Creative Biolabs has worked extensively on a wide variety of ADME assays. As part of our in vitro ADME service, we provide drug distribution evaluation service to meet your demands.

Drug distribution describes the reversible movement of a drug from one location to another within the body. Usually, it refers to a drug transfer from the blood to various tissues. Theoretically, each part of the body can receive different doses of the drug and remain the drug in the different amount of time.

The distribution of a drug in the body depends on many factors. For instance, a drug's physicochemical characters, like lipophilicity and aqueous solubility, depend whether a drug tends to stay in fluid tissue (like blood and intercellular substance) or lipid tissue (like fat). Permeability is another factor that affects distribution. A drug has different penetration abilities to cross different tissue membranes which lead to the different volume of distribution. Tissue and plasma protein binding is the third factor. If a drug binds to proteins circulating in the blood tightly, it's hard to leave the bloodstream and enter tissues. Some drugs accumulate in certain tissues as tightly drug binding and prolong the effect of the drug and drug accumulation.

Drug Distribution Figure1. Distribution of plasma protein binding (percentage protein bound) in different therapeutic areas (Kratochwil et al. 2002)

Creative Biolabs provides the following services to help our customers evaluate drug distribution.

Plasma Protein Binding

Proteins in blood can greatly influence the drug distribution in tissues. They influence a drug distributes from blood into tissues as well as from tissues to action sites. Only drugs that are unbound to components in the blood are free to diffuse across the cell membranes into the action sites. Creative Biolabs performs three “gold standard” methods for PPB evaluation which include equilibrium dialysis, ultrafiltration and ultracentrifugation. We provide 3 different plasma concentrations (10% plasma, 50% plasma and 100% plasma) to perform the PPB evaluation depending on your budget and compound characteristics. LC-MS/MS quantification is used to analyze the results.

Blood Plasma Partitioning

Knowledge of blood to plasma ratio is important to understanding and predicting the concentration of a drug in blood. Creative Biolabs provides blood to plasma ratio determination service to understand drug distribution in red blood cells and plasma. Test drug is spiked into fresh heparinized whole blood, reference red blood cells and reference plasma. Fractions of each part are analyzed by LC-MS/MS.

Brain Tissue Binding

Assessment of brain unbound concentration (Cu, brain) is crucial in understanding the PK and PD of CNS drugs, as only the unbound drug is free to diffuse across the BBB into the action sites. In case of that, Creative Biolabs provides a high throughput brain tissue binding assay to deliver a value of fraction of compound unbound to brain tissue (fu, brain). Our brain tissue binding assay is fully developed to use a 96-well equilibrium dialysis unit for quickly and accurately determining the unbound fraction of drugs in brain tissue. The results are calculated by LC-MS/MS.

Microsomal Binding

Measurement of the affinity of a drug to microsomal allows the accurate estimation of in vivo pharmacokinetics and drug-drug interactions by correcting the experimental clearance with the extent of binding to microsomes. Creative Biolabs provides kinetic measurements using liver microsomes to predict in vivo metabolic clearance of compounds in humans.

For more detailed information, please feel free to contact us or directly sent us an inquiry.

Reference

  1. Kratochwil NA, Huber W, Müller F, et al. (2002) “Predicting plasma protein binding of drugs: a new approach” Biochemical Pharmacology 64(9): 1355–1374

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