Pharmacokinetics of gentamicin C-1, C-1a, and C-2 in beagles after a single intravenous dose

The pharmacokinetics of gentamicin C-1, C-2, and C-1a, were studied in six beagles after administration of gentamicin at 4 mg/kg of body weight as a s ingle intravenous bolus dose, Plasma concentrations of the gentamicin compo nents were analyzed with a novel high-performance liquid chromatography met hod capable of identifying and quantifying each of the components, The phar macokinetic analysis of the plasma concentration-versus-time data was perfo rmed using the noncompartmental approach. The results indicated significant differences in the pharmacokinetic characteristics between the gentamicin components C-1, C-1a, and C-2. The mean residence times of gentamicin C-1, C-1a, and C-2 were 81 +/- 13, 81 +/- 12, and 79 +/- 13 min (mean +/- standa rd deviation), respectively. The half-lives of the respective components we re 64 +/- 12, 66 +/- 12 and 63 +/- 12 min. Clearance (CL) of gentamicin C-1 , 4.62 +/- 0.71 ml min(-1) kg(-1), was significantly higher (P = 0.0156) th an CL of gentamicin C-1a, 1.81 +/- 0.26 ml min(-1) kg(-1), and C-2, 1.82 +/ - 0.25 ml min(-1) kg(-1). Similarly, the volume of distribution at steady s tate (V-ss) of gentamicin C-1, 0.36 +/- 0.04 liter kg(-1), was significantl y higher (P = 0.0156) than the V-ss of gentamicin C-1n, 0.14 +/- 0.01 liter kg(-1), and C-2, 0.15 +/- 0.02 liter kg(-1). Tissue binding was considered the most likely cause for the difference. The difference may have clinical and toxicological significance.