DMPK/ADME

ADME and DMPK are integral to drug discovery. DMPK/ADME testing contributes to the optimization of new chemical entities in drug discovery by balancing properties related to drug gastrointestinal absorption (for orally administered therapies), distribution, clearance, elimination and DDI potential as quickly and cost-effectively as possible. BOC Sciences, an industry-leading clinical trial laboratory service, offers a wide range of ADME screening and DMPK services, using validated bioanalytical methods to support the identification and characterization of drug candidates, providing researchers with important insights into drug behavior to determine which drug candidates to explore further.

Introduction

• ADME

ADME, toxic pharmacokinetics, refers to the absorption, distribution, metabolism and excretion processes of exogenous chemicals in the body. The optimization of ADME (absorption, distribution, metabolism and excretion) properties of drug molecules is one of the most difficult aspects of the entire drug discovery process, and the analysis of ADME properties plays a key role in the success of drug development.

Possible manifestations of poor ADME properties of drug candidates

• Increasing the dose does not increase the serum concentration of the drug - absorption problem
• Appropriate drug concentration in serum but little distribution in brain - Active efflux
• Repeated dosing with reduced serum concentrations - induced enzyme activity
• Increased blood concentration when coadministered with other drugs - inhibition of enzyme activity
• Duration of action does not correspond to half-life - active metabolite production or too slow dissociation from target

• DMPK

DMPK, drug metabolism and pharmacokinetics, is a very important link in the new drug development chain and plays an important role in improving the efficiency of new drug development.

Drug-ideal DMPK properties

• Complete absorption (passive absorption is preferred), bioavailability >50% and low variability.
• AUC is proportional to dose and PK/PD correlation is clear.
• Rapid arrival at the target organ and no accumulation outside the target organ.
• PPB<90%, independent of concentration and time.
• Plasma clearance CL<30% Qh, cleared by multiple routes.
• Age, race, gender, disease state, etc. have little effect on CL.
• Low amount of metabolites, no reactive metabolites are produced.
• Does not inhibit or induce major drug metabolizing enzymes and transporter proteins, and is not affected by food.
• Human T1/2>6hr, which facilitates the reduction of dosing frequency and improves adherence.

Types of early DMPK studies

• Metabolite screening and identification: in vitro, in vivo, GSH Trapping.
• Metabolic stability: microsomes, S9, hepatocytes, plasma, whole blood.
• Protein binding: plasma, brain tissue, microsomal proteins, FBS; erythrocyte plasma distribution ratio.
• Permeability and transport: Caco-2, MDCK-MDR1/BCRP, OATs/OCTs/OATPs.
• In vitro metabolic DDI: P450 inhibition/TDI, P450 induction/PXR, metabolic enzyme phenotypes.
• In vivo PK: multiple genera, multiple modes/routes of administration; continuous/crossover/single-point blood collection; BBB (homogenate/CSF), tissue distribution; excretion (BDC), DDI in vivo.

BOC Sciences' DMPK/ADME Services

Advantages of BOC Sciences

• Rich experience, flexibility and timeliness
• PK/PD one-stop service
• State-of-the-art bioanalytical laboratory
• Fast project turnaround time
• Cost-effectiveness

BOC Sciences is committed to being a good partner to our global clients. If you are interested in what we can offer, please feel free to contact us and get a quote.