Fluctuation of the volume of distribution of amikacin and its effect on once-daily dosage and clearance in a seriously ill patient

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Abstract
The main aim of the trial was to determine the extent to which the volume of distribution of amikacin fluctuates in a seriously ill patient receiving copious quantities of i.v. fluid over an extended term of treatment. The impact of the volume fluctuation on amikacin therapeutic peak concentrations was also assessed. The case report describes a young, previously healthy male adult admitted to the surgical ICU of a teaching hospital following trauma to the head and central nervous system. The patient received 1 g of amikacin once-daily i.v. for 35 consecutive days as part of an antimicrobial regimen. Blood samples were drawn for routine amikacin concentration determinations on 14 occasions, extending over the entire term of treatment, from which the required pharmacokinetic parameters were determined. The volume of distribution of amikacin varied extensively from 0.27 to 0.61 l/kg (normal range 0.27 +/- 0.06 1/kg) notwithstanding the fact that amikacin clearance remained satisfactorily high throughout the term of treatment. Once-daily therapeutic amikacin concentrations fluctuate extensively and rapidly in the seriously ill patient receiving copious quantities of i.v. fluids, despite competent renal function. The volume expansion seen in our patient is difficult to account for in terms of the extracellular fluid compartment only. (a) Once-daily regimen amikacin peak concentrations should be frequently monitored in the seriously ill patient; (b) once-daily amikacin regimens are best monitored using blood specimens drawn at 1 and 6-8 h post administration.