Absorption pharmacology

N Ammoury, H Fessi, JP Devissaguet, M Du-brasquet, S Benita. Jejunal absorption, pharmacological activity, and pharmacokinetic evaluation of indomethacin-loaded poly(d,l-lactide) and poly(-isobutyl-cyanoacrylate) nanocapsules in rats. Pharm Res 8 101-105, 1991. 

DivoU M, Greenblatt DJ. Alcxihol does not enhance diazepam absorption Pharmacology (1981) 22,263-8. 

Phase I. This involves general testing for human pharmacology in healthy volunteers, ie, safe-dose adjustment deterrnination of absorption, metabohsm, and excretion patterns and monitoring for side effects. Usually fewer than 10 test subjects ate involved. 

Care should be exercised when attempting to interpret in vivo pharmacological data in terms of specific chemical—biological interactions for a series of asymmetric compounds, particularly when this interaction is the only parameter considered in the analysis (10). It is important to recognize that the observed difference in activity between optical antipodes is not simply a result of the association of the compound with an enzyme or receptor target. Enantiomers differ in absorption rates across membranes, especially where active transport mechanisms are involved (11). They bind with different affinities to plasma proteins (12) and undergo alternative metaboHc and detoxification processes (13). This ultimately leads to one enantiomer being more available to produce a therapeutic effect. 

Up to 80% of oral doses of ascorbic acid are absorbed in humans with intakes of less than 0.2 g of vitamin C. Absorption of pharmacological doses ranging from 0.2 g to 12 g results in an inverse relationship, with less than 20% absorption at the higher doses. A single oral dose of 3 g has been reported to approach the absorptive capacity (tissue saturation) of the human intestine. Higher blood levels can be attained by providing multiple divided vitamin C doses per day. 

The pharmacology of penicillins differs markedly from compound to compound but has been well reviewed (57). The majority of derivatives, including penicillin G and the antipseudomonal penicillins, ate unstable in gastric acid and ate not available orally. The isoxazolyl penicillins ate relatively acid stable but not consistendy well absorbed by the oral route. Nafcillin and oxacillin ate poody absorbed orally cloxacillin, dicloxacillin, and ducloxacillin ate more teUable. Penicillin V, ampicillin, and patticulady amoxicillin ate relatively well absorbed orally. Esters of ampicillin such as bacampicillin, pivampicillin, and talampicillin improve the level of oral absorption of ampicillin to that achieved by amoxicillin. Absorption can be diminished by food after oral adruinistration, however, and peak blood levels, usually achieved after 1 to 2 h, ate somewhat delayed after ingestion of food. 

Because digitoxin is a nonpolar, lipophilic glycoside, absorption from the GI tract is complete. About 90% of the dmg in plasma is tightly bound to protein. It is metabolized in the Hver to many metaboHtes, including digoxin which is the only pharmacologically active metaboHte. The dmg is excreted via the bile into feces. The elimination half-life of digitoxin is seven to nine days (87). 

Nicardipine is almost completely absorbed after po adrninistration. Administration of food decreases absorption. It undergoes extensive first-pass metaboHsm in the Hver. Systemic availabiHty is dose-dependent because of saturation of hepatic metaboHc pathways. A 30 mg dose is - 35% bioavailable. Nicardipine is highly protein bound (>95%). Peak plasma concentrations are achieved in 0.5—2.0 h. The principal path of elimination is by hepatic metaboHsm by hydrolysis and oxidation. The metaboHtes are relatively inactive and exert no pharmacological activity. The elimination half-life is 8.6 h. About 60% of the dose is excreted in the urine as metaboHtes (<1% as intact dmg) and 35% as metaboHtes in the feces (1,2,98,99). 

Absorption after po dosing is fairly complete. It undergoes extensive first-pass metaboHsm in the Hver and is 60% bioavailable. It is extensively bound (99%) to a -acid glycoproteins. Bepridil is almost completely metaboli2ed in the Hver. Seventeen metaboHtes have been identified but only the 4-hydroxy-A/-phenyl-bepridil has some pharmacological activity. The elimination half-life is 33—42 h (107). 

In view of the strychnine-like pharmacological action recorded for gelsemine, Janot and Berton have compared the ultra-violet absorption spectra of the two alkaloids, which proved to be remarkably similar. That of sempervirine was quite different and also unlike those of indole, quinoline and cinchonamine, with which it was also compared. 

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. 

The overall objective of clinical trials is to establish a drug therapy that is safe and effective in humans, to the extent that the risk-benefit relationship is acceptable. The ICH process has developed an internationally accepted definition of a clinical trial as Any investigation in human subjects intended to discover or verify the clinical, pharmacological and/or other pharmacodynamic effects of one or more investigational medicinal product(s), and/or to identify any adverse reactions to one or more investigational medicinal product(s) and/or to study absorption, distribution, metabolism and excretion of one or more investigational medicinal product(s) with the object of ascertaining its (their) safety and/or efficacy. ... 

Oral absorption and bioavailability, prediction of, 41 (2003) 1 Organophosphorus pesticides, pharmacology of, 8 (1971) 1 Oxopyranoazines and oxopyranoazoles,... 

Liothyronine (Cytomel ) SyntheticT3 5, 25, and 50 meg tablets 15 meg Rarely needed in treatment of hypothyroidism rapid absorption and pharmacologic effect increased toxicity versus LT4 no outcome benefit to combining with LT4... 

The pharmacology and toxicology of certain economic poisons have been developed to a degree which surpasses investigations of any other class of nonmedicinal compounds. In certain instances more is known concerning the site and mechanism of action, the absorption, distribution, and excretion of these substances than is known concerning some of the more commonly used pharmaceutical compounds. This has come about as a result of the conscientious recognition of the public health hazards which are inherent in the economic poisons. 

In general, one finds that the more rapid and complete the absorption, the more uniform and reproducible the pharmacological response becomes. 

RG Crounse. Human pharmacology of griseofulvin. The effect of fat intake on gastrointestinal absorption. J Invest Dermatol 37 529-533, 1961. 

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