Drug absorption, distribution and excretion

Depends a lot on tbs pK of drug and pH erf environment. Unionized drug is much more lipid soluble than ionized drug 

If a drug is given by intravenous injection, it enters the blond and is mpiilly disirihuted to the tissues. By laking repealed blood sample.s. the 

Uptake by the liver and subsequent elimination in the bile (solid line from liver). 

A process that depends on the conceiitration at any given time is called lirst iirder and mosl drugs exhibit lirst-urder elimination kinetics. If any enzyme System responsible for drug metabolism becomes saturated, then the elimination kinetics change lo zero order, i.e. the rate of elimination procccd.s at a constant rate and is unaffected by an 

Drugs can be administered orally or parenierally (i.e. by a non-giisirointesiinal route I. 

---

Ayrton, A., Morgan, P., Role of transport proteins in drug absorption, distribution and excretion, Xenobiotica 2001, 31, 469-497. 

FACTORS SUCH AS CHARGE THAT AFFECT DRUG ABSORPTION, DISTRIBUTION, AND EXCRETION... 

Reed, M.D. The ontogeny of drug disposition Focus on drug absorption, distribution, and excretion. Drug Inform. J. 1996, 30, 1129-1134. 

ABC Transporters Involved in Drug Absorption, Distribution, and Excretion... 

Historically, drug absorption, distribution, metabolism, excretion, and toxicity ADMET) studies in animal models were performed after the identification of a lead compound. In order to avoid costs, nowadays pharmaceutical companies evaluate the ADMET profiles of potential leads at an earlier stage of the development... 

It was apparent that the FDA recognized the ability of the pharmaceutical industry to develop chiral assays. With the advent of chiral stationary phases (CSPs) in the early 1980s [8, 9], the tools required to resolve enantiomers were entrenched, thus enabling the researcher the ability to quantify, characterize, and identify stereoisomers. Given these tools, the researcher can assess the pharmacology or toxicology and pharmacokinetic properties of enantiopure drugs for potential interconversion, absorption, distribution, and excretion of the individual enantiomers. 

Kerberle, H. (1971). Physicochemical factors of drugs affecting absorption, distribution and excretion. Acta Pharmacol. Toxicol. 29 (Suppl 3) 30-47. 

Drug metabolism has been recognized as one of the key factors in the discovery of new chemical entities. A lead compound needs to not only interact with the target enzyme/receptor but also remain over a certain threshold concentration at the site of action for a defined period to produce the desired therapeutic effect. Drug metabolism together with absorption, distribution and excretion are among the factors that influence the final time-concentration relationship of drugs and therefore the potential efficacy of the compound [1],... 

In addition to phase I and phase II enzymes, equally important is a group of transporter proteins expressed in various tissues, such as the liver, intestine, brain and kidney, which modulate the absorption, distribution and excretion of many drugs. 

Chu I, Villeneuve DC, Secours V, et al. 1979b. The absorption, distribution and excretion of photomirex in the rat. Drug Metab Dispos 7 24-27. 

Differences in clinical effectiveness are partly due to differences in absorption, distribution and excretion of the individual drugs. In general tetracyclines are absorbed irregularly from the gastrointestinal tract and part of the dose remains in the gut and is excreted in the faeces. However this part is able to modify the intestinal flora. Absorption of the more lipophilic tetracyclines, doxycycline and minocycline is higher and can reach 90-100%. The absorption is located in the upper small intestine and is better in the absence of food. Absorption is impaired by chelation with divalent cations. In blood 40-80% of tetracyclines is protein bound. Minocycline reaches very high concentrations in tears and saliva. Tetracyclines are excreted unchanged, in both the urine by passive filtration and in the feces. Tetracyclines are concentrated in the bile via an active... 

Chasseaud LF. Processes of absorption, distribution and excretion. In Hathway DE, Brown SS, Chasseaud LF, et al. Foreign Compound Metabolism in Mammals, Vol. 1. London The Chemical Society, 1970. Findlay JWA. The distribution of some commonly used drugs in human breast milk. Drug Metab Rev 1983 14 653. 

Many of the drug monographs contain a new section entitled Disposition in the Body. This section details die absorption, distribution, and excretion of the drug, notes the major metabolites and therapeutic and toxic plasma concentrations, and gives values for pharmacokinetic parameters such as half-life, volume of distribution, clearance, and protein binding. In addition, abstracts from published clinical studies and case histories are included. 

Tetracycline was discovered after a team of workers examined 100000 soil samples from around the world. Tetracycline derivatives include chlor-tetracycline, oxytetracycline, doxycycline and minocycline. The tetracyclines have a broad spectrum of activity they are effective against Grampositive and Gram-negative bacteria, some anaerobes. Chlamydia, Mycoplasma, Ehrlichia and Rickettsia spp. and some protozoa. Their activity against staphylococci is usually limited and they are not active against enterococci. E. coli, Klebsiella, Proteus and Pseudomonas spp. are usually resistant. Doxycycline and minocycline are usually more active in vitro than the other tetracyclines. Differences in the clinical efficacy of the tetracyclines can be attributed to differences in the absorption, distribution and excretion of the individual drugs rather than to differences in bacterial susceptibility. 

Almost all drug-macro molecule interactions occurring in the body show chiral discrimination. This is true whether they are drug-enzyme or drug-receptor in nature. The situation is complicated further because some drugs show stereoselective absorption, distribution and excretion between enantiomers and it is difficult to determine which effects are due solely to metabolism and which are due to other biopharmaceutical factors. 

It is crucial that plasma concentrations of drug are measured in these studies to allow for determination of effects on the basis of exposure. Frequently this is a more appropriate measure of comparing effects in animals and man, as rates of absorption, distribution and excretion can vary extensively between these species. This aspect, now commonly referred to as toxicokinetics , has been outlined in an ICH guideline (Federal Register, 1 March 1995). This guideline specifies minimum requirements in terms of number of time points examined, number of animals per time point, and the requirements for calculation of various pharmacokinetic parameters such as Umax, AUC and so on. These will become important... 

This edition incorporates a new trend in drug discovery namely the consideration of pharmacokinetics and ADME properties of drugs (absorption, distribution, metabolism, excretion) early in the process. As prospective new drugs are tested in more complex systems (with... 

Szakacs, G., Varadi, A., Ozvegy-Laczka, C, and Sarkadi, B. (2008) The role of ABC transporters in drug absorption, distribution, metabolism, excretion and toxicity (ADME-Tox). Drug Discovery Today. 13, 379-393. 

Note that several among the factors listed above influence not only biotransformation, but can also affect absorption, distribution and excretion by interacting with transporters and therapeutic effects by influencing drug targets. 

Dodson WE, Rust RS. Phenobarbital Absorption, distribution, and excretions In Levy R, Mattson R, Meldrum B, eds. Antiepileptic Drugs, 4th ed. New York, Raven Press, 1995 379-387. 

---