title: Effect of age on pharmacokinetics and pharmacodynamics in man.
abstract: Elderly patients represent an increasing part of our population who consume disproportionately high amounts of drugs. During aging physiological and disease-induced changes occur which might affect PK and/or PD of many drugs. The calcium channel blocker verapamil and the benzodiazepine midazolam were taken as examples to illustrate some problems and open questions in research pertaining to the elderly. Following an acute i.v. dose of racemic verapamil and during steady-state (120 mg bid p.o.) no significant differences of the stereoselective disposition of S- and R-verapamil could be found between younger and older healthy subjects. Concomitant intake of rifampicin (600 mg/die) induced especially the presystemic (prehepatic) metabolism of verapamil so that oral bioavailability approached zero and PD effects almost diminished. Intestinal metabolism and inducibility were well preserved in the elderly. The PK and PD of midazolam were investigated in young and older patients who received an i.v. bolus of 0.05 and 0.03 mg/kg, respectively, for premedication prior to third molar teeth extraction. Again, no significant differences in the PK parameters were found between both groups. However, the sedative effects were much more pronounced in the elderly and this population demonstrated a significantly higher CNS-sensitivity to midazolam. All physicians should be aware that for various reasons drug response can be age-dependent and therefore more PK-PD data are needed for the elderly.
authors.affiliation: Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Klotz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D014151:Anti-Anxiety Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D019540:Area Under Curve; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D006801:Humans; D007275:Injections, Intravenous; D008874:Midazolam / Q000493:pharmacokinetics* / Q000494:pharmacology; D008875:Middle Aged; D014700:Verapamil / Q000493:pharmacokinetics* / Q000494:pharmacology
chemical_list: D014151:Anti-Anxiety Agents; D002121:Calcium Channel Blockers; D014700:Verapamil; D008874:Midazolam