Download Tyrosine Kinase Inhibitors (TKIs) Plasma Tyrosine Kinase Inhibitor

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