Dear Claire, in pharmacokinetic and pharmacodynamic studies, the body usually is separated into different compartments that have different transfer functions for the passage of a drug (different animal models are described elsewhere in the literature). There are several reasons for a disappearance of drugs from the peritoneal cavity upon injection and for the delay a drug reaches the target area. Reasons can be for example diffusion into the surrounding tissues, the compound may be carried away by capillary blood or lymph, metabolized by tissue enzymes or bound to tissue proteins. So basically, one needs to consider a schematic block diagram of the absorption pathways for small and macromolecules from the peritoneal cavity to systemic circulation up to the brain (e.g. i.p. injection, peritoneal cavity, interstitium, capillaries, blood-brain barrier, etc.). You are right when you state that “…how fast the drug reaches the brain will highly depend on the nature of the drug, and probably many other factors…”. The drug has to pass different barriers and each barrier has a different time constant. Shoyaib et al. have published a paper concerning this matter in 2019 (Abdullah Al Shoyaib , Sabrina Rahman Archie , Vardan T Karamyan; Intraperitoneal Route of Drug Administration: Should it Be Used in Experimental Animal Studies?; Pharm Res (2020) 37: 12; https://doi.org/10.1007/s11095-019-2745-x). In this paper the authors discussed, if intraperitoneal route of drug administration should be used in experimental animal studies. The authors summarize the main mechanisms involved in bioavailability of i.p. administered drugs and provide examples of pharmacokinetic profiles for small and large molecules in comparison to other routes of administration. For example, the authors describe, that following rapid absorption from the peritoneal cavity, a compound may face one of the following two pathways to reach systemic circulation: 1) it is absorbed through the visceral peritoneum, the mesentery and omentum and is drained into portal circulation, or 2) the compound gets into the systemic circulation directly bypassing liver when it is absorbed through parietal peritoneum and lymphatics. As you can see there are many factors influencing the passage of an i.p. administered drug through all body compartments and therefore I think it is difficult to determine a reproducible general minimum time it takes for an i.p. injected drug to reach the brain. I hope that this paper will help you to answer your question. Good luck, Dirk

Thank you for the detailed response and for the paper reference, will have a look!

Hello Claire, I also perform in vivo electrophysiology with serotonergic drugs and see the response within 2-5 minutes from i.p. injection.

Antonio