Medicilon offers a complete range of drug metabolism services, with the capability to design studies specifically tailored to your requirements. Our expertise in supporting your lead selection, along with the benefits from our on-site vivarium, provide comprehensive support for your preclinical discovery research programs.
-- The distribution-related aspects are plasma protein binding, on the one hand, and brain tissue, microsomal proteins, protein binding in FBS, and whole blood plasma distribution ratios, on the other hand.
-- In terms of permeability and transport, the main focus is on the Caco-2 model and various transporters, including P-GP and BCRP, which are the main efflux transporters.
-- Some UNTAKEs are getting more and more attention nowadays, which are the uptake transporters, and in the in vitro drug-drug interaction DDI studies, which are mainly P450 enzyme inhibition.
-- Then there are time-dependent inhibition, P450 induction, and metabolic enzyme phenotype, metabolite identification studies.
-- There are more types of in vivo DMPK, and we can choose different sizes of animal species, different routes of drug delivery, blood collection strategies, etc. on the needs.
-- In addition to plasma PK, for Central Nervous System (CNS) drugs, we need to conduct in vivo studies of blood-brain barrier permeability (BBB), collect brain tissue and CSF, and determine the drug concentration in brain tissue and CSF. It is also combined with protein binding assays to evaluate the obstruction of drug transport by the blood-brain barrier and to more accurately guide the development of CNS drugs.
-- Other tests such as tissue distribution, excretion tests, and drug interaction DDI are also available to place at an early or later stage on the need.
In vitro Drug Metabolism Studies
Identification of Metabolite Structures
Generation and Isolation of Pure Metabolites
Quantification of Metabolites Drug Metabolites in Animal Toxicokinetic Studies
Quantification of Drug Metabolites in Clinical Trials and Pharmacokinetics
Clinical Drug-Drug Interaction Studies
Pediatric Drug Metabolism
Metabolic Stability Using Liver Microsomes or Cryopreserved Hepatocytes
Metabolite Identification and Characterization
Species Comparisons of Metabolite Profiles
CYP and UGT Reaction Phenotyping
Stability in Blood and/or Plasma
Stability in Gastric and Intestinal Fluids
Glutathione Conjugate/Reactive Metabolite Detection
By providing critical information early in the drug development process, our ADMET screening assays help you to identify and focus efforts on compounds that have the greatest, likelihood of success. Once a lead candidate is selected, both qualitative and quantitative analyses of radiolabeled and nonradiolabeled compounds are provided in a range of in vitro test systems. Studies are designed to complement the metabolism, TK and bioanalytical investigations undertaken in pharmaceutical product development. Other laboratory assays that balance our in vitro metabolism services include cell proliferation, cytotoxicity, herg blockade and protein binding.
Metabolism plays an essential role in the elimination of drugs and other foreign ingested chemicals (xenobiotics) from the body. In some cases, especially during oxidative metabolism, numerous chemical procarcinogens form reactive metabolites capable of covalent binding to biopolymers such as proteins and nucleic acids leading to mutagenic, teratogenic, cytotoxic and carcinogenic effects.
Drug biotransformation could be classified into two phases:
Phase I (Functionalization)
Non polar drugs are either inactivated; or activated in some cases, by metabolic introduction of polar functional group into the substrate molecule through:
(a) Oxidation: hydroxylation, oxide formation, alcohol oxidation, aldehyde oxidation, deamination, dealkylation, desulfuration and dehalogenation.
(b) Reduction: azo reduction, nitro reduction and aldehyde or ketone reduction.
(c) Hydrolysis of amides and esters.
(d) Removal of non-polar alkyl group to expose potential polar group.
Phase II (Conjugation and Enzymatic Synthesis)
In this phase an existing functional group (already presents in the drug molecule or created by phase I metabolism) such as alcohol, phenol, amine is masked or inactivated by a process of:
(a) Synthesis, such as methylation, acylation, thiocyanate formation and mercaptouric acid formation.
(b) Conjugation with glucuronic acid, amino acids or sulfate which further increase the polarity of the drugs or (xenobiotics).
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