Pharmacokinetics (pharmacokinetics) is best defined as the “what the body with the drug”; including absorption distribution over the body compartments metabolism excretion With aging, there are changes in these areas; some changes are clinically relevant. Metabolism and excretion of many drugs decrease, so a dose adjustment is required for some drugs. A toxic effect may develop slowly as the levels of chronic medication use over 5-6 half-lives increase until the steady state reached. For example, certain benzodiazepines (diazepam, flurazepam, chlordiazepoxide) have half-lives of up to 96 hours in the elderly; Signs of toxicity can appear until days or weeks after the commencement of treatment. Absorption Despite the age-related decrease in small bowel surface of delayed gastric emptying and the increase of the gastric pH are changes in the drug adsorption with most drugs without clinical consequence. An exception is calcium carbonate, which requires an acidic environment for optimal recording. The age-related increase in gastric pH decreased calcium absorption and increases the risk of constipation. Thus, older patients should take a calcium salt (eg. As calcium citrate) that dissolves easily in a less acidic environment. Another example of a change in absorption is the early release of enteric-coated dosage forms at elevated gastric pH. Distribution With age increases the fat content of the body generally be, and the total body water is less. The increased fat increases the volume of distribution for highly fat-soluble drugs (eg. Diazepam, chlordiazepoxide) and can increase its elimination half-life. With age, the serum albumin level decreases and the level of the ?1-acidic glycoprotein increases; However, the clinical impact of these changes on the drug binding in serum is unclear. In patients with an acute illness or malnutrition rapid decrease in serum albumin can increase the effect of drugs, as the serum levels of unbound (free) drugs may increase (only one unbound drug has a pharmacological effect). Phenytoin and warfarin are drugs with a high risk of toxic effects when the serum albumin levels decrease. Hepatic metabolism With increasing age decreases the total hepatic metabolism via the cytochrome P-450 enzyme system for most medicines. For drugs with reduced hepatic metabolism (see p. Effects of aging on metabolism * and elimination of some drugs), clearance typically reduced by 30-40%. Theoretically, the maintenance doses of medicines by this percentage should be lowered; However, the drug metabolism rate varies considerably from person to person and makes an individual dose adjustment is required. The hepatic clearance of drugs that through phase I reactions (oxidation, reduction, hydrolysis Known substances which interact with the cytochrome P-450 enzyme system in interaction) are metabolized is delayed in the elderly with a higher probability. The clearance of drugs by conjugation (phase II reactions) are metabolized is not very influenced usually by age. The first-pass metabolism (metabolism, typically hepatic, a drug before reaching the big circuit) is also affected by aging and increases by about 1% per year after age 40 from. Thus, in one orally administered dose of circulating drug levels may be higher in the elderly. Important examples of drugs with a high risk of toxic effects are nitrates, propranolol, phenobarbital and nifedipine. Renal elimination One of the key pharmacokinetic changes associated with aging is the reduced excretion of drugs through the kidneys. From the age of 30 years, creatinine clearance takes an average of 8 ml / min / 1.73 m2 / decade from; However, the age-related decline varies considerably between different people. The serum creatinine levels often remain despite a decrease in the glomerular filtration rate within the normal range, as older generally have less muscle mass and are generally less physically active than younger adults and thus produce less creatinine. Maintaining normal serum creatinine levels can be assumed that these values ??reflect the normal renal function the doctor incorrectly. Declines in tubular function with age are similar to those in glomerular function. These changes decrease renal elimination of many drugs (see p. effects of aging on metabolism * and elimination of some drugs). Clinical effects depend on the contribution of the renal elimination to total systemic elimination and of the therapeutic range of the drug (ratio of maximum tolerated dose to minimum effective dose). The creatinine clearance (measured or estimated with the aid of computer programs or a formula like the Cockcroft-Gault Formula examination of renal patients: creatinine clearance) is used as a guide for the dosage of drugs. The daily dose of drugs that are highly dependent on renal excretion should be lower, and / or frequency of dosage should be reduced. As kidney function is dynamic, adjustments to the maintenance doses of drugs may be necessary if patients become ill or are dehydrated or have only recently recovered from dehydration. Clinical Calculator: creatinine clearance (measured) Clinical Calculator: estimate the glomerular filtration rate according to the equation of the MDRD study effects of aging on metabolism * and elimination of some drugs class or category Decreased hepatic metabolism Decreased renal elimination analgesics and anti-inflammatory drugs ibuprofen meperidine, morphine naproxen meperidine (Editor’s note: not approved in Germany!) morphine oxycodone Antibiotics – amikacin, ciprofloxacin, gentamicin, levofloxacin nitrofurantoin streptomycin tobramycin cardiovascular drugs amlodipine, diltiazem, nifedipine lidocaine propranolol quinidine theophylline verapamil warfarin N-acetylprocainamide apixaban captopril dabigatran Digoxin Enalapril enoxaparin heparin procainamide lisinopril, quinapril rivaroxaban diuretics – amiloride furosemide hydrochlorothiazide triamterene Psychotropic drugs alprazolam chlordiazepoxide desipramine diazepam imipramine nortriptyline trazodone triazolam risperidone Other levodopa, amantadine chlorpropamide cimetidine exenatide gabapentin glyburide lithium metoclopramide ranitidine sitagliptin * If age-related effects on hepatic metabolism of a drug are controversial, the effects are listed that have been reported in most studies. The effect occurs in men but not in women.