantly associated with bleeding risk. Conclusions The risk of severe bleeding in a large naturalistic, prospective cohort of first-time warfarin users was lower than reported in some previous reports. Male gender was an independent predictor of severe bleeding as was the receipt of warfarin-interacting medications at the onset of anticoagulation therapy. Further studies are required to evaluate the effect these findings may have on the quality of current risk-benefit analysis involved in warfarin prescription.

  • 20. Melkersson, Kristina
    et al.
    Dahl, Marja-Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Adverse metabolic effects associated with atypical antipsychotics: literature review and clinical implications2004In: Drugs, ISSN 0012-6667, E-ISSN 1179-1950, Vol. 64, no 7, p. 701-23Article in journal (Refereed)
    Abstract [en]

    Adverse metabolic effects, such as diabetes mellitus, lipid abnormalities and weight gain, have increasingly been recognised with the use of the newer, so-called atypical antipsychotic drugs. This article reviews the current literature in the field and attempts to answer the question of whether the atypical antipsychotics differ in their effects on glucose-insulin homeostasis and lipid metabolism. It also addresses how then to manage the use of the atypical antipsychotics that do interfere with these metabolic systems. Differences in effects of atypical antipsychotics on leptin levels are also summarised and put into context; bodyweight gain associated with atypical antipsychotics is reviewed elsewhere.In summary, there are no large controlled trials published quantifying the prevalence of adverse effects on glucose-insulin homeostasis and lipid metabolism in patients receiving atypical antipsychotics. Nevertheless, the published articles and case reports reviewed in this article give a fairly good view of those adverse effects occurring with clozapine, olanzapine and risperidone, whereas little data are available regarding quetiapine, ziprasidone and zotepine, and no data exist for amisulpride and aripiprazole. Estimated rankings of the atypical agents, based on the available literature, show that the relative risk of glucose intolerance/diabetes mellitus, hyperlipidaemia and hyperleptinaemia is highest for clozapine and olanzapine, moderately high for quetiapine, rather low for risperidone and lowest for ziprasidone. Since adverse metabolic effects of atypical antipsychotics may have a negative influence on both the antipsychotic treatment outcome as well as the physical health of the patient, these effects have to be recognised and adequately managed. In this review, recommendations for prevention and treatment of the adverse metabolic effects are outlined.

  • 21. Melkersson, Kristina
    et al.
    Dahl, Marja-Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hulting, Anna-Lena
    Guidelines for prevention and treatment of adverse effects of antipsychotic drugs on glucose-insulin homeostasis and lipid metabolism2004In: Psychopharmacology, ISSN 0033-3158, E-ISSN 1432-2072, Vol. 175, no 1, p. 1-6Article in journal (Refereed)
    Abstract [en]

    RATIONALE: With the antipsychotic drugs available today, especially with some of the newer, atypical antipsychotics, metabolic side effects, such as weight gain, diabetes mellitus and lipid abnormalities, have become a complication to the drug therapy that have to be recognized and treated. OBJECTIVE: The aim of this article is to suggest guidelines for prevention and treatment of adverse effects of antipsychotics on glucose-insulin homeostasis and lipid metabolism, whereas strategies for management of antipsychotic-induced weight gain are summarized elsewhere. METHOD: The guidelines are based on results of experimental and clinical studies presented in the article, as well as on a recently published review of 180 articles in the field. RESULTS: Both conventional and atypical antipsychotics can indirectly, by causing obesity, promote development of insulin resistance and type-2 diabetes. In addition, some atypical agents probably directly induce hyperinsulinemia, followed by weight gain, insulin resistance and drug-induced, sometimes insulin-dependent, diabetes. CONCLUSION: In this article, guidelines for the management of adverse metabolic effects of antipsychotics are described.

  • 22. Melkersson, Kristina I.
    et al.
    Scordo, Maria Gabriella
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Gunes, Arzu
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Dahl, Marja-Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Impact of CYP1A2 and CYP2D6 polymorphisms on drug metabolism and on insulin and lipid elevations and insulin resistance in clozapine-treated patients2007In: Journal of Clinical Psychiatry, ISSN 0160-6689, E-ISSN 1555-2101, Vol. 68, no 5, p. 697-704Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Adverse metabolic effects of atypical antipsychotics have increasingly been recognized. Recently, we found that levels of insulin and triglycerides increased by increasing serum clozapine concentration in clozapine-treated patients. As these insulin and triglyceride elevations probably are drug concentration-dependent, they also would be expected to be drug metabolism-related. The genetically polymorphic cytochromes P450 CYP1A2 and CYP2D6 catalyze the metabolism of clozapine. The aim of this study was to evaluate the impact of CYP1A2 and CYP2D6 polymorphisms on serum drug and metabolite levels and on insulin and triglyceride elevations and insulin resistance in patients receiving clozapine. METHOD: Seventeen clozapine-treated patients were genotyped for CYP1A2 and CYP2D6 by polymerase chain reaction-based methods. Serum concentrations of clozapine and its N-desmethylmetabolite, blood glucose, and serum levels of insulin, C-peptide, triglycerides, and cholesterol were analyzed, and homeostasis model assessment index for insulin resistance (HOMA-IR) was determined. RESULTS: Clozapine and N-desmethylclozapine concentration-to-dose (C/D) ratios were significantly higher in patients carrying 2 CYP1A2 single nucleotide polymorphisms (SNPs), previously suggested to cause low enzyme activity, compared to those with no such SNPs (p < .05). In contrast, clozapine and N-desmethylclozapine C/D ratios were not related to the CYP2D6 genotype. Furthermore, patients with elevated insulin levels more frequently carried CYP1A2*1C and/or *1D alleles, had higher clozapine and N-desmethylclozapine C/D ratios, and had higher lipid levels and HOMA-IR, compared to patients with normal insulin levels (p < .05). CONCLUSION: CYP1A2 variants *1C and *1D seem to be associated with higher serum clozapine concentrations and an increased risk of developing insulin and lipid elevations and insulin resistance on a given dose of clozapine.

  • 23. Ozdemir, V
    et al.
    Gunes, Arzu
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Dahl, Marja-Liisa
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Scordo, Maria Gabriella
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Williams-Jones, B
    Someya, T
    Could endogenous substrates of drug-metabolizing enzymes influence constitutive physiology and drug target responsiveness?2006In: Pharmacogenomics, ISSN 1462-2416, Vol. 7, no 8, p. 1199-1210Article in journal (Refereed)
  • 24. Panagiotidis, Georgios
    et al.
    Arthur, Holger W.
    Lindh, Jonatan D.
    Dahl, Marja-Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sjöqvist, Folke
    Depot haloperidol treatment in outpatients with schizophrenia on monotherapy: impact of CYP2D6 polymorphism on pharmacokinetics and treatment outcome2007In: Therapeutic Drug Monitoring, ISSN 0163-4356, E-ISSN 1536-3694, Vol. 29, no 4, p. 417-422Article in journal (Refereed)
    Abstract [en]

    Haloperidol and several other antipsychotic drugs are at least partially metabolized by the polymorphic cytochrome P450 2D6 (CYP2D6). The interindividual variation in metabolic capacity of CYP2D6 might be of importance when dosing. In this study, 26 outpatients with schizophrenia and depot haloperidol as monotherapy were genotyped. The authors found 1 patient with no functional alleles, 8 with one functional allele, 16 with two functional alleles, and 1 with three functional alleles. The daily dose of haloperidol ranged from 0.45 to 14.29 mg. Steady state plasma concentrations were measured at peak (range, 1.6-67 nmol/L) and at trough (range, 1.0-49 nmol/L). The Positive and Negative Syndrome scale for Schizophrenia and the Extrapyramidal Symptom Rating Scale were used to evaluate the clinical effect. The authors found a clear correlation between haloperidol plasma concentration and number of active CYP2D6 alleles. No correlation was found between plasma concentration of haloperidol or number of CYP2D6 alleles and treatment outcome or side effects. A model to predict plasma concentration from dose and number of active CYP2D6 alleles was formed from the obtained data by means of multiple linear regression.

  • 25. Pelkonen, O
    et al.
    Dahl, Marja-Liisa
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Farmakogeneettiset yksilövaihtelut.2002In: Kliininen farmakologia ja lääkehoito., 2002, p. 63-Chapter in book (Other scientific)
  • 26.
    Scordo, Maria Gabriella
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Aklilu, E
    Yasar, U
    Dahl, Marja-Liisa
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Spina, E
    Ingelman-Sundberg, M
    Genetic polymorphism of cytochrome P450 2C9 in a Caucasian and a black African population.2001In: Br J Clin Phamacol, Vol. 52, p. 447-Article in journal (Refereed)
  • 27.
    Scordo, Maria Gabriella
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Dahl, Marja-Liisa
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Spina, Edoardo
    Cordici, Francesco
    Arena, Maria Grazia
    No association between CYP2D6 polymorphism and Alzheimer's disease in an Italian population.2006In: Pharmacol Res, ISSN 1043-6618, Vol. 53, no 2, p. 162-5Article in journal (Refereed)
  • 28.
    Scordo, Maria Gabriella
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Spina, E
    Romeo, P
    Dahl, Marja-Liisa
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Bertilsson, L
    Johansson, I
    Sjoqvist, F
    CYP2D6 genotype and antipsychotic-induced extrapyramidal side-effects in schizophrenic patients.2000In: Eur J Clin Pharmacol, Vol. 56, p. 679-Article in journal (Refereed)
  • 29.
    Scordo, Maria Gabriella
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Klinisk farmakologi.
    Spina, Edoardo
    Dahl, Marja-Liisa
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Klinisk farmakologi.
    Gatti, G
    Perucca, Emilio
    Influence of CYP2D6, 2C19 and 2C9 genetic polymorphisms on the steady state plasma concentrations of the enantiomers of fluoxetine and norfluoxetine2005In: Basic & Clinical Pharmacology & Toxicology, Vol. 97, p. 296-301Article in journal (Refereed)
  • 30. Sim, Sarah C
    et al.
    Risinger, Carl
    Dahl, Marja-Liisa
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Aklillu, Eleni
    Christensen, Magnus
    Bertilsson, Leif
    Ingelman-Sundberg, Magnus
    A common novel CYP2C19 gene variant causes ultrarapid drug metabolism relevant for the drug response to proton pump inhibitors and antidepressants.2006In: Clin Pharmacol Ther, ISSN 0009-9236, Vol. 79, no 1, p. 103-13Article in journal (Refereed)
  • 31. Tomson, T
    et al.
    Dahl, Marja-Liisa
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Kimland, E
    Therapeutic monitoring of antiepileptic drugs for epilepsy.2007Report (Other scientific)
  • 32. Varsaldi, Federica
    et al.
    Miglio, Gianluca
    Scordo, Maria Gabriella
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Dahl, Marja-Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Villa, Laura Maria
    Biolcati, Aldo
    Lombardi, Grazia
    Impact of the CYP2D6 polymorphism on steady-state plasma concentrations and clinical outcome of donepezil in Alzheimer's disease patients2006In: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 62, no 9, p. 721-726Article in journal (Refereed)
    Abstract [en]

    Objective: The aims of this study were to evaluate the impact of the CYP2D6 polymorphism on both the steady-state plasma concentrations (Cp) and the clinical outcome of donepezil, a selective acetylcholinesterase inhibitor used in the treatment of Alzheimer's disease (AD). Methods: Forty-two patients of Caucasian ethnicity affected by probable AD were included in the study. All had been receiving therapy with donepezil for at least 3 months: 31 patients with 5 mg/day and 11 patients with 10 mg/day. The CYP2D6 genotype was analysed, and donepezil Cp was measured by using high-performance liquid chromatography. Results: On the basis of their CYP2D6 genotype, 30 patients could be classified as homozygous extensive metabolizers (EM), 10 as heterozygous EM and 2 as ultrarapid metabolizers (UM). No poor metabolizer was found. The dose and body weight-corrected median donepezil Cp were slightly, though not significantly, lower in homozygous than in heterozygous EM (0.33 vs. 0.41 ng/ml/mg/kg, respectively). The latter group consistently showed a better clinical response to treatment, as measured by change in Mini-Mental State Examination score (median: 1.40 vs. -1.30, respectively). UM patients had lower Cp than EM patients and showed no clinical improvement. Conclusions: Our preliminary data suggest that the CYP2D6 polymorphism influences both donepezil metabolism and therapeutic outcome and that a knowledge of a patient's CYP2D6 genotype together with donepezil concentration measurements might be useful in the context of improving the clinical efficacy of donepezil therapy.

  • 33. Wåinder, Jan
    et al.
    Prochazka, Jiri
    Oden, Anders
    Sjödin, Ingemar
    Dahl, Marja-Liisa
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Ahlner, Johan
    Bengtsson, Finn
    Mirtazapine naturalistic depression study (in Sweden)--MINDS(S): clinical efficacy and safety.2006In: Hum Psychopharmacol, ISSN 0885-6222, Vol. 21, no 3, p. 151-8Article in journal (Refereed)
  • 34. Yamada, H
    et al.
    Dahl, Marja-Liisa
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Viitanen, M
    Winblad, B
    Sjöqvist, F
    Lannfelt, L
    No association between familial Alzheimer disease and cytochrome P450 polymorphisms.1998In: Alzheimer Dis Assoc Disord, ISSN 0893-0341, Vol. 12, no 3, p. 204-7Article in journal (Refereed)
1 - 34 of 34
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