[Calculation of the first dose of amikacine: evaluation of the current dosage recommendations].
Aminoglycosides, including amikacin, are antibiotics with major interest in the management of sepsis, but with a high potential toxicity. The French national recommendations revised in 2011 recommend a dose of amikacin ranging from 15 to 30 mg/kg. The objective was to assess if such a dose interval allows reaching the efficiency target concentrations of 64 mg/L without exceeding the toxic threshold of 2.5mg/L. From a cohort of 100 patients treated with amikacin, the individual pharmacokinetic parameters were estimated using pharmacokinetic software (MM-USCPACK). Peak and residual concentrations obtained after simulated doses ranging from 15 to 30 mg/kg were estimated and compared with the effective and toxic thresholds. The optimum dose to achieve precisely the efficiency target was calculated for each patient. Patients studied had a mean age of 79 years, mean weight of 58 kg, and mean creatinine clearance of 45 mL/min. The dose of 30 mg/kg allows the achievement of an effective peak in 98.7% of patients, but led to a potentially toxic through for 72.4% of them. The optimal dose was at mean of 1264 mg, significantly different than doses calculated with weight (P<0.0001). A weak correlation was found between weight and the optimal dose. A fixed dose of 30 mg/kg seems to be effective for most patients, but often excessive and leads to a toxic residual to 72% of patients, whereas 15 mg/kg was insufficient for most patients. The low correlation between optimal dose and patient weight shows that weight does not explain fully the interindividual variability.
Service pharmaceutique, groupement hospitalier de gériatrie, hôpital Antoine-Charial, hospices civils de Lyon, 40, avenue de la Table-de-Pierre, 69340 Francheville, France. elodie.jean-bart@chu-lyon.fr
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E
Jean-Bart
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Debeurme
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Ducher
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Bourguignon
D000368:Aged; D000369:Aged, 80 and over; D000583:Amikacin / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D001835:Body Weight / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D017408:Guidelines as Topic; D006801:Humans; D008297:Male; D012015:Reference Standards; D012984:Software
D000900:Anti-Bacterial Agents; D000583:Amikacin