DMPK/ADME
We are experienced at conducting in vivo pharmacokinetic and metabolism studies. Our in vivo proof of concept testing and model development is designed to confirm drug delivery, efficacy, and tolerance in rodents and rabbits.
What we can do for you:
- pharmacokinetic analysis of blood (plasma)
- metabolite isolation and characterization
- bioequivalence studies
- formulation screening and optimization
- bioavailability studies (po, sc, im, ip, intratracheal)
- single dose and multiple dose PK studies
- discovery liquid formulation development and optimization
- drug distribution in tissue/organ and body fluid and determination of blood and brain ratio for brain penetration
- metabolic kinetics with active metabolites
- PK study for design of dose and dose regimen in various rodent disease models
- PK analysis using WinNonlin®
Ocular PD/Efficacy
Our ophthalmic services begin, run and conclude with a high level of technical expertise.
From specialized ocular dosing by trained scientists, to the precise dissection of specific ocular tissues by our specialists, followed by exacting sample processing and bioanalysis by PharmOptima’s experienced staff; we stand out against the large CRO model of generalized necropsy technicians and crash & shoot discovery bioanalysis. Our bioanalytical team has extensive experience processing, homogenizing and extracting ocular fluids and tissues. We have developed LC-MS/MS methods for hundreds of compounds.
What we can do for you:
- validate bioanalytical methods following current FDA Crystal City and OECD guidances
- perform cross validations for additional species and matrices
- assay plasma and dosing solutions from regulated animal safety studies (i.e. GLP) and clinical trials
- assay metabolism of drugs/prodrugs in ocular tissue
Bioanalytical
Our bioanalytical services goal is to meet your project schedules and providing the highest quality data to facilitate decisions concerning your drug candidate. Our scientists are skilled in method development, validation, and sample analysis of small and large molecular weight compounds, metabolites, and peptides in biological matrices using liquid chromatography with tandem mass spectrometry (LC-MS/MS). We have three different LC/MS platforms (SCIEX 5000, SCIEX 4000, Thermo TSQ Quantum Ultra). Analyses can be conducted following FDA GLP guidelines, as needed.
What we can do for you:
- rapid screening bioanalytical methods
- method development, validation, and sample analysis following FDA GLP and OECD guidances
- preclinical pharmacokinetics
- PK/PD assessment
- toxicokinetics
- bioavailability/bioequivalence
- Ocular, prodrug and metabolite PK
Biochemistry
PharmOptima staff has provided biochemistry services to companies world-wide. We specialize in developing custom assays to meet specific client research needs.
What we can do for you:
- cell-based assays
- biomarker assays
- ELISA
- MSD electrochemiluminescence
- ligand binding assays
- Protein purification and characterization:
- Affinity protein purification methods limited to:
- His-tag
- GST-tag
- MYC-tag
- FLAG-tag
- Fc fusion proteins
- Antibodies via protein A/G
- Traditional methods
- Affinity protein purification methods limited to:
- antibody purification and labeling (eg Biotin and sulfo-tag ruthenium for ECL applications)
- stable mammalian cell line generation and characterization
- protein expression
- eukaryotic expression systems (mammalian cell and insect cell/baculovirus)
We develop biomarkers and assays.
Utilizing MSD and ELISA Technology*, biomarkers are available from human, rat, mouse and non-human primate in many cases. A few examples include:
- metabolic markers
- oncology markers
- vascular markers
- cytokines and chemokines
- cell signaling pathways
- Alzheimer’s (Aβ38, Aβ40, Aβ42 and Tau, Total Tau)
- kidney injury
- cardiac and muscle
- liver injury
- inflammation
We provide custom assay development services to customers worldwide. PharmOptima’s scientists can work with you to develop assays to meet your specific research needs. Our scientists have extensive experience in the different custom assay development services listed below.
- Immunosorbant assays, traditional ELISA and ECL
- Development of multiplex immunoassays using MesoScale Discovery technology
- Cell-based assays: signal transduction (eg cAMP)
- Ligand binding assays
- Enzyme assays and kinetics
- Inhibitor mechanism and validation
- MSD Certification such as Human Aß42 and Human Total Tau
In vivo
Your compounds can be tested in PharmOptima’s vivarium for in vivo bioavailability, metabolism, pharmacologic efficacy, and tolerance.
What we can do for you:
- extensive ophthalmic expertise
- transgenic mouse colony capabilities
- evaluation of drug tolerance, integration of studies with drug delivery and pharmacokinetics (PK)
Routes of Administration
- Oral Gavage
- Subcutaneous
- Intravenous/Infusion
- Intact Spinal Cord Collection
- Intraperitoneal
- Intramuscular
- Intravitreal
- Topical (Ocular)
- Dermal
- Intratracheal
- Intranasal Inhalation/Instillation
- Intrathecal
Ocular Tissue Collection
Anterior
- Aqueous humor, Cornea, Conjunctiva (palpebral and/or bulbar)
- Meibomian Glands
- Trabecular meshwork, Iris-Ciliary body, Lens
Posterior
- Vitreous humor, Optic Nerve
- Sclera, Choroid (central and/or peripheral)
- Retina (central and/or peripheral)
Ocular Tissue Collection
Anterior
- Aqueous humor, Cornea, Conjunctiva (palpebral and/or bulbar)
- Meibomian Glands
- Trabecular meshwork, Iris-Ciliary body, Lens
Posterior
- Vitreous humor, Optic Nerve
- Sclera, Choroid (central and/or peripheral)
- Retina (central and/or peripheral)
SMN Assay Development
Our Spinal Muscular Atrophy (SMA) services begin with research and concludes with a high level of technical expertise.
GD3 researchers have worked with organizations such as the Spinal Muscular Atrophy Foundation, universities and pharmaceutical companies on critical SMA research. SMA, the leading genetic cause of infant death, is caused by defects in the Survival Motor Neuron 1 (SMN1) gene that encodes SMN protein. SMA patients have at least one copy of a similar gene (SMN2) that produces SMN protein, although in reduced amounts. Infantile-onset spinal muscular atrophy is the most common genetic cause of infant mortality, typically resulting in death preceding age two. Low-level production of survival motor neuron protein (SMN) results in a loss of specialized nerve cells called motor neurons that control muscle movement.
In recent years, new SMN-enhancing therapeutics have been developed. Since limited knowledge of baseline and drug-induced SMN levels in disease-relevant tissues hinders efforts to optimize these treatments, clinical trials in this population require understanding disease progression and identifying meaningful biomarkers to hasten therapeutic development and predict outcomes. Clinical studies require a readily accessible means of tracking SMN levels in the patient. GD3 scientists have developed an immunoassay system that monitors SMN protein levels in whole blood. The assay can detect and quantify SMN protein from as little as 5 microliters of whole blood, which can be obtained from a finger prick.
GD3 experts have supported research in published studies of spinal muscular atrophy, including:
- Whole blood survival motor neuron protein levels correlate with severity of denervation in spinal muscular atrophy
- Natural history of infantile-onset spinal muscular atrophy
- Age-dependent SMN expression in disease-relevant tissue and implications for SMA treatment
- Mild SMN missense alleles are only functional in the presence of SMN2 in mammals
- Evaluation of potential effects of Plastin 3 overexpression and low-dose SMN-antisense oligonucleotides on putative biomarkers in spinal muscular atrophy mice (plastin 3, also known as T-plastin or fimbrin)
- Normalization of Patient-Identified Plasma Biomarkers in SMN2 Mice following Postnatal SMN Restoration
What we can do for you:
- Novel Method Development and Standard use:
- Immuno Assays
- Immunogenicity Assays
- Cell-based Assays
- Nuclease Protection Assays
- Ligand Binding Assays
- Oligonucleotide Assays
- ELISA Assays
- SMA transgenic mouse colony capabilities
- LC-Mass Spec analysis of small molecules
Let GD3 collaborative biology/bioanalytical teams generate high-quality leads to advance your programs.
