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Vast experience in toxicokinetic analysis and reporting to OECD guidelines. Provision of GLP-compliant toxicokinetic report appendices in association with Independent Quality Assurance and Quality Control units.
Scaling pharmacokinetic parameters (e.g. intrinsic clearance) from in vitro studies (human hepatocytes/microsomes) to those in man.
Allometric scaling to predict pharmacokinetic parameters in man from animal studies; enabling identification of compounds with potential high clearance and optimise dose selection for first-in-man studies. This type of analysis also enables selection of appropriate limits of quantification for bioanalysis.
Deconvolution and In Vitro/In Vivo Correlations
Deconvolution is a procedure by which the input (absorption) process of a compound following various routes of administration (e.g., oral, inhalation, ocular) is dynamically characterised. This technique has highlighted selective uptake and release from the liver and differentiated absorption from the lungs for various inhalation devices.
Extensive expertise in supporting first-into-man studies including pharmacokinetically-guided dose escalation. Provision of "fast turn-around" interim PK summaries to assist dose escalation and enable optimal assessment of maximum tolerated dose. Selection and fitting of models to single-dose PK data to provide predictions of systemic exposure for different dose regimens (e.g. selection of appropriate multiple dose regimen, loading dose to achieve immediate steady state or different administration routes).
Statistical analysis of PK parameters derived from Phase I studies, including assessment of bioavailability/bioequivalence, effect of food/age/sex, dose proportionality, drug-drug interactions, and renal-impairment. Fully conversant with FDA guidelines.
Experience in fitting logistic, Emax, inhibitory and direct-response models, including the development of effect-distribution models using link models and also simultaneous fitting of concentration-effect data. PK/PD models provide important information for the selection of dose regimens for Phase II/III studies.
Protocol Design/Report Writing
Consultation services on experimental design and clinical Phase I/II protocols. Generation of Pharmacokinetic Analysis Plans and concise, comprehensive reports of high quality that integrate PK, PD and associated statistical analysis. Publication of manuscripts in reputable journals and contribution to Expert Reports for regulatory submissions.
Charlie Brindley has over 25 years experience in non-clinical and clinical pharmacokinetics working in the Pharmaceutical industry and CROs and has over 30 publications on PK and PK-PD in reputable journals.
KinetAssist was established in March 2006 and is a member of the UK GLP Compliance programme. KinetAssist writes around 20 GLP-compliant toxicokinetic/pharmacokinetic reports each year.
KinetAssist also specializes in deconvolution and Phase I clinical PK support.
Pharmacokinetic analyses are undertaken using WinNonlin (fully validated system). Analysis and reporting is carried out within a fully audited Quality Management System.
Chairman of the Toxicokinetic Discussion Group (TKDG)
MHRA UK GLP Compliance Programme Member
- Oct 1982 - Dec 1985 Post-Doctoral Research, Charing Cross Hospital, London, UK
- Jan 1986 - Sep 1989 Senior Clinical Pharmacokineticist Hoffman-La Roche, Basel, Switzerland
- Oct 1989 - Oct 1993 Senior Pharmacokineticist, Huntingdon Research Centre, Cambridgeshire, UK
- Oct 1993 - 2005 Director of Pharmacokinetics, Drug Metabolism and Pharmacokinetics, Quintiles Ltd, Edinburgh, UK (formerly Syntex Research Centre)
- 2005 - March 2006 Director of Pharmacokinetics, Drug Metabolism and Pharmacokinetics, Aptuit (Edinburgh) Ltd, UK (formerly Quintiles Limited). Managing Pharmacokinetic & Pharmacodynamics Group of 9 Pharmacokineticists/Biostatisticians
- April 2006 - Present Director of KinetAssist Limited. Pharmacokinetic Consultation and Services
TAN T, FIELD B, MINNION S, CUENCO-SHILLITO J, CHAMBERS E, ZACVARGHESE S, BRINDLEY C, MT-ISA S, FLORENTINO F, ASHBY D, WARD I, GHATEL M, BLOOD S. Pharmacokinetics, adverse effects and tolerability of a novel analogue of human pancreatic polypeptide, PP 1420. Br. J. Clin. Pharmacol.2011, 73:232-239 http://www.ncbi.nlm.nih.gov/pubmed/21834938
AUSTIN S, BRINDLEY C, KAVAKLI K, NORTON M, SHAPIRO A. Pharmacokinetics of a high-purity plasma-derived factor X concentrate in subjects with moderate or severe hereditary factor X deficiency. Haemophilia 2014, 22:426-432.
CHARRON, CATHERINE; RUSSELL, PAUL; ITO, KAZUHIRO; LEA, SIMON; KIZAWA, YASUO; BRINDLEY, CHARLIE; SINGH, DAVE. RV568, a narrow spectrum kinase inhibitor with p38 MAPK and selectivity, suppresses COPD inflammation. Eur. Respiratory J. 2017, 50:1700188