Intraperitoneal injection (IP injection) is a common used method in animal study. I found that the pharmacokinetic of a drug given by IP was different to that by gavage. Apart from that the bioavailability of IP is higher than gavage, I wonder if there is any difference in the way the drug gets into the circulation between them. I think after IP injection, the majority of the drug was absorbed by veins of mesentery and then gathered into the portal vein of liver, which is similar to the pathway after gavage.
The main drawbacks of IP injection include:
- Drugs or vehicles may cause peritonitis
- Damage to organs by needles
- Injection into organs
- Though effective, generally restricted to laboratory animals
in addition to Daniele Ferreira:
... and the ip route is most useful for substances that are degraded in the GI tract and/or insufficiently absorbed.
Agree with Daniela Ferreira Sir but in my view oral route is better then ip because as we are taking about diseases now a days they occur by natural means...i.e by global environmental changes, environmental carcinogens present in environment and so on... so precaution is better then cure... for this in daily routine we take everything by po they effect much better then ip route... But as Ferreria Sir told ip route is fast.. thats true..
The IP injections were used in small animals in research. The advantage of this procceding with respect to gavage was the effects of gastric acid in the drug. I used insulin needles to avoid injury (perfurations) to the bowel.
When properly done, ip injection is easy and efficient and gives the same bioavailability as IV injection which is more cumbersom in mice. I injected thousands of mice with various anticancer drugs without problems. Gavage is oral, hence completely different and not comparable.
Absorb into the blood vessel through peritoneum. Bio-availability is almost similar to iv and greater than the oral. Most commonly used route in small laboratory animals as it is difficult to trace the vein so we cannot use iv, so ip can be used. Also ip is to avoid the drugs which are degraded by gastic juices and acid if given by oral. Some drawbacks are there that what Mr.pawan said mainly peritonitis and another is the careful aseptic conditions are needed.
I do agree to Vinoth , pawan.
To understand the difference between two routes you need to focus on this fundamental concepts of drugs routes of administration:
After oral administration, some compounds may be absorbed from the
mouth, and others from the stomach, but the majority are absorbed from
the intestine.
Drugs that are readily absorbed from the mouth include several steroid hormones, such as desoxycorticosterone acetate, and the vasodilator,
glycerol trinitrate. Salicylic acid, acetylsalicylic acid, and sodium thiopentone are absorbed more rapidly from the human stomach than ethanol, which was once considered exceptional in this respect.
Compounds absorbed from the gastro-intestinal tract are largely
transported via the portal vein directly to the liver where they may be biotransformed and/or partly secreted into the bile, or partly stored to be released only slowly.
On the other hand, some foreign compounds enter systemic circulation by absorption from the intestine into the lymphatics of the gut,thus delaying entry into the liver. Under normal conditions, little p-aminosalicylic acid or tetracycline were absorbed from the intestine into the lymphatics in rats: the difference in absorption potential between lymph and blood capillaries was ascribed to differences in rates of flow within the two circulating systems on the serosal side of the gut. Portal blood flow was about five hundred times faster than lymph flow.
By contrast, compounds absorbed from the mouth diffuse into the bloodstream and are not transported directly to the liver, and their biotransformation is thereby delayed. This route may be useful in prolonging the activity of a drug that is unstable in the gut or is readily biotransformed to inactive products in the liver. Similarly, much of an active drug administered intraperitoneally, a route usually used only for experimental purposes, quickly reaches the liver where it may be inactivated before entering systemic circulation. If administered intravenously or intramuscularly, it circulates in the blood before reaching the liver, thus enabling a larger proportion to reach its site of action. The route of administration can therefore be chosen according to the drug being used and the effects sought.
IP route Exclusively used for experimental purpose on Laboratory Animals (small) because of various difficulty as mentioned by Vinoth and to achieve successful out come of drug research due to accurate, reliable, convenient dosing with reproducible result renders by large absorbing surface area at the site of injection.
In compare to other available routes the % of distress is much lesser.
Kindly follow these few articles as mentioned for further clarification:
R. R. Levine and E. W. Pelikan, Ann. Rev. Pharmacol., 1964,4,69.
M. Gibaldi and J. L. Kanig, J. Oral. Therap. Pharmacol., 1965, 1, 440.
B. B. Brodie, J. Amer. Med. ASSOC1.,9 67, 202, 600.
T. J. De Marco and R. R. Levine, J. Pharmacol., 1969,169, 142.
I think you are correct. Because drug is absorbed through the diffusion into blood vessels from peritonium on injection. and the same in oral too, but the only diffrence is that here in i.p. absoption is from peritonium and in oral from g.i.t. The i.p. is used
-> to avoid the inconvenience in administering by i.v. in animals and
->To administer those with too rapid onset of action for i.v.
->to administer those which are less stable in g.i.t.
Anti-cancer drugs are often/mostly given via IV in humans. In animals, we use IP as its easy and doesn't harm the the mice much compared to PO or IV
hay, Ikhtifar, thank you for your answer. IP is a convenient alternative way for IV, but if the drug has liver first-pass effect, the route of IP will come to a different result compare to IV.
So when injected IP, does a drug actually "hit" the internal organs bathed by the intraperitoneal fluid?
@Florian: not reliably. Organs are covered by the peritonela membranes - most durug/substance will be absorbed from the peritoneal serous membranes, enter the blood stream there ang go via the portal system to the liver. You have a more direct effect e.g. on cancer cells that spread ON the peritoneal membranes - ovarian cancer would be a good example. Here i.p. application will directely hit the target. i.p. injection has been used as treatment for cancer patients (but the success is not overwhelming).
Thanks so much. What kind of penetration capability would a compound have to have to make it into the circulation from the ip cavity? I have an extremely charged compound (3 net negative charges). Would that still make it through?
I am guessing, as long as you have a solution, as long as you do not get precipitates (e.g. with proteins) I would give it a try. Resorption from i.p. is amazingly effective, e.g. phosphate (PO4) is quite charged, too.
I have a compound that only solubilizes in oil-based formulation. Does anyone know if it can be used for IV or only for oral. Thanks.
@Jian-Ting Zhang: As far as i know, IV requires only aqueous formulations.
Can anybody explain to me why the BBB concentration of a drug could be different after IV and IP injection (IV>IP) while plasma concentration is more or less the same for both routes?
Hello Dr.Huang,
Thanks a lot for very good question that is not easy to answer!
What we know these are general things about peritoneomu, great area and a great vascularization and therefore the adsorption surface, still have not dealt with this included also the!
Very good discussions and responses from which I learned a lot!
Will follow gladly respond because I am interested very pharmacokinetics of drugs given parenterally in the peritoneum particularly the cancer and the time spent in cirkulacion and, I think it depends on each individual substance T ½ half half time of elimination (50%) and the first pass through the liver!
Regards
We have seen that our Fenestra oil in water nanoemulsions can be administered IP for small animal micro-CT imaging but not our Mvivo BIS nanoparticles perhaps due to the viscosity of these agents. Another interesting consideration is whether there is a particle size cutoff. i.e. does the peritoneum filter out larger particles from entering the blood. Here is link for poster that describes the IP injection of the Fenestra contrast agent. Ref. http://www.medilumine.com/wp-content/uploads/2015/07/AMI-2006-Poster-244.pdf
Can IP in mice be done continuously over a period of 35 days? Is it Ethical?
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