Publications (42) View all
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Article: Therapeutic drug monitoring for tomorrow.
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ABSTRACT: Therapeutic drug monitoring (TDM) represents an early approach to personalised medicine. It helps the clinician to individualise drug treatment and guide dosage to reach systemic drug concentrations associated with therapeutic efficacy and/or to reduce the risk of concentration-dependent adverse effects. Well into the fifth decade of TDM as a service to healthcare, this concept is still expanding, and new areas for clinical implementation continue to emerge. The aim of this overview is to discuss promising new therapeutic areas in future TDM services, how to improve the clinical interpretation of single drug measurements and how recent technology development opens the doors to research and new applications.European Journal of Clinical Pharmacology 05/2013; 69 Suppl 1:25-32. · 2.85 Impact Factor -
Article: CYP2D6 and adjuvant tamoxifen: possible differences of outcome in pre- and post-menopausal patients.
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ABSTRACT: Aim: Previous studies on CYP2D6 activity and the effect of adjuvant tamoxifen in breast cancer are inconsistent. We analyzed the impact of the CYP2D6 polymorphism in pre- and post-menopausal patients that were adherent to tamoxifen treatment for at least a year. Materials & methods: A total of 382 breast cancer patients prescribed adjuvant tamoxifen for 5 years constituted the study-base. Clinical information, including compliance and outcome, was retrieved from medical records. Comprehensive CYP2D6 genotyping was performed and translated into predicted metabolic activity. Results & conclusion: In patients adherent to tamoxifen for at least one year (n = 313) there was an association between reduced CYP2D6 activity (≤50% of normal) and recurrence (p = 0.025) and breast cancer-specific mortality (p = 0.034). In a multivariable analysis, CYP2D6 remained an independent predictor of outcome. In a subgroup analysis, the effect of CYP2D6 seemed to derive mainly from premenopausal patients, which represents a new finding that needs validation in a larger study sample. Original submitted 13 November 2012; Revision submitted 1 March 2013.Pharmacogenomics 04/2013; 14(6):613-22. · 3.97 Impact Factor -
Article: Serum Levels of 25-hydroxyvitamin D and the CYP3A Biomarker 4β-hydroxycholesterol in a High-dose Vitamin D Supplementation Study.
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ABSTRACT: The primary aim was to study the relationship between individual serum levels of 25-hydroxyvitamin D and 4β-hydroxycholesterol, which is an endogenous biomarker of the drug-metabolising CYP3A enzymes. In addition, the relationship between this biomarker and inflammation, measured as C-reactive protein (CRP), was investigated. Serum samples were used from a recently performed clinical trial in patients with antibody deficiency or increased susceptibility to respiratory tract infections that were randomised to either placebo or high dose (4000 IU/day) vitamin D for 12 months. 116 patients were included in the final analyses and serum samples collected 6 months after study start were analysed. At this time point, 25-hydroxyvitamin D levels were found to range between 10-284 nmol/ L. Individual levels of 25-hydroxyvitamin D as well as CRP were compared with 4β-hydroxycholesterol levels. In addition, all participants were genotyped for two polymorphisms (Taq1 and Foq1) in the vitamin D receptor gene (VDR). There was no significant correlation between individual serum levels of 25-hydroxyvitamin D and 4β-hydroxycholesterol. However, a moderate, but statistically significant, negative correlation between CRP and 4β-hydroxycholesterol levels was observed. This study in patients with highly variable serum levels of 25-hydroxyvitamin D could not reveal any relationship between vitamin D and 4β-hydroxycholesterol, an endogenous biomarker of CYP3A activity. However, the negative correlation between CRP and 4β-hydroxycholesterol supports earlier experimental results that inflammation may suppress hepatic CYP3A activity, a finding of potentially high clinical relevance that warrants further exploration.Drug metabolism and disposition: the biological fate of chemicals 02/2013; · 3.74 Impact Factor -
Article: Institutional Profile: Karolinska Institutet.
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ABSTRACT: Research in pharmacogenomics has been intensive at Karolinska Institutet (KI) for approximately 25 years. Initial initiatives were focused on the identification and characterization of novel CYP2D6 alleles causing ultrarapid or defective drug metabolism. Such discoveries were possible owing to the early implementation of therapeutic drug monitoring and the access to individuals phenotyped with respect to drug metabolism. The translational work at KI has been of utmost importance for successful research, including functional characterization and clinical validation of allelic variants in drug metabolism, as well as discoveries of novel polymorphisms, recent examples being the CYP2C19 and UGT2B17 genes. The clinical pharmacology laboratory at KI campus Huddinge is one of the leading sites for therapeutic drug monitoring in northern Europe and obtains an increasing number of clinical requests, also important for pharmacogenetic research. Furthermore, the recently opened Center for Hematology and Regenerative Medicine, with a clear translational emphasis, offers an opportunity for studying drug metabolism and toxicity in vitro by use of human hepatocytes.Pharmacogenomics 12/2012; 13(16):1887-1891. · 3.97 Impact Factor -
Article: Influence of the CYP2C9*3 allele on the pharmacological interaction between warfarin and simvastatin: author reply.
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ABSTRACT: A letter in response to: Botton MR, Hutz MA & Suarez-Kurtz G. Influence of the CYP2C9*3 allele on the pharmacological interaction between warfarin and simvastatin. Pharmacogenomics 13(14), 1557-1559 (2012).Pharmacogenomics 11/2012; 13(14):1561-1562. · 3.97 Impact Factor
