Toxicokinetics

Vast experience in toxicokinetic analysis and reporting to OECD guidelines. Provision of toxicokinetic/pharmacokinetic report appendices in association with Independent Quality Assurance and Quality Control units.

Scaling

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 (see "Deconvolution").

Evaluation of in vitro / in vivo dissolution correlations (IVIVC) for modified-release drug formulations. Establishing an IVIVC assists pharmaceutical development and can avoid formal bioequivalence studies.

First-In-Man/Phase I

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.

Pharmacokinetic/Pharmacodynamic Modelling

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 (e.g. see "Deconvolution") and contribution to Expert Reports for regulatory submissions.