Absorption, distribution, and elimination

Kinetic studies Rats/rniee One day to weeks Absorption, distribution, and elimination... 

Toxicokinetic—The study of the absorption, distribution and elimination of toxic compounds in the living organism. 

FIG. 2 Mechanisms of drug transfer in the cellular layers that line different compartments in the body. These mechanisms regulate drug absorption, distribution, and elimination. The figure illustrates these mechanisms in the intestinal wall. (1) Passive transcellular diffusion across the lipid bilayers, (2) paracellular passive diffusion, (3) efflux by P-glycoprotein, (4) metabolism during drug absorption, (5) active transport, and (6) transcytosis [251]. 

Abou-Donia MB, Suwita E, Nomeir AA. 1990a. Absorption, distribution, and elimination of a single oral dose of [14C]tri-orf/ o-cresyl phosphate in hens. Toxicology 61 13-25. 

The answers are 31-b, 32-a, 33-d (Katzung, pp 4—7.) The absorption, distribution, and elimination of drugs require that they cross various cellular membranes The descriptions that are given in the question define the various transport mechanisms. The most common method by which ionic compounds of low molecular weight (100 to 200) enter cells is via membrane channels. The degree to which such filtration occurs varies from cell type to cell type because their pore sizes differ. 

Simple diffusion is another mechanism by which substances cross membranes without the active participation of components in the membranes. Generally, lipid-soluble substances employ this method to enter cells. Both simple diffusion and filtration are dominant factors in most drug absorption, distribution, and elimination. 

With intraperitoneal administration, rats eliminated 28% of the original dose within 48 hours (Bull 1965), and mice eliminated 30 60% of the original dose within 96 hours (March et al. 1957). There appears to be insufficient toxicokinetic data to use as a basis for comparison of animals and humans. Additional studies comparing the rate and extent of absorption, distribution, and elimination in several different animal species after inhalation, oral, and dermal exposure to disulfoton could be useful. 

Benet LZ, Kroetz DL, Sheiner LB. 1995. Pharmacokinetics The dynamics of drug absorption, distribution and elimination. In Hardman JG, Gilman, AG, Limbird LE, eds. Goodman Gilman s The pharmacological basis of therapeutics, 9th ed. New York, New York McGraw Hill. 

M. B. Abou-Donia, E. Suwita, A. A. Nomeir, Absorption, Distribution, and Elimination of a Single Dose of [14C]Tri-o-cresol Phosphate in Hens , Toxicology 1990, 61, 12-25. 

The pharmacokinetics of hypericin and pseudohypericin piasma have been studied as weii (Brockmoiier et ai. 1997). Human subjects receiving piacebo, or 900, 1800, or 3600 mg of a standardized hypericum extract (LI 160), which contained 0, 2.81, 5.62, and 11.25 mg of totai hypericin and pseudohypericin, achieved maximum total plasma concentrations at 4 hours (0.028, 0.061, and 0.159 mg/L, respectively). The half-lives of absorption, distribution, and elimination were 0.6, 6.0, and 43.1 hours, respectively, using 750 pg of hypericin, and are slightly different for 1578 pg of pseudohypericin (1.3, 1.4, and 24.8 hours, respectively) (Kerb et ai. 1996). The systemic availability of the hypericum extract LI 160 is between 14 and 21%. Comparable results are found in another study using LI 160 (Staffeldt et ai. 1994). Long-term dosing of 3 x 300 mg per day showed that steady-state levels of hypericin are reached after 4 days. 

Benet LZ, Sheiner LB. 1985. Pharmacokinetics The dynamics of drugs absorption, distribution, and elimination. In 7th ed. Goodman s and Gilman s The pharmaceutical basis of therapeutics. New York, NY MacMillan Publishing Company. 

Further, drug absorption, distribution, and elimination from the body may vary due to differences in protein binding, enzymic modification, etc, since proteins are also chiral entities (see Chapter 13). 

The hydrophobic interior of the phospholipid membrane constitutes a diffusion barrier virtually impermeable for charged particles. Apolar particles, however, penetrate the membrane easily. This is of major importance with respect to the absorption, distribution, and elimination of drugs. 

If after single dose administration, the blood samples are not collected at time intervals, which allow for a description of the whole plasma concentration time course, including the absorption, distribution, and elimination phase, the information obtained is limited. In particular, data should be available in the hrst hours after administration to cover the absorption phase. If measurements of the parent compound and its metabolite(s) are made in this period, this will allow assessment of an extensive first pass effect, i.e., when a substance after oral administration is transported via the portal vein to the liver where metabolism takes place before the substance enters the systemic circulation. 

McCollister DD, Beamer WH, Atchison GJ, et al. 1951. The absorption, distribution and elimination of radioactive carbon tetrachloride by monkeys upon exposure to low vapor concentrations. J Pharmacol Exp Therap 102 112-124. 

Fig. 2. Illustration of absorption, distribution and elimination processes of drugs in the blood circulation.

Kinetic Parameters for Nickel Absorption, Distribution, and Elimination in Humans 2-7 Genotoxicity of Nickel in Vivo... 

Studies of dmg absorption, distribution and elimination comprise what is referred to as pharmacokinetics. By contrast, the concentration of a pharmaceutical compound at the site(s) of action in relation to the magnitude of its effect(s) is referred to as pharmacodynamics. Both pharmacokinetics and pharmacodynamics have their roots in physiology, chemical kinetics, biochemistry, and pharmacology. They seek to provide a mathematical basis of the absorption, distribution, metabolisms, and... 

Pharmacokinetic processes govern the absorption, distribution, and elimination of drugs and are of great practical importance in the choice and administration of a particular drug for a particular patient, eg, a patient with impaired renal function. The following paragraphs provide a brief introduction to pharmacodynamics and pharmacokinetics. 

The relationship between dose and effect can be separated into pharmacokinetic (dose-concentration) and pharmacodynamic (concentration-effect) components. Concentration provides the link between pharmacokinetics and pharmacodynamics and is the focus of the target concentration approach to rational dosing. The three primary processes of pharmacokinetics are absorption, distribution, and elimination. 

Increased susceptibility to the pharmacologic or toxic activity of drugs has been reported in very young and very old patients compared with young adults (see Chapters 59 and 60). Although this may reflect differences in absorption, distribution, and elimination, differences in drug metabolism also play a role. Slower metabolism could be due to reduced activity of metabolic enzymes or reduced availability of essential endogenous cofactors. 

Pharmacologic factors include (1) the kinetics of absorption, distribution, and elimination (2) the ability of the drug to be delivered to the site of infection (3) the potential toxicity of an agent and (4) pharmacokinetic or pharmacodynamic interactions with other drugs. 

Goldstein A, Aronow L, Kalman SM (1968) The absorption, distribution and elimination of drugs — passage of drugs across the placenta. In Goldstein A, Aronow L, Kalman SM ed. Principles of drug action the basis of pharmacology. New York, Harper and Row, p 179. 

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