Solutions

There is an immense requirement for efficacy and safety assessment during drug discovery. Prior to actual dosing in animals, several reliable and cost-effective in vitro assays can serve as surrogates and indicators of the ADME fate of compounds in vivo. We provide a comprehensive and flexible range of in vitro DMPK/ADME studies designed to cover the majority of activities in the hit-to-lead and lead optimization phase through to candidate selection. We also offer in vitro metabolite profiling, structural elucidation, and DDI (drug-drug interaction) studies during pre-clinical development and clinical-stage projects.

Stellixir Biotech has multiple formats for In vitro assays. We have a flexible ADME screening approach that suits different drug discovery and development pipeline stages. It enables characterizations of chemical series that often help determine the metabolism and drug interactions while profiling a compound candidate. The assays are chosen to make the best match of throughput, data resolution, and quality requirements specific to your project targets. Stellixir Biotech has state-of-art facilities combined with a researcher network across the globe. Our goal is to support a continuum for compound design contributing to lead candidate selection. We are positioned to design an optimal DMPK ADME program that will work and support your drug discovery and development needs.

At Stellixir Biotech, we care to understand your needs. We enable quick attention to your requirement with our customer care.

Services Offered:

Physico-Chemical Assays:

We provide compound profiling for improved physicochemical characteristics. We perform solubility assessment, plasma protein binding, permeability, absorption, stability, and reactivity of a drug. We are committed to providing the best analysis services with a team of experts at Stellixir Biotech.

Assays Include:

Log D (distribution co-efficient), Log P (partition coefficient), Kinetic solubility, Thermodynamic solubility, pH-dependent solubility, Solubility in bio-relevant medium, Chemical stability, Stability in bio-relevant medium, Plasma stability, Whole blood stability, Chemical reactivity.

In Vitro Metabolism:

We assess the efficacy and safety of drugs through metabolic assays. Here we support calculating drug efficacy, dosage rate, and safety profile. We use liver microsomes, S9 fractions, and hepatocytes, to get precise and accurate data on in vivo clearance mechanisms.

Assays Include:

CYP & UGT reaction phenotyping, microsomal stability, S9 stability, hepatocyte stability, hepatic uptake, plasma stability, metabolite profiling and identification, microsomal binding.

Drug-Drug Interactions:

Study of inhibition and induction of the drug-metabolizing enzymes are the most common types of metabolic drug-drug interactions. Concomitant administration of two or more drugs can cause increased or decreased drug exposures. Inhibition or induction of CYP450 significantly alters the plasma level of administered drug thereby affecting its toxicity or efficacy. We provide a range of services to investigate drug-drug interactions including cytochrome P450 inhibition. We also provide a cytochrome P450 and UGT reaction phenotyping service using a recombinant enzyme.

Assays Include:

Cytochrome P450 and UGT reaction phenotyping, cytochrome P450 induction, cytochrome P450 inhibition, cytochrome P450 relative induction score, cytochrome P450 Ki, PXR, and AhR nuclear receptor activation, time-dependent inhibition (IC50 shift), reaction phenotyping (CYP Identification), UGT inhibition.

Protein Binding:

We perform plasma protein binding assays to assess drug distribution and an unbound fraction of drugs in proteins. These fractional unbound values when used with pharmacokinetic and pharmacodynamic modelling, help our clients better predict drug-drug interactions.

Samples we study with:

Plasma, Tissue homogenate, Blood, Furin microsomes, Furin (hepatocytes).

Permeability and Transporters:

Our comprehensive range of assays measure oral absorption properties of the drug, permeability, transport across cell membranes, and bioavailability. If you are looking to measure ADME properties of drugs you can reach out to us at Stellixir Biotech as we customize your requirements and provide the best results.

Assays Include:

GIT-PAMPA, BBB-PAMPA, Intrinsic permeability in Caco-2 cell models, Breast cancer resistance protein (BCRP)-MDCK-II, and Multidrug resistance protein (MDR1)-MDCK-II, Lilly laboratories cell-porcine kidney (LLC-PK1)-MDR1.

Cytochrome P450 Induction:

Efficient cytochrome P450 (CYP) induction assays evaluate the metabolism of test compounds and estimate the potential clearance pathways through CYP reaction phenotyping methods.

Assays Include:

HepG2 cell line (CYP3A4)-reporter gene-based assay, Human primary hepatocytes-based assays.

Metabolite Identification and Biotransformation:

We identify various metabolites and analyse their impact on drug candidates to assess drug safety. We perform complete structural data analysis of metabolites using high-end instrumentation.

Assays Include:

Intrinsic clearance (CLint) and high-level profiling of the top three metabolites in liver microsomes and hepatocytes, Metabolite soft spot analysis, Metabolite fingerprinting, and High-throughput reactive metabolite screening.

Key Instrument:

liquid chromatography (LC) coupled with high-resolution mass spectrometry (HRMS) and mass spectrometry (MS).

In Vivo Pharmacokinetics:

We offer in vivo pharmacokinetics (PK) services to study ADME of drugs and help our clients in the discovery, selection, efficacy, and development of drugs. We assess plasma exposure, bioavailability, and dosing frequency of the drug or test compound to understand its efficacy. Drug administration routes include intravenous bolus, intravenous infusion, oral, intramuscular, intraperitoneal, intraocular, intraduodenal, subcutaneous, topical, and inhalation using mice, rats, and rabbits as animal models. We provide excellent turnaround time and affordable pricing for our PK/PD services.

Assays Include:

Bioequivalence PK studies in rodents, cassette dosing pharmacokinetics, mass balance pharmacokinetics, tissue distribution studies, dose proportionality pharmacokinetics, mechanistic PK models, in vivo drug-drug interaction (DDI) studies in rodents, serial blood sampling in mice, intravenous infusion in jugular vein cannulated mice and rats, crossover pharmacokinetics in dual vein cannulated rats.

Pre-Formulation Services:

We provide facilities to quickly prepare formulations for single-dose intravenous pharmacokinetic studies. Drug formulations are provided in various forms such as solutions, suspensions, creams, emulsions, ointments, and gels.

Bioanalysis Quantitation:

We provide advanced bioanalytical method development and qualification including automated sample handling. Our expertise lies in handling sensitive small molecules, light-sensitive and cytotoxic compounds. We conduct bioanalysis in multiple bio-matrices to support tissue distribution studies.

Assays Include:

Dried blood spot analysis, bioanalysis of chiral compounds, pharmacodynamic (PD) biomarker testing, and biomarker modulations in complex pre-clinical and clinical biological matrices such as plasma, serum, urine, tissue homogenates, and cerebral spinal fluids.

PK/PD Modelling and Simulations:

Pharmacokinetic/ pharmacodynamic (PK/PD) modelling and simulation help in selecting the appropriate dosage levels for efficacy studies. Our models provide an accurate and precise prediction of pharmacokinetic parameters.

Assays Include:

PK/PD/ efficacy correlations based on exposure or Cmax, PK modelling and simulations, Scaling of preclinical PK to predict human PK using an allometry approach, Prediction of first-in-human (FIH) and median efficacious doses (MED), Pharmacokinetic parameter evaluations using Phoenix WinNonlin.

Large Molecule Analysis:

We analyse large molecules using mass spectrometers. The assays include top-down intact analysis or bottom-up tryptic digestion approaches to analyse large molecules such as peptides, oligonucleotides, and monoclonal antibodies.

Looking for customized in vitro ADME/DMPK services, you can contact us, at info@stellixir.com and we will be there to help you to meet your requirements.