Incomplete absorption

Two-compartment catenary model for extravascular administration with incomplete absorption... 

The effect of incomplete absorption is that only a fraction of a single-dose D is made available to the central plasma compartment. The solution of the previous model needs, therefore, to be modified by replacing the term D by F D. Consequently the area under the curve AUCg under incomplete extravascular absorption will be smaller than the maximal AUC that results from complete absorption. The latter, as we have seen is equal to the AUC obtained from a single intravenous injection, which we denote by AUC,. These considerations can be summarized as follows ... 

Mucin, a viscous mucopolysaccharide that lines and protects the intestinal epithelium, has been thought to bind certain drugs nonspecifically (e.g., quarternary ammonium compounds) and thereby prevent or reduce absorption. This behavior may partially account for the erratic and incomplete absorption of such charged... 

In man, the oral bioavailability of UK-224,671 is less than 10% [39]. Since clearance of UK-224,671 is low relative to liver blood flow, the poor oral bioavailability is due to incomplete absorption of the compound from the GIT. Caco-2 flux experi-... 

Another therapeutic class to be briefly discussed is that of the lipid-lowering agents known as fibrates, e.g., clofibrate and fenofibrate (8.5). Here also, the acidic metabolite is the active form clofibrate (an ethyl ester) is rapidly hydrolyzed to clofibric acid by liver carboxylesterases and blood esterases [11], Human metabolic studies of fenofibrate (8.5), the isopropyl ester of fenofibric acid, showed incomplete absorption after oral administration, while hydrolysis of the absorbed fraction was quantitative [12], This was followed by other reactions of biotransformation, mainly glucuronidation of the carboxylic acid group. 

A drug can be administered directly into the vascular compartment or by an alternative route, such as orally. It can usually be assumed that the entire dose administered by the intravenous route reaches the systemic circulation. After oral administration, only a proportion may reach the systemic circulation because of incomplete absorption or because absorbed drug may be metabolised in the mucosa of the gastrointestinal... 

Oral bioavailability is one of principal pharmacokinetic properties in drug discovery. It represents the percentage of an oral dose that is available to produce pharmacological actions, in other words, the fraction of the oral dose that reaches the system circulation in an active form. By the definition, when a drug is administered intravenously, its bioavailability is 100%. However, when a medication is administered via other routes, especially orally, its bioavailability decreases due to incomplete absorption and first-pass metabolism. 

Mecfianism of Action An ergotamine derivative, alpha-adrenergic blocker that directly stimulates vascular smooth muscle. May also have antagonist effects on sero-fonin. Therapeutic Effect Peripheral and cerebral vasoconstriction. Pharmacokinetics Slow, incomplete absorption from the gastrointestinal (GI) tract rate of absorption of intranasal route varies. Protein binding greaterthan 90%. Undergoes extensive first-pass metabolism in liver. Metabolized to active metabolite. Eliminated in feces via biliary system. Half-life 7-9 hr. 

Pharmacokinetics Variable, incomplete absorption from the GI tract. Protein binding greater than 99%. Widely distributed. Deiodinated in peripheral tissues, minimal metabolism in the liver. Eliminated by biliary excretion. Half-life 6-7 days. 

Pharmacokinetics Rapid and incomplete absorption following PO administration. Protein binding 94%. Rapidly excreted as unchanged drug in urine. Half-life 30 min. 

Propylthiouracil is rapidly absorbed, reaching peak serum levels after 1 hour. The bioavailability of 50-80% may be due to incomplete absorption or a large first-pass effect in the liver. The volume of distribution approximates total body water with accumulation in the thyroid gland. Most of an ingested dose of propylthiouracil is excreted by the kidney as the inactive glucuronide within 24 hours. 

Pass the solution through the column at a rate of 5 ml/min, and then wash the column with 50 ml of hot water to remove the mineral acid. Check the completeness of absorption of tbe copper and cadmium ions. For tbis purpose, pour 3-5 ml of the washing water into a test tube and add a solution of ammonium sulphide or hydrogen-sulphide water to it. The formation of a precipitate indicates incomplete absorption, which occurs only if there is an error in performing the operations described above. In this case, the experiment has to be repeated. To do tbis, wash the column with a solution of hydrochloric acid (1 3), next with water until the washing solution has a neutral reaction, and then pass the solution through the column again. 

When a compound is administered by a route other than intravenously, the plasma level profile will be different, as there will be an absorption phase, and so the profile will be a composite picture of absorption in addition to distribution and elimination (Fig. 3.26). Just as first-order elimination is defined by a rate constant, so also is absorption kab. This can be determined from the profile by the method of residuals. Thus, the straight portion of the semilog plot of plasma level against time is extrapolated to the y axis. Then each of the actual plasma level points, which deviate from this during the absorptive phase, are subtracted from the equivalent time point on the extrapolated line. The differences are then plotted, and a straight line should result. The slope of this line can be used to calculate the absorption rate constant kab (Fig. 3.26). The volume of distribution should not really be determined from the plasma level after oral administration (or other routes except intravenous) as the administered dose may not be the same as the absorbed dose. This may be because of first-pass metabolism (see above), or incomplete absorption, and will be apparent from a comparison of the plasma... 

Antacid preparations based on aluminium hydroxide sometimes contain magnesium salts (and carbonate or oxide) to offset the constipating effect of the alumina. This laxative effect of salts such as magnesium sulphate (or citrate) and other saline cathartics such as potassium sodium tartrate is due to their incomplete absorption from the digestive tract so that, by osmotic forces, they retain water in the intestinal lumen. 

Depends on electron fraction of substrate. Most energy will be deposited in solvent. Incomplete absorption of quantum. 

Rectal Alternative to oral route local effect on rectal tissues Poor or incomplete absorption chance of rectal irritation Laxatives suppository forms of other drugs... 

Chemical synthesis produces dyes of varying particle size. When the dyes are applied in this form, uneven and spotty dyeing results, and the dyeing process may be slow and frequently accompanied by incomplete absorption [46], To assure high yield, good reproducibility, and faultless dyeing and printing in commercial use, especially when densely woven fabric or wound material is involved, the dye must be applied as a fine dispersion that is stable under the process conditions. 

All orally administered chugs must pass through the gastrointestinal tract to reach the blood and thus pass the barrier formed by the enterocytes in the intestine. For years, low first-pass bioavailability of a drug was attributed mainly to clearance via hepatic metabolism and biliary clearance or incomplete absorption in the intestine due to poor solubility or intrinsic permeability properties. Although these are important factors in determining the overall oral bioavailability of certain... 

It can be seen that amounts of up to a few grams can be converted in 5-10 h in the case of complete absorption and unitary quantum yield (ignoring any internal filter effect). Lower quantum yields or an incomplete absorption proportionally lengthens the time required for the transformation. It is most likely safe to say that exploratory reactions on the 100 mg scale can be carried out in a reasonable time, provided that > 0.1-0.05. Even reactions with a quantum yield at the lower limit or below may be interesting for a preparation if the reaction is clean. Given the minimal safety... 

For incomplete absorption of the primary blue light by the LUCO material, also mixed bluish-greenish (i.e. turquoise) colours can be generated. Additive colour mixing of the primary LED-blue with secondary photoluminescence-red results in magenta, a colour not accessible by conventional pn-junction semiconductor devices. 

---