Author(s): Segal JL, Brunnemann SR, Gordon SK, Eltorai IM
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Abstract The influence of chronic (greater than 1 yr duration) spinal cord injury (SCI) on the disposition of amikacin was studied in seven healthy subjects with SCI (five paraplegic, two tetraplegic) and seven able-bodied controls (intact neuraxes). The time course of amikacin serum concentration after a 30-minute infusion (7.5 mg/kg) was followed for up to 8.5 hours using fluorescence polarization immunoassay. Pharmacokinetic values were estimated by a noncompartmental analysis (NC). Amikacin steady-state volume of distribution (Vss) was increased to 0.20 +/- 0.04 l/kg (mean +/- SD) as compared to 0.17 +/- 0.02 l/kg in able-bodied controls (p 0.03), and its mean terminal elimination half-life in patients with SCI was prolonged by 0.64 hours over the control value of 2.11 +/- 0.27 hours (p 0.01). The NC estimated mean residence time (MRT) in patients with SCI (3.65 +/- 0.75 hrs) was 0.89 hours longer than that observed in controls (p 0.03). Our data suggest that the Vss, half-life, and MRT of amikacin are increased in persons with chronic SCI. As a result, amikacin dosing regimens developed in able-bodied humans may demonstrate diminished efficacy when extrapolated uncritically to these patients.
This article was published in Pharmacotherapy
and referenced in Journal of Drug Metabolism & Toxicology