Pharmacokinetics and therapeutic drug monitoring of gentamicin in the elderly

Gentamicin is frequently used in elderly patients as serious infection, par ticularly Gram-negative bacilli, remains one of the major health problems e xperienced by this age group. A number of physiological changes in drug dis position occur with ageing and potentially these can affect gentamicin phar macokinetics. In particular, there is a measurable decline in renal functio n, especially after the aged of 65. Any differences in drug distribution wi th age are apparently not reflected in gentamicin disposition data, as pati ents of varying ages have similar volumes of distribution. Seriously ill patients with infections frequently require treatment with ma ny different drugs. Of note, the combination of gentamicin and a beta-lacta m antibacterial can result in inactivation. However, there appears to be no published data describing detrimental or beneficial pharmacokinetic intera ctions between gentamicin and drugs used in the elderly. Nonetheless, genta micin should be used cautiously in order to prevent potential exacerbation of its nephrotoxicity and/or ototoxicity. Such problems may occur as a resu lt of coadministration with, for example, amphotericin, cisplatin, vancomyc in, foscarnet, nonsteroidal antiinflammatory drugs or furosemide (frusemide ). The presence of concurrent disease in aged patients (e.g. malignancy, fl uid balance disorders and sepsis) may cause problems. In sepsis, for exampl e, the volume of distribution of gentamicin may be increased; however, othe r pharmacokinetic data are contradictory and inconclusive. Like other aminoglycosides, gentamicin has a narrow therapeutic index and t herapeutic drug monitoring has proven to be beneficial, particularly in vul nerable populations such as the elderly. Moreover, there is substantial pha rmacokinetic variability in these patients. Recent data support the use of extended interval or once daily doses of gentamicin. It has been suggested that because of a lack of studies for this regimen in the elderly, specific recommendations cannot yet be made. We would argue that some recommendatio ns for its cautious adoption in aged patients could be justified. Suggested procedures for the once daily administration of gentamicin include the use of the 'Hartford' nomogram and the targeted area under the concentration-t ime curve. The susceptibility of the elderly to aminoglycoside-related nephrotoxicity (and probably ototoxicity) may arise from a decline in renal function and a n impaired capacity for cellular repair and regeneration. However, of great er importance is the duration of aminoglycoside therapy and the concomitant use of other nephrotoxic drugs. Further confirmation of the utility and tolerability of the once daily regi men and other possible approaches to gentamicin therapy in the elderly are essential.