In Vivo ADME Studies
Absorption, Distribution, Metabolism and Excretion (ADME) studies are a vital part of the
comprehensive safety evaluation of a new chemical entity. MDS offers ADME studies in small
animals, using radio-labeled materials, that you provide or MDS synthesizes for you. Routes of
administration include oral, intravenous, dermal, intraperitoneal, inhalation, intrathecal, and
infusion as well as other intended delivery methods for your compound. These in-life studies
provide information for:
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Metabolite isolation and characterization
Bioavailability evaluations
Bioequivalence studies
Formulation screening and optimization
Dosing frequency
Formulation
Routes of administration
Exposure
Interspecies comparisons
Pharmacokinetics/ADME Studies
MDS-T-101 Material Balance or Accountability Study
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Groups of 5 male and 5 female rats at a single dose level
Daily collection of urine and feces for 7 days
Collect blood and major internal organs, and retain carcass upon necropsy
Total radioactivity level in each sample is assayed and the recovered dose is compared
with the administered dose. The percentage of distribution of the administered dose in
urine, feces, and each major internal organ and the half-time for excretion are
calculated.
MDS-T-101-R Optional Studies
 Analysis of CO2 in expired air
 Analysis of injection site (e.g., if the dosing route is percutaneous or intramuscular)
 Two dose levels instead of one
 Species other than rats (e.g., rabbits)
 Repeated-dose study (unlabeled compound is administered daily for 13 days; on the 14th
day a radioactive dose is administered)
 Major metabolites - isolation, characterization
MDS-T-102 Plasma Level and Bio-availability Study
The objective of this study is to examine the pharmacokinetic profiles of the chemicals under
test. These studies can be conducted by using unlabeled chemicals provided that appropriate
analytical procedures (e.g., HPLC) are available.
 Groups of 5 male and 5 female rats per route of dosing
 One group is dosed intravenously and the second group is dosed by an extra-vascular
route (e.g., oral, percutaneous)
 The dosages for the 2 groups need not be identical
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Blood is sampled at frequent intervals (e.g., 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, and 48 hr),
and plasma levels of the chemical are assayed.
The plasma- concentration-time data are analyzed to obtain the pharmacokinetic profile,
including the area under the curve (AUC). Comparison of the AUCs after extra-vascular
and intravenous dosing, after correcting for the dosage, provides a measure of
bioavailability. Alternatively, if a radioactive chemical is used, comparison of the
administered doses excreted in urine can be used to calculate the approximate
bioavailability of the orally dosed chemical.
MDS-T-102-R Optional Studies
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Species other than rats
Plasma protein-binding study
MDS-T-102 Pharmacokinetics Studies of Nucleotide Therapeutics
We can conduct tissue distribution studies of nucleotide-based materials using quantitative
polymerase chain reaction (PCR), capillary electrophoresis, or in situ hybridization methods.
Studies are designed to fit the needs of each particular test article.
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