individuals with atrophic gastritis (Russell 2001), and in this case, the absorption

process itself is hardly affected. Decreased iron absorption has been reported in

achlorhydric subjects, as stomach acid serves to keep iron in ferric form until it

reaches the absorptive sites in duodenal mucosa. Ascorbate can chelate ferric ions

and increase absorption at neutral or slightly alkaline pH range. However, heme-iron

(found in meat) does not get affected by lack of acid and is thus normally absorbed in

subjects with atrophic gastritis. In elderly persons, reduced absorption of calcium is

linked with decreased vitamin D absorption and lesser synthesis in skin, as well as

decreased vitamin D receptor expression in the intestinal epithelial cell, and impaired

conversion of 25-hydroxy vitamin D to the active hormonal form 1,25-dihydroxy

vitamin D (Holick et al. 1989).

Arguably, elderly subjects do not maldigest or malabsorb macronutrients because

they usually have a large reserve capacity of both the pancreas and small intestine.

Therefore, taking into consideration the total pancreatic reserve capacity and total

length of the small intestine, the small digestive decreases of macronutrients become

clinically irrelevant (Russell 2001). In elderly individuals with achlorhydria second-

ary to atrophic gastritis, the orally administered drugs like ketoconazole, ampicillin,

and H2 antagonists, which require acidic environment for absorption, may show low

absorption or diminished efficiency of proton pump inhibitors (Hurwitz et al. 1997).

Compared to younger subjects, elderly individuals often show >25% increase in

bioavailability of orally administered drugs due to reduced first pass hepatic metab-

olism (Wilkinson 1997), thereby suggesting the need for dose adjustment in the

elderly patients. On the other hand, higher doses of prodrugs (e.g., codeine, propran-

olol, enalapril, perindopril, simvastatin) may be required in geriatric patients to

obtain the desired AUC for the active drug as opposed to the younger individuals

(Hilmer 2008). Elevated levels of gastric pH in the elderly with atrophic gastritis

may also affect the bioavailability of formulations that rely on low pH to dissolve an

external coat. The formulations of constant drug delivery rate that are independent of

pH or gastrointestinal motility may be less affected by ageing (Hilmer 2008).

15.6

Distribution

Orally administered xenobiotics reach the circulation either free or bound to blood

proteins, mainly albumin or alpha-1-acidic glycoproteins (i.e., bound drug fraction).

In geriatric patients, albumin content of plasma is generally low due to the dimin-

ished liver function that increases unbound fraction of drugs for distribution. This

phenomenon influences distribution properties of highly albumin-bound drugs like

phenytoin, coumarins, and pethidine. The transfer of a drug from circulation or

central compartment to the peripheral tissue compartments is called volume of

distribution. Volume of distribution (Vd) is defined as the apparent volume into

which the drug distributes to achieve the desired therapeutic plasma concentration. It

is a proportionality constant related to the amount of administered drug in the body

and the concentration of drug in the reference fluid (e.g., whole blood or plasma). Vd

depends on the plasma protein binding, lipid to water partition coefficient,

240

M. Bhaskar et al.