Expanded Answers for Study Problems in: Rowland & Tozer's Clinical Pharmacokinetics: Concepts and Applications, 3rd edition.

Chapter 9 - Absorption

Study Problems on Page 135

1. Since most xenobiotics are absorbed in the small intestine, if the transit time through the intestine is very short (as in a hypermotility syndrome), there will be insufficient time for absorption to occur - resulting in a reduced extent of bioavailability. Also, some xenobiotics are unstable in the gastrointestinal environment (e.g., the acidic environment of the stomach) and degrade in the intestinal tract - also resulting in a reduced extent of bioavailability. Finally, numerous xenobiotics are metabolized by enzymes located in the intestinal wall or liver, resulting in a reduction in the amount of parent compound which reaches the systemic circulation.

5. The answer in the textbook is somewhat confusing. The statement is generally true that absorption of a solution from the muscle is slower than from the small intestine. There are times, however, when a solution will be absorbed more rapidly from the muscle than from the small intestine. An example would be a large polar molecule. Such a compound would be poorly absorbed across the tightly knit intestinal membrane. In contrast, the capillary bed of the muscle is more loosely knit and polar compounds are more readily absorbed. The example given in Rowland and Tozer is gentamicin. Gentamicin, which is a large polar molecule, is not absorbed after oral administration but is available after intramuscular administration. The last statement in the book on the answer to this question states, "Other exceptions are drugs that precipitate at the injection site, from which dissolution is very slow". Obviously, if a drug precipitates at the injection site it is not an exception to the statement that a solution of a drug is generally absorbed more slowly from the muscle than from the small intestine - it is an example of a case where absorption would slower from the IM site.

You should recognize that clinically the comparison which is usually made is that between IM administration of a solution and oral administration of a tablet or capsule. When a water soluble drug is given by these routes, the onset for IM administration of the solution will generally be more rapid than the oral administration of a tablet. At times, however, one may find little difference between the IM and oral routes. It is amazing how quickly some drugs are absorbed after oral administration.

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