Gentamicin Bioavailability and Single-Dose Pharmacokinetics in Spinal Cord Injury

Abstract

The rate and completeness of absorption of gentamicin from muscle (healthy and paralyzed) and gentamicin disposition kinetics following a single intravenous infusion were studied in nonobese, healthy male volunteers with functionally complete, chronic (greater than one year duration) spinal cord injury (SCI) and in able-bodied controls. Pharmacokinetic parameters were derived using compartmental and model-independent analyses. The absolute bioavailability of gentamicin was complete and did not differ from control values using both model-independent (LAGRAN) and model-dependent (ADAPT) analyses. The rate of gentamicin absorption in patients with SCI was, however, significantly slower, with a mean absorption time of 2.55 h compared with 0.96 h in able-bodied controls (p ≤ 0.05). Mean volume of distribution steady-state (V_d^ss) of gentamicin was demonstrated to be 33–47 percent greater in spinal cord injury than in controls (p < 0.05). We conclude that the absorption of gentamicin from paralyzed muscle is significantly impaired, and in conjunction with an increase in V_d^ss results in delayed, decreased peak serum levels in patients with SCI.