Absorption clinical factors

In the first edition of this encyclopedia the section on absorption covered a range of topics that included discussion of the cell membrane, parenteral and enteral absorption, clinical factors, and pharmacokinetic characterization of absorption. 

Clinical manifestation of vitamin B 2 deficiency is usually a result of absence of the gastric absorptive (intrinsic) factor. Dietary deficiency of vitamin B 2 is uncommon and may take 20 to 30 years to develop, even in healthy adults who foUow a strict vegetarian regimen. An effective enterohepatic recycling of the vitamin plus small amounts from bacterial sources and other contaminants greatly minimizes the risk of a complete dietary deficiency. Individuals who have a defect in vitamin B 2 absorption, however, may develop a deficiency within three to seven years. 

Reigelman, S. (1974) Pharmacokinetics pharmacokinetic factors affecting epidermal penetration and percutaneous absorption. Clinical Pharmacology and Therapeutics, 16, 873-883. 

The most useful pharmacokinetic variable for describing the quantitative aspects of all processes influencing the absorption (fa) and first-pass metabolism and excretion (Eg and Eh) in the gut and liver is the absolute bioavailability (F) [40]. This pharmacokinetic parameter is used to illustrate the fraction of the dose that reaches the systemic circulation, and relate it to pharmacological and safety effects for oral pharmaceutical products in various clinical situations. The bioavailability is dependent on three major factors the fraction dose absorbed (fa) and the first-pass extraction of the drug in the gut wall (EG) and/or the liver (EH) (Eq. (1)) [2-4, 15, 35] ... 

Aqueous solubility, potency and permeability are three factors under medicinal chemistry control that must be optimized to achieve a compound with acceptable oral absorption. Typically, a lead (chemistry starting point) is deficient in all three parameters. The inter-relationships of these three parameters has been described in a series of publications from Pfizer researchers [7, 8]. Figure 9.1 depicts graphically the minimum acceptable solubility as a function of projected clinical potency and intestinal permeability. A minimum thermodynamic aqueous solubility of 52... 

Understanding the factors influencing drug absorption and in particular predicting these values on the basis of pre-clinical in vitro and in situ experiments remains crucial to bringing safe and effective drugs to the market [3],... 

An increasing number of preclinical and clinical studies have been conducted in recent years aiming to clarify the barrier function of the colonic epithelium in more detail and to devise drug delivery strategies, for example, by modulating factors limiting colonic drug absorption. For preclinical... 

Foreign clinical results are acceptable except in areas where there are immunological and ethnic differences between Japanese and foreigners. The ethnic factors are divided into two components intrinsic factors such as racial factors and physiological differences and extrinsic factors, which include cultural and environmental issues. In these cases, the MHLW may require that some bridging comparative clinical trials be performed with dose ranging protocols. This will enable absorption, distribution, metabolism, and excretion studies to be carried out on Japanese individuals and provide better dosage and indication for the Japanese people. The MHLW also requires that application be accompanied by one year of real-time stability data and that sterility test results be included. 

Define objectives of treatment before initiation of a drug Note frequency and severity for a drug Dependant on age, disease, and individual patient factors Include drug action, absorption, elimination, and protein binding Are they clinically significant ... 

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