Age-Related Changes in the Gastrointestinal System

Abstract

Although there are many changes in the gastrointestinal tract with aging, only those in the liver substantially influence blood concentrations and clearance of drugs. The liver mass, overall function, and blood flow decrease approximately 1% per year after age 40 to 50 years, and accordingly, the hepatic metabolism or clearance of drugs decreases in this proportion. The sensitivity of the gastrointestinal tract to usual concentrations of drugs is increased, and this, in part, accounts for the increased frequency of adverse drug reactions in elderly patients.

Aging Biology and Geriatric Clinical Pharmacology

“…Any aging effects on gastric acid secretion is likely to be confounded by Helicobacter pylori eradication and the widespread use of proton pump inhibitors and H 2 -receptor antagonists among older people. The drugs that require an acidic environment to become ionized (e.g., ketoconazole, ampicillin esters, iron compounds) will be affected most by any age-related changes in gastric acid production (Iber et al, 1994).…”

“…Most in vivo studies of aging and drug metabolism in humans have involved simple pharmacokinetic investigations that report the elimination of a single drug in vivo (Vestal et al, 1978;Mooney et al, 1985;Durnas et al, 1990). Although there is considerable variability in the results of these studies reflecting confounding factors such as frailty (Woodhouse, 1992;Owens et al, 1994), comorbidity, polypharmacy, smoking, and alcohol intake altered nutrition (Vestal et al, 1978;Kitani, 1986;Iber et al, 1994) and enzyme induction (Kinirons and Crome, 1997); it is possible, nevertheless, to determine whether the effect of age on drug metabolism is secondary to age-related changes in blood flow, protein binding, enzyme activity, or liver size (Le Couteur and McLean, 1998).…”

Pharmacokinetic Variability of Routinely Administered Bisoprolol in Middle-Aged and Elderly Japanese Patients

“…6) In addition, hepatic drug metabolism may be diminished due to decreases in hepatic blood flow, liver mass, and levels of cytochrome P450 (CYP) drug-metabolizing enzymes. 7,8) However, the pharmacokinetics of bisoprolol has not been clarified in routinely treated elderly Japanese patients.The present study was designed to evaluate the pharmacokinetic variability of routinely administered bisoprolol in middle-aged and elderly Japanese patients. A pharmacokinetic analysis was performed using a nonlinear mixed effects model (NONMEM).…”

“…6) In addition, hepatic drug metabolism may be diminished due to decreases in hepatic blood flow, liver mass, and levels of cytochrome P450 (CYP) drug-metabolizing enzymes. 7,8) However, the pharmacokinetics of bisoprolol has not been clarified in routinely treated elderly Japanese patients.…”

Magnetic resonance diffusion-weighted imaging: quantitative evaluation of age-related changes in healthy liver parenchyma

“…Subsequently, we have firstly investigated the possible correlation between age and ADC values of the liver without finding out any significant correlation, either at low-medium b values (FB acquisitions: 50-100-150-300 s/mm 2 ) or medium-high b values (BH acquisitions: 300-1000 s/mm 2 ). This finding is unexpected since in the normal liver, aging does not imply a fibrotic/cirrhotic-like evolution [33], but it is well known that there is about a 40% reduction in blood flow and a similar or slightly less reduction in liver mass [33][34][35][36][37][38][39]. The reasons for this age-linked reduction in hepatic blood flow and volume, which are perhaps related, are still unknown but perplexing since there seem to be few significant structural or biochemical changes in the aging liver [40][41][42].…”