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Clinical Biochemistry/Toxicology Test Description Address to send samples Consultant Scientist Laboratory Contact LC-MS/MS Plasma Tyrosine Kinase Inhibitor (TKI) Assay Service Toxicology Unit Department of Clinical Biochemistry Third Floor, Bessemer Wing King’s College Hospital Denmark Hill London SE5 9RS Background Prof R J Flanagan Tel: 020 3299 5824 e-mail: [email protected] Mr Simon Handley Tel: 020 3299 5881/2 Fax: 020 3299 5888 Direct e-mail: [email protected] Toxicology lab e-mail: [email protected] An assay request form is available from our website (www.kingspath.co.uk) or from the Toxicology Unit. Sample required Collect blood into tube containing EDTA and mix well (do not shake). ‘Trough’ samples are preferred, either pre-dose, or in the morning after an evening dose (once daily dosing). Whole blood samples to be sent by first class post on the day of collection, or send plasma within 48 h of collection. Reporting results Secure electronic results transmission available to all users with NHS net access. Clinicians wishing to use this unique, free and secure Results On-Line service should contact Pathology IT via e-mail [email protected] or telephone 020 3299 4829 for details. Conventional results notification by post or fax available. Laboratory accreditation Turnaround Time Cost KingsPath & GSTS provide a high quality clinical diagnostic service, offering one of the most comprehensive specialist pathology test portfolios in the UK across all pathology disciplines : Biochemistry, Haematology, Histopathology, Immunology, Microbiology & Virology. Our recent major re-development programme included investment in a state-ofthe-art Blood Sciences Laboratory on our King’s College Hospital site, one of the largest integrated automated laboratories in Europe. For more information about our full range of specialist tests , consult our websites at www.kingspath.co.uk and www.gsts.com. We are part of King’s Health Partners, one of the UK’s first Academic Health Sciences Centres. CPA accreditation. External quality control of imatinib/ norimatinib, dasatinib and nilotinib assays (Chromsystems). All assays carried out to Good Laboratory Practice (GLP) standards. Results are normally available within 3-4 working days of sample receipt. Tyrosine kinase inhibitors (TKIs) are used in the treatment of haematological and other malignancies. TKIs are administered orally and their bioavailability is thus dependent on gastrointestinal absorption and first-pass metabolism. In addition, they are metabolised by hepatic cytochrome P450 enzymes, the activity of which may be subject to large inter-individual variation and may be influenced by a number of factors such as drug-drug interactions, food intake, and smoking habit. Moreover, some TKIs are substrates of drug transporters, i.e. efflux pumps and uptake pumps, and are extensively (> 90 %) bound to plasma protein. Finally, some TKIs are capable of inhibiting their own transporters and metabolising enzymes, making their disposition and metabolism at steady-state difficult to predict. A given dose can therefore yield significantly different plasma concentrations in different patients, favouring the selection of resistant clones in the case of sub-therapeutic drug exposure and increasing the risk of toxicity if dosage is excessive. Therapeutic drug monitoring (TDM), i.e. the measurement of plasma concentrations of the parent drugs and sometimes of plasma metabolites therefore has a role in assessing adherence and optimising dosage. Clinical Application Poor/non-response, primary treatment failure. Development of treatment resistance. Assessing adherence and dose monitoring/optimisation. Investigation of possible drug-drug interactions and dose-related adverse effects. On application Quality Accreditations All our laboratories are accredited to CPA standards and JACIE standards where applicable. Our pathology services are regulated and licensed by the Human Tissue Authority (HTA) and the Medicines and Healthcare products Regulatory Agency (MHRA). Electronic KingsPath Results On-Line Clinicians with NHS net access wishing to use our unique, free and secure Results On-Line service should e-mail [email protected] or telephone 020 3299 4829 for details. For more information on how we can support all your specialist & routine pathology needs, consult our websites, contact Customer Liaison Manager Adrian Turner on 020 3299 1741, or E-mail [email protected] High quality, clinically excellent, cost effective pathology services. GSTS Pathology St. Thomas’ Hospital, Westminster Bridge Road, London SE1 7EH www.gsts.com KingsPath King’s College Hospital, Denmark Hill, London SE5 9RS www.kingspath.co.uk Version 1.0 September 2012 Fast Turnaround Time, Results Online Minimal specimen requirement (2 mL EDTA blood, pre-dose sample). Results normally available on-line within 3-4 days of sample receipt. Advice on interpretation of results for imatinib and norimatinib, dasatinib, and nilotinib provided in conjunction with the Department of Haematological Medicine, King’s College Hospital. Clinical Biochemistry/Toxicology Tyrosine Kinase Inhibitors (TKIs) Referral Form Dasatinib, Erlotinib, Gefitinib, Imatinib/norimatinib, Lapatinib, Nilotinib, Sorafenib, Sunitinib Tyrosine Kinase Inhibitors (TKIs) Tyrosine Kinase Inhibitors In Plasma Synonyms/Keywords