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Absorption, Distribution, Metabolism, and Excretion
One of the major areas in which HD Biosciences serves the pharmaceutical industry is drug absorption, distribution, metabolism and excretion (ADME). We have estabolished state-of-the-art bioanalytical facilities. The scientific staff that oversees these operations is very
experienced in ADME. Our goal is to fully serve the clients in fulfilling their ADME needs.
Bidirectional Caco-2 Cell Permeability, Pgp Substrate or Inhibitor Identification
Bidirectional Caco-2 Cell Permeability, Pgp Substrate and Inhibitor Identifications
Caco-2 cell permeability (Papp) provides the data to predict absorption of drug candidates across the intestinal epithelial cell barrier. This assay has been validated and confirmed as a robust assay for assessing compound permeability, identification of Pgp (P-glycoprotein)
substrates or Pgp inhibitors.
Protein Binding
Plasma protein binding can greatly influence the tissue distribution, clearance, and pharmacological effects of drugs. HD Biosciences performs discovery stage plasma protein binding assays, as well as more thorough studies for regulatory submissions and clinical samples, using equilibrium dialysis or ultrafiltration. Analysis of protein binding samples is
typically performed using LC/MS/MS.
Plasma Stability
In vitro plasma stability provides valuable information prior to in vivo PK testing. The samples containing test articles are incubated at 37oC for different time periods. Analysis
of plasma stability samples is performed using LC/MS/MS.
Blood Cell Partitioning
The blood¨Cto-plasma concentration ratio of test article is determined in fresh mouse, rat, dog, monkey, and human blood. Percent blood cell distribution is calculated based on the blood and plasma concentrations and hematocrit. Analysis of samples is performed using
LC/MS/MS.
In Vitro Metabolism
We provide a full range of in vitro and ex vivo assays utilizing microsomes, S9 fractions, or primary hepatocytes from multiple species, to study drug metabolism. Microsomal stability is commonly used as a discovery tool to predict the extent of hepatic first-pass metabolism. At later stages, it is important to minimize the potential of clinical drug-drug interactions between drug candidates and co-medications. The CYP inhibition potential of new drug candidates can be assessed using a rapid, reliable, and specific CYP inhibition screening method. This method measures the activities of seven major human CYP isozymes (CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, and 3A4) using selective substrates incubated with human liver microsomes and hepatocytes or using recombinant CYP
isozymes and fluorescence method for high-through-put screening.
Service Offerings:
Metabolic stability and half-life determination
High throughput cocktail CYP450 IC50 assay
CYP450 isozyme inhibition
CYP450 isozyme phenotyping
Time-dependent inhibition
CYP450 induction
Reactive-intermediate trapping
Metabolite identification
We are routinely utilizing the strengths of bioanalysis, LC/MS/MS, and NMR for metabolite identification studies. The goal is to define metabolic pathways for new drug candidates. The studies are often performed in conjunction with mass balance excretion studies, using plasma, urine, or bile samples from mice, rats, dogs, monkeys, or humans. Metabolite identification studies can also be performed in vitro using liver microsomes, hepatocytes,
or other preparations from humans or animal species.
Drug Excretion
An excretion study can provide fundamental information about the rates and routes of elimination of a new drug candidate. Mass balance studies are often an important component of regulatory submissions. We perform various mass balance studies in mice, rats, and dogs. Typically, a radio-labeled drug is administered intravenously and/or orally, and excretion of radioactivity is monitored in urine, feces, and occasionally bile. In addition to providing information on the relative rates of excretion in urine and bile, these studies can indicate the percentage of an oral dose systemically absorbed. Further information can be obtained by analyzing mass balance study samples for parent drug and individual metabolites using LC/flow scintillation detection, UV detection or LC/MS/MS to find out
routes of elimination of parent compound and its metabolites.
Pharmacokinetics & Toxicokinetics
HD Biosciences has expertise in designing, performing, and interpreting the results of pharmacokinetic studies in all species. Study design and selection of the appropriate model to be used are often customized to meet the project needs. Surgical preparations can be performed, if required. For example, pharmacokinetic study samples might include blood, bile, or other matrices, as well as tissues or tumor specimens that have special bioanalytical requirements. Analysis of pharmacokinetic samples is typically performed using LC/MS/MS. We perform pharmacokinetic studies in mice, rats, dogs, and monkeys for projects at the discovery screening stage (rapid turnaround to meet high-through-put needs), IND-enabling studies, as well as toxicokinetic studies.The data are interpreted
our Pharmacokinetics staff using industry-standard WinNonlin software.
We provide the following services:
Non-compartmental pharmacokinetics
Compartmental pharmacokinetics/simulations
Ascending dose (assessment of dose proportionality)
Dose linearity after repeat doses
Drug interaction studies
Pharmacodynamic and PK/PD modeling
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HD Biosciences (China) Co.,Ltd
590 Ruiqing Road
Zhangjiang East Campus, Pudong, Shanghai 201201,
P.R.China
Tel: +86 (21) 5116 3700
Fax: +86 (21) 5116 3766
info@hdbiosciences.com
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