Gentamicin bioavailability and single-dose pharmacokinetics in spinal cord injury.
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 less than or equal to 0.05). Mean volume of distribution steady-state (Vssd) of gentamicin was demonstrated to be 33-47 percent greater in spinal cord injury than in controls (p less than 0.05). We conclude that the absorption of gentamicin from paralyzed muscle is significantly impaired, and in conjunction with an increase in Vssd results in delayed, decreased peak serum levels in patients with SCI.
Segal
J L
JL
California College of Medicine, University of California, Irvine.
Brunnemann
S R
SR
Gray
D R
DR
D000328:Adult; D001682:Biological Availability; D005839:Gentamicins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D013119:Spinal Cord Injuries / Q000378:metabolism*; D013997:Time Factors
D005839:Gentamicins