Pharmacokinetics and therapeutic drug monitoring of gentamicin in the elderly

Gentamicin is frequently used in elderly patients as serious infection, particularly Gram-negative bacilli, remains one of the major health problems experienced by this age group. A number of physiological changes in drug disposition occur with ageing and potentially these can affect gentamicin pharmacokinetics. In particular, there is a measurable decline in renal function, especially after the aged of 65. Any differences in drug distribution with age are apparently not reflected in gentamicin disposition data, as patients of varying ages have similar volumes of distribution. Seriously ill patients with infections frequently require treatment with many different drugs. Of note, the combination of gentamicin and a beta-lactam antibacterial can result in inactivation. However, there appears to be no published data describing detrimental or beneficial pharmacokinetic interactions between gentamicin and drugs used in the elderly. Nonetheless, gentamicin should be used cautiously in order to prevent potential exacerbation of its nephrotoxicity and/or ototoxicity. Such problems may occur as a result of coadministration with, for example, amphotericin, cisplatin, vancomycin, foscarnet, nonsteroidal antiinflammatory drugs or furosemide (frusemide). The presence of concurrent disease in aged patients (e.g. malignancy, fluid balance disorders and sepsis) may cause problems. In sepsis, for example, the volume of distribution of gentamicin may be increased; however, other pharmacokinetic data are contradictory and inconclusive. Like other aminoglycosides, gentamicin has a narrow therapeutic index and therapeutic drug monitoring has proven to be beneficial, particularly in vulnerable populations such as the elderly. Moreover, there is substantial pharmacokinetic 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 recommendations 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-time curve. The susceptibility of the elderly to aminoglycoside-related nephrotoxicity (and probably ototoxicity) may arise from a decline in renal function and an impaired capacity for cellular repair and regeneration. However, of greater 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 regimen and other possible approaches to gentamicin therapy in the elderly are essential.