Pharmidex

The Challenge

Understanding the risks surrounding physicochemical properties, dose, linearity, drug interactions, induction, polymorphic drug metabolism, reactive metabolism from start to finish, is a major challenge in the costly and time consuming drug discovery process.
Pharmidex offers a full service to understand the link between drug levels and effect in preclinical animal models (PK-PD) while balancing ADMET/PK properties, aiding in the selection of the most appropriate drugs for clinical evaluation.

The Solution

Pharmidex provides an extensive range of ADMET technologies aimed at optimising potential new medicines  for drug development risks using both preclinical and human prediction data. Together with a wealth of knowledge and experience in CNS, CV, respiratory and inflammatory discovery programmes, Pharmidex can aid more rapid progression and improvement in the probability of success of potential new medicines.

In Vitro

Physico-chemical  properties

• LogD
• Solubility in PBS or biological fluids
• Stability in PBS or biological fluids

Metabolic  stability

• Metabolic stability in liver microsomes, S9 fraction
• Metabolic stability in cryopreserved hepatocytes
• Metabolic stability in other tissues and fluids (as % turnover, half life or intrinsic clearance)

Blood distribution and protein binding

• Plasma protein binding - human & most species
• Blood partitioning - human & most species
• Tissue partitioning human & most species
• Blood to brain partitioning - human & most species (fraction unbound)

Cell Permeability and transporter interactions

• Cell permeation - passive and Pgp mediated (MDR/MDCK)

CYP  interactions

• Inhibition in singly-expressed human P450 inhibition
• Inhibition of Human P450 in microsomes (probe drugs via LC-MS/MS)
• Time dependent inhibition of human P450s
• Induction- Human P450 induction in hepatocytes
• Reaction Phenotyping -Human P450  isoform specific metabolism reactive metabolism glutathione trapping
• Metabolite identification in biological samples

In Vivo

Pharmacokinetics, bioavailability & scaling

• PK profiling in preclinical species
• PK profiling in cannulated pre-clinical species
• Repeat PK profiling in pre-clinical species PK scaling to humans
• Wide selection of dosing and sampling routes
• Bolus/infusion and other perenteral dosing routes

Toxicokinetics

• Repeat dosing in preclinical species
• Dose range studies

Absorption, distribution, metabolism and excretion

• PK profiling in cannulated animals -
• Hepatic portal vein
• Bile duct
• In situ perfusion studies (liver, brain)
• Dual and triple cannulation studies in range of blood vessels
• Metabolite identification in biological fluids

Radiolabelled ADME studies

• Excretion balance studies
• Drug and metabolite profiling
• Metabolite identification

Efficacy and side-effect profiling

• Telemetry
• CNS side-effects (LMA)
• Neurochemicals in brain regions (microdialysis)

Drug distribution studies

• Tissue distribution of total or free drug levels (microdialysis)
• Free drug level measurements in various brain regions (microdialysis)

PKPD modelling

• PKPD modelling - preclinical to clinical extrapolation