I need to carry out pharmacokinetics study on rats by HPLC. Should I take drug from tissue samples for this purpose or only blood samples investigation will be enough?
Biodistribution is different from actual pharmacokinetics. From blood samples you can study Cmax, AUC, t1/2 and so on but if you have, for example, a nanoparticle, it may accumulate your drug in specific organs or lession zone so I guess you can collect some organs to test this. Study papers publicated about that and also take into account the administration route and the physical state of your drug (soluble, nanoparticulated or aggregated in some sort of dispersion). Good luck.
Dear Friend,
With HPLC you can determine the concentration of a drug (compound) in the blood. On the other hand, for the determination in tissues you need biodistribution imaging after dissection.
For example, a new compound would be injected intravenously into a group of 16-20 rodents (typically mice or rats). At intervals of 1, 2, 4, and 24 hours, smaller groups (4-5) of the animals are euthanized, then dissected. The organs of interest (usually: blood, liver, spleen, kidney, muscle, fat, adrenals, pancreas, brain, bone, stomach, small intestine, and upper and lower large intestine, etc.) are placed in pre-weighed containers, then into a device that measures gamma radiation. The results give a dynamic view of how the compound moves through the animal.
Raty JK, Liimatainen T, Wirth T, et al. (October 2006). "Magnetic resonance imaging of viral particle biodistribution in vivo". Gene Therapy. 13 (20): 1440–46.
Hoping this will be helpful,
Rafik
You can extract the drug from the organs and then make quantification by HPLC.
Thank you all for answers!
David, we investigate nanoparticles. Are there protocols/guides on its PK study ? Are ADME and PK study the same things?
I'm not sure. We haven't done a PK study yet although we are planning to do a preliminar study of drug quantities in blood and some organs after nano particle subcutaneous administration. ADME refers to absorption, distribution, metabolism and elimination. Parmacokinetics studies those process but the actual mathematical analysis is done by what I said before (Cmax, AUC, T1/2, and others).
you have to determine the concentration in blood and in different tissues. there are many methods to do that.
Dear all,
The PK studies are indeed:
1)the animal short-long term studies and
2)early phase human studies were PK is primary or even secondary objective (as in FIH) and is based on plasma and urine common PK parameters estiumation.
Biodistribution is one of the PK steps which is measured in PK studies by a preliminary parameter Vd/Vss/Vz=volume of distribution. In case during animal or human studies there is a high Vd, it should be explained. this high distribution should already be investigated in animals (different organs macro-microscopic analysis and samples bio-analysis), to have an idea about the distribution profile. More appropriate will be to perform animal ADME with C14. If not done, then in human high distribution should be explained by ADME or M&S (if the whole PK/PD pathway is known).
Simple PK assessments in human early phase studies may be not enaouf to clarify high distribution of drugs.
Narine, thanks a lot!
Could you recommend some literature on volume of distribution determination?
initially you can study the pk only from blood values and you can calculate apparent volume of distribution manually or by one of the pk software.
then you can study the biodistribution of the drug in different tissues in separate study
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