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Pharmacotherapy: Pharmacokinetics and Pharmacodynamics (including: ADE, TDM, DUE)
Are the official recommendations for amikacine serum levels suitable for older patients?
  1. A. Lajoinie,
  2. B. Leroy,
  3. M. Duquaire,
  4. C. Gregoire,
  5. A. Blot,
  6. P. Maire,
  7. M. Ducher,
  8. L. Bourguignon
  1. 1Hopital Antoine Charial HCL, Pharmacy, Francheville, France

Abstract

Background The aminoglycosides represent the mainstay in the treatment of serious Gram-negative infections. Their use is difficult in older patients because of high potential toxicity and the large observed inter-individual variability. In recent years, higher peak serum concentrations have been suggested in official recommendations for amikacin treatment (peak level: 60 to 80 μg/ml, trough level: < 2.5 μg/ml). The applicability of these target concentrations is questionable in geriatric patients.

Purpose Our objective was to check the applicability of those target levels in older patients.

Materials and methods A retrospective study was undertaken with the medical files of all patients who were treated with amikacin during the last 3 years. Anthropometric data (age, weight, creatininemia) and history of amikacin administrations and serum levels were used to estimate individual pharmacokinetic parameters with a Bayesian software program (USC*Pack). The dosage regimen needed to reach a peak level of 60 µg/ml and a trough of 2.5 µg/ml was calculated. When a dose interval of more than 48 h was needed, a complementary calculation was done to estimate trough concentration after a week of treatment with infusions every two days.

Results Twenty-eight patients were considered, with a male/female ratio of 13/15, age 83±8 years, weight 64.2±3.7 kg and estimated creatinine clearance 55±21 ml/min. Mean estimated pharmacokinetic parameters were respectively: volume of distribution of 0.31±0.11 l/kg and amikacin clearance of 45.2±36.1 ml/min. Ideal dose interval was above 48 h for 12 patients (43%) with a mean dose interval of 62.5 h. For these patients, trough serum concentration level after a week of treatment, with infusions every two days, was 7.72±5.88 μg/ml.

Conclusions This study shows that for more than 40% of older patients, the target peak cannot be reached without potentially toxic trough levels even after 48 h, or without expanding the dose interval above. Such a wide dose interval can risk inefficacy for serious infections.

For a large number of older patients, actual amikacin target serum concentrations should be used with caution to avoid potential toxicity.

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