Pharmacokinetics & Metabolism

Assessment of the absorption, distribution, metabolism and excretion properties of a compound (ADME) is essential during the process of drug development. At Active Biotech we are very experienced in designing and performing most kinds of ADME studies needed to support research and development of new drugs. We work from early phase with in vitro techniques as well as with pharmacokinetics and metabolism in animal models and in clinical phases. Within the fields stated below we can offer service regarding study design, experimental performance, evaluation and reporting:

In Vitro ADME

• In vitro metabolism
  In our laboratories, we perform a wide range of metabolism studies using hepatocytes, microsomes and other sub cellular fractions from various species including human, as well as with recombinant enzymes. Among the studies we perform are:
  - Metabolic stability and metabolite identification (for further information, see Analytical chemistry)
  - Cytochrome P450 isoform profiling
  - Drug-drug interaction
• In vitro permeability
  In our cell laboratories we use cultured Caco-2 cells for permeability studies. With specific substrates and inhibitors we also use the Caco-2 cells for studies on drug interactions with the P-gp transporter.
• Plasma protein binding
  We perform protein binding in plasma from various species using the ultrafiltration and/or equilibrium dialysis technique. The binding to specific plasma proteins, e.g. albumin or α1-acid glycoprotein, can also be studied with the same techniques.

In vitro studies in microplate format.

Pharmacokinetics and metabolism in animals and man

Our experienced pharmacokinetic group can assist in all phases of clinical and pre-clinical pharmacokinetic assessment. Our laboratory is well equipped with chromatographic systems, flow scintillators, oxidizer and liquid scintillation analyzers. We perform non-compartmental as well as compartmental analyses including biostatistics, using WinNonlin and NONMEM. We can provide our customers with high quality, regulatory compliant reports if required. Active Biotech can offer services on the following pharmacokinetic studies:

• In vivo animal studies
  
  • Pharmacokinetic evaluation
  • Toxicokinetic evaluation
  • Mass balance and metabolism using radio labeled compound
  • Tissue distribution and excretion of radio labeled compounds analyzed by combustion and scintillation or WBA (for further information see Autoradiography).
  • Metabolite identification (for further information, see Analytical chemistry)
  • Dose simulation

• Clinical pharmacokinetics
  
  • Pharmacokinetic evaluation in various clinical studies such as microdose, bioequivalence, drug-drug interactions and food interaction
  • Mass balance and metabolism using radio labeled compounds
  • Metabolite identification (for further information, see Analytical chemistry)
  • Simulation of plasma profiles at different dosage regimens
  • Design of clinical protocols

Predicted plasma concentration time profile during ten days of daily administration (light blue) together with the single dose profile (red) and the profile after daily administrations including a loading dose at time 0.5  (dark blue).