KINETICS OF GENTAMICIN AFTER INTRAVENOUS, INTRAMUSCULAR, AND INTRA-TRACHEAL ADMINISTRATION IN SHEEP

  • 1 January 1981
    • journal article
    • research article
    • Vol. 42  (11) , 1901-1904
Abstract
Kinetics of gentamicin (2.2 mg/kg of body wt) were investigated in 7 sheep after i.v. bolus administration. The mean serum concentration profile could be described by a 2-compartment open model with a distribution rate constant (.alpha.) of 3.112 .+-. 1.681 h-1 [half-life, t1/2(.alpha.) = 17.22 .+-. 8.63 min] and an overall elimination rate constant (.beta.) of 0.485 .+-. 0.028 h-1 [t1/2(.beta.) = 85.87 .+-. 5.03 min]. The apparent volume of distribution was somewhat restricted [Vd(area) = 0.194 .+-. 0.059 l/kg] and the total body clearance was 1.559 .+-. 0.400 ml/kg per min. Equal dosages of gentamicin (2.2 mg/kg) were also given i.m. and intratracheally (i.t.). After i.m. injection, gentamicin reached peak serum concentration at postinjection minutes (PIM) 45, surpassing concentrations after the i.v. injection for the remainder of the experiment. The i.t. injection produced detectable serum concentrations at PIM 5, with a peak concentration at PIM 60. The serum drug concentrations after i.t. injections remained well below concentrations after i.v. and i.m. injections. Radiographic analysis of an i.t. injection of a gentamicin-tantalum suspension revealed good distribution throughout the trachea and proximal bronchi, with physical clearance of the tantalum occurring after .gtoreq. 10 min. Aspiration biopsy of a tracheal wash 6 h after i.t. gentamicin injection revealed no cytologic response to gentamicin in 6 of 7 sheep, with the single response that of a purulent exudate.

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