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Drug Metabolism and Pharmacokinetics (DMPK)
In vivo PK and TK
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. PK studies typically involve the use of fully conscious animals that have been appropriately catheterized for drug administration and sample collection. Special surgical preparations such as catheterizations of portal vein and bile duct, can also be performed, if required. 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.
HD Biosciences performs pharmacokinetic studies (all routes of administration including IP, IV, PO, SC etc.) in multiple species (rodent, dog, rabbit, guinea pig, monkey) 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 by our
Pharmacokinetics staff using industry-standard WinNonlin software.
Services include:
All routes of administration in multiple species
IP, IV, IM, PO, SC, etc
Rodent, dog, rabbit, guinea pig, monkey
PK parameters
PO: AUC0-last, AUCinfinity, Cmax, Tmax, T1/2, MAT, MRTinfinity
IV: AUC0-last, AUCinfinity, Cmax,T1/2, CL, Vss, MAT, MRTinfinity
In vivo PK profiling
dose proportionality
single dose vs. repeat dose
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, usually using equilibrium dialysis or ultrafiltration. Analysis of protein binding
samples is typically performed using LC/MS/MS methods.
Plasma Stability
In vitro plasma stability provides valuable information prior to in vivo PK testing. The samples containing test articles are incubated at 37 oC for different time. Analysis of
plasma stability samples is performed using LC/MS/MS methods.
Caco-2 cell permeability
Caco-2 cell permeability provides the data to predict absorption of drug candidates across the intestinal epithelial cell barrier. The drug absorption rates (Papp), recovery and its
potential as a P-glycoprotein substrate or inhibitor are assessed.
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 methods.
In Vitro Metabolism
We provide a full range of in vitro and ex vivo assays utilizing microsomes, S9 fractions, or 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 HD Biosciences has developed. 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.
Services include:
In vitro metabolism
Metabolic stability and half-life determination
CYP450 isozyme inhibition
CYP450 isozyme phenotyping
Time-dependent inhibition
Reactive-intermediate trapping
Metabolite identification
Utilizing the strengths of bioanalysis, LC/MS/MS, and NMR for metabolite identification studies are routinely performed.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.
Mass Balance
An excretion mass balance 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 radiolabeled 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 or LC/MS/MS to find out routes of elimination of parent compound and its metabolites. We also work with our partners for chemical synthesis if authentic samples of metabolites are required to
complete such projects.
In addition to the state-of-the-art analytical LC/MS/MS (with Q trap) facilities, HDB has the highly experienced analytical team led by the US major pharmaceutical company returnees with the track record of success in drug discovery, preclinical and clinical development. We have highly efficient team with fast turn around time. Our bioanalytical services involve the determination of drug concentrations in biological specimens derived from preclinical
to clinical trials. The techniques employed include LC/MS/MS and ELISA assays.
All assays follow SOPs in which both QC/QA and GLP-compliance are implemented. Our dedicated staff with strong scientific and regulatory knowledge will ensure to provide high
quality of services for our clients.
Services include:
LC/MS/MS method development
MS/MS method development
LC/MS/MS method validation according to USA standards
Specimen analysis for preclinical and phase I through IV clinical trials
Analysis of common sample matrices including plasma, serum, urine, CSF, bile, tissues
Animal efficacy, PK, TK, dose ranging Tox, in vitro metabolism, in vitro efficacy models, protein binding
Metabolite identification and screening
Drug profiles vs. administration route
Free drug vs. total drug level (protein binding)
Validation reports
Techniques include:
GLP-compliant LC/MS/MS analysis
GLP-compliant ELISA analysis
Solubility and Stability
Solubility of test article is determined in various single and mixed organic solvents and aqueous buffer at different pH. Stability in the solution is tested at different temperatures and in different storage periods. Concentration of test article in the solution is measured
using a either validated or scientifically validated HPLC method.
Formulation test
Absolute and relative bioavailability of test article is determined in mice, rats, dogs, and monkeys follow dose administration via various routes. Effect of stomach pH on oral
absorption is determined in either dogs or monkeys.
SPF Animal Barrier Facility
The 6000 f2 animal facility at HDB is specific pathogen free (SPF) and AAALAC-compliant facility. It contains 8 procedure rooms and 8 animal rooms which can house up to 2500 small animals. All the animal used for clients studies are provided by the certified animal supplier. All the study protocols and animal use are approved by the IACUC including a
veterinarian on site.
HD Biosciences (China) Co.,Ltd
590 Ruiqing Road
Zhangjiang East Campus, Pudong, Shanghai 201201,
Tel: +86 (21) 5116 3700
Fax: +86 (21) 5116 3766