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®
Tools

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.

With over 25 years of combined experience, PharmOptima and Ophthy-DS have teamed up to provide a comprehensive portfolio of ocular drug discovery, development, safety, and pharmacokinetic services. A team of industry-trained scientists and on-staff veterinary ophthalmologist ensure the efficient development and coordination of your unique preclinical ocular program, from target validation and assay development to identification and optimization of clinical candidates.

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

Ophthalmic Models

Ocular & Efficacy Models

Rabbit

  • DL-AAA (Dutch Belted and New Zealand Rabbits)
  • VEGF induced retinal vascular leakage (wet AMD)
  • Laser induced CNV
  • LPS induced Uveitis
  • NaIO3 Induced Retinal Degeneration
  • Glaucoma - Increased Ocular Pressure
  • Corneal Injury
  • Non-GLP Safety

Rat

  • Blue light damage (dry AMD)
  • Laser induced CNV
  • Glaucoma - Morrison’s Model
  • Ischemia Reperfusion
  • Allergic Conjunctivitis
  • Transgenic Models (P23H, S334TER, RCS…)
  • Dry Eye
  • NaIO3 Induced Retinal Degeneration
  • STZ Induced Diabetic Retinopathy
  • Non-GLP Safety

Mouse

  • ApoE AMD
  • Laser induced CNV
  • Non-GLP Safety

Other Studies Completed

  • formulation comparisons using topical delivery and analysis of anterior and posterior chamber ocular fluids & tissues
  • prodrug ocular pharmacokinetics
  • test article efficacy versus VEGF induced retinal leakage
  • bioanalytical assays established for batches of compounds sent monthly for screenings
  • hundreds of ocular compounds screened

Bioanalytical

Our bioanalytical services goal is meeting your project schedules and providing the highest quality data to facilitate decisions concerning your drug candidate. Our staff is skilled in method development and validation for analysis of drugs and metabolites in biological matrices including peptides and other challenging compounds by leveraging three different LC/MS platforms (SCIEX 6600, SCIEX 4000, Thermo TSQ Quantum Ultra). Analyses can be conducted following GLP guidelines, as needed.

What we can do for you:

  • rapid screening bioanalytical methods
  • bioanalytical method development and validation per FDA Crystal City and OECD guidance
  • preclinical pharmacokinetics
  • PK/PD assessment
  • toxicokinetic investigations of absorption and clearance
  • bioavailability/bioequivalence
  • ocular PK
  • prodrug and metabolite PK

Biochemistry

PharmOptima staff has provided biochemistry services to companies world-wide. We have cloned and expressed proteins as well as customized 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 and traditional methods
  • antibody purification and labeling (eg HRP and sulfo-tag ruthenium for ECL applications)
  • stable mammalian cell line generation and characterization
  • protein expression
    • prokaryotic expression systems (E.coli)
    • eukaryotic expression systems (mammalian cell and insect cell/baculovirus)

We develop
biomarkers
  • biomarkers
  • assays

We have the expertise and experience to clone and express proteins if what you need is not commercially available. Utilizing MSD Technology*, biomarkers are available from human, rat, mouse and non-human primate in many cases.

  • 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-Life Capabilities

Your compounds can be tested in PharmOptima’s 7,000 square foot vivarium for in vivo bioavailability, metabolism, pharmacologic efficacy, and tolerance.

What we can do for you:

  • extensive ophthalmic and surgical expertise
  • transgenic mouse colony capabilities
  • KKAy diabetic mouse studies
  • evaluation of drug tolerance, integration of studies with drug delivery and pharmacokinetics (PK)

Routes of Administration

  • Oral Gavage
  • Subcutaneous
  • Intravenous/Infusion
  • Intraperitoneal
  • Intramuscular
  • Intravitreal
  • Topical (Ocular)
  • Dermal
  • Intratracheal
  • Intranasal Inhalation/Instillation
  • Intracerebroventricular
  • Intrathecal
  • Stereotaxic ICV Infusion

Surgical Capabilities

  • Kidney injury (ischemia-reperfusion)
  • Partial nephrectomy for evaluating hemostasis
  • Wound healing (excisional/incisional
  • Bone fracture and repair BMD compound efficacy
  • Chronic and acute cardiac ischemia
  • Intact spinal cord collection

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)