Drug Metabolism and Pharmacokinetics (DMPK)
Why select Frontage for your DMPK work?
The Frontage DMPK group is similar in function and capabilities as those found in large pharmaceutical companies, providing in vitro and in vivo drug metabolism and pharmacokinetics support for discovery and development projects. Here is an overview of our services:
Discovery Drug Candidates
- Metabolic stability in liver microsomes, or in cryopreserved or freshly cultured hepatocytes
- In-vitro metabolite profiles of drug candidates to identify metabolic soft spots or potential reactive sites
- Reactive metabolite formation evaluations using trapping assays (e.g. GSH, CN)
- Comparisons of in-vitro and in-vivo metabolite profiles across species utilizing LC/MS/UV
- Metabolite identification and characterization by LC/MS and NMR
- In-vitro cytochrome P450 inhibition studies (based on LC/MS/MS assays)
- CYP reaction phenotyping studies
- In-vitro plasma protein binding
- Discovery PK studies, including formulation development and preparation, dosing, sample collections, and quantitative analysis of analyte and metabolites in plasma, tissues and other biological matrices. Studies conducted in rodents, canines and non-human primates
- Blood partitioning studies
Development Drug Candidates
- Comprehensive metabolite profiling and identification in multiple species, toxicology species selection, and determining potential metabolic liabilities
- Metabolite profiling in plasma samples from PK or early tox studies (single-dosed vs. multiple dosed animals)
- Reaction phenotyping, verifying the major enzymes involved in metabolism of a compound
- Cytochrome P450 inhibition studies. Definitive IC50 and Ki determinations
- Cytochrome P450 induction in livers of rodents, canines and non-human primates (ex-vivo studies)
- In vitro intrinsic clearance of compounds using microsomes or hepatocytes
- Enzyme kinetic studies for metabolite formations, especially to obtain Km and Vmax values
- Mechanistic or routine metabolism studies with stable isotope labeled (13C, 2H) or radiolabeled (14C, 3H) compounds. In-house capabilities to synthesize stable isotope labeled compounds for metabolism studies
- Delineation of metabolic pathways to understand metabolism of NCEs in various species using non-labeled or radio-/stable-isotope labeled analogues
- Excretion and mass balance studies in rodents, dogs and NHP using radio labeled compounds
- Biliary excretion studies (non-radiolabeled or radiolabeled)
- Qualitative analysis of First In Human plasma and urine samples from SAD / MAD studies
- For the purposes of showing coverage of human-specific metabolites in tox species, Frontage can quantify metabolites in plasma from humans and preclinical species previously conducted using published strategies. We are specialists in developing cost-effective MIST strategies for clients using non-radiolabeled compounds
Our strengths include:
- Personnel from pharmaceutical industry – strong background/experience in DMPK, technical skills as well as understanding of clients’ expectations.
- The ability to provide good scientific input to study designs and interpretation of data to influence decision making process (e.g. value-added experiments)
- Continual interaction at a personal level through routine TC with clients.
- The ability to take on difficult studies/challenges, problem-solving
Compared to large CROs, the Frontage DMPK group offers the attention of a small organization, scientific exchanges, and the flexibility to change study designs, priorities, etc. at the client’s request. Yet the group also has the ability to leverage resources across the Frontage organization, including a:
- huge bioanalytical capacity/capability
- strong formulation group (to solve any potential formulation issues)
- excellent QA group (several FDA, client audits)
- strategic build-up of drug metabolism and pharmacokinetic capabilities in USA/China
Frontage provides cost-effective and efficient ways to conduct DMPK studies through automation and the hiring/retention of the best scientists in the industry.
The DMPK group is to be regarded as an extension of your existing capabilities. We are: Complimentary, supplementary and interactive.
Download the Frontage DMPK Services brochure.