Pharmacokinetic (PK)
Obtaining Pharmacokinetic (PK) data is a key requirement in the evaluation of new chemical entities. A quantitative measure of drug exposure is always needed for the sound interpretation of preclinical efficacy studies. PK data is also necessary before toxicology studies can be performed. 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.
Delivery Methods
Bio-Quant'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)
High Throughput Cassette PK Screening
For high throughput PK screening of compounds, Bio-Quant offers cassette dosing of up to 5 compounds simultaneously assuming analytical methods allows differentiation. It should be noted that T1/2 is sometimes affected by the dose administered and by the number of points used for the non compartmental calculation. The expected correlation between single and cassette dosing is usually in the range of an r=0.602.
PK Analysis in Diseased and Tumor Bearing Animals
Animal Species Offered
Bio-Quant offers PK studies in the following animal species:
- Mice
Rats
Guinea Pigs
Hamsters
Ferrets
Pigs (domestic and minipigs)
Dogs
Cats
Gerbils
Rabbits
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. |
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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.
PK Studies in Large Animals
Bio-Quant maintains colonies of large animals (dogs and pigs) 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. |  |
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