Pharmacokinetic (PK), ADME and Efficacy Studies

Our scientists perform PK, bioavailability, bio-distribution and bio-equivalence studies for new or experimental drugs. Our staff has investigated a wide variety of small molecule drugs and protein biopharmaceuticals. Standard drug efficacy testing can be performed in a variety of animal models using protocols supplied by you, or developed by us.

PK Studies

In a typical PK study, blood samples are obtained from test animals following a single dose or a timed perfusion. Plasma samples are separated and analyzed. Typically, if the drug is going to be administered orally, both an i.v. PK and an oral PK should be run. From these two studies both the bio-availability and the pharmacokinetics of the drug can be calculated. The data is also used to generate concentration vs. time curves and allow the determination of fundamental PK parameters such as Cmax, Tmax, AUC, drug clearance, terminal elimination half-life, oral bioavailability and volume of distribution.

Time Points

The time points (and hence the number of animals) depend on the compound, the route of administration, and its half-life. For a small molecule administered i.v., we would recommend 5 minutes, 15 minutes, then 1, 2, 4, 6, and 24 hr because the half-life is short and because it is given IV. On the other hand, for a monoclonal antibody that has a half-life of 10 days, there is no reason to do a number of time points on Day 1. In this case, we would look at 4 hr, 24 hr, and then days 2, 4, 7, 10, 14, 17, 21, and 28.

Data from a small molecule administered orally to Sprague Dawley rats is shown below:

Delivery Methods

Perry Scientific’s scientists are experienced with all standard delivery methods including:

• Oral (using capsules, tablets or oral gavage)
• Arterial
• Intravenous
• Continuous infusion using mechanical or osmotic pumps
• Intramuscular
• Intraperitoneal
• Subcutaneous
• Nasal Mucosa, Nasal Cavity or Tracheal
• Bronchial (Inhaled Aerosols)

Animal Selection

Perry Scientific offers PK studies on all species of animals. Our lowest cost studies are most commonly performed on rats or mice, but we also offer PK studies on large animals.

PK Studies in Mice

A mouse PK study is a normally a terminal study in which sample collections are made by cardiac puncture (unless the assay allows for micro sample size where the mice can be bled more than once). For a mouse PK, we typically use 3-5 mice/sex for each time point.

PK Studies in Rats

Rats can be bled up to seven times in a day in a PK study. To obtain more time points the groups can be divided accordingly. For example, 3-5 rats/subgroup and perhaps 2 subgroups per dose, (subgroup A bled at 0.5, 2 and 6 hr post dose and subgroup B bled at 1, 4, and 12 hr post dose). If the time points are very close together, we can pre-cannulate the rats to facilitate these bleeds. Because of the multiple bleeds, the number of rats will be about a seventh of that required for mice

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PK Studies in Large Animals

Perry Scientific maintains colonies of large animals for PK studies. Many companies house large animals at our facility especially for their PK studies. This is a special service we offer, and in this case these animals are reserved for a customer’s exclusive use. With larger animals, multiple bleeds can be made in a single day. Note that only 15% of the blood volume of the animal can be bled per day in a survival study.