Aminoglycosides elimination rates

The elimination rate constant (kc) of the aminoglycoside in this patient was approximately... 

Upon the administration of 1 gram of an aminoglycoside every 12 hours, the Cmj v, was found to be 8 mcg/mL. The plasma concentration at time zero was 63 mcg/mL and elimination rate constant was 0.14 hour 1. If it is desired to increase the Cmin ss to 10 mcg/mL, what should be the dose of the drug, and the new Cmax ss Assume that the drug follows linear kinetics. 

Example. Kanamycin is a member of the aminoglycoside class of antibiotics, all of which are eliminated exclusively by glomerular filtration. Creatinine is a natural body substance that is cleared almost exclusively by glomerular filtration, and creatinine clearance rate is frequently used as a diagnostic tool to determine glomerular filtration rate. The relationship... 

Underlying disease states that may affect antibiotic metabolism and/or elimination should be considered when developing a prophylactic regimen. For example, patients with thermal burn and spinal cord injuries eliminate certain classes of antibiotics, primarily the aminoglycosides and /3-lactams, at unusually high rates compared with controls. Individuals undergoing cardiac bypass may have altered antibiotic disposition related to increased volume of distribution and reduced total-body clearance and thus require special dosing consideration. ... 

Mezlocillin is effective in combination with an aminoglycoside in the treatment of life-threatening infections caused by P. aeruginosa. In the treatment of febrile episodes in immunosuppressed patients with granulocytopenia, it may be combined with an aminoglycoside or a cephalosporin. The rate of elimination of mezlocillin is dose-dependent and related to the degree of renal function impairment. Dosage adjustments are not required in patients with mild impairment of renal function. 

Is it possible for the rate constant associated with elimination to have a greater value than that for the distribution rate constant The answer to this is "Yes." This type of flip-flop kinetics occurs for the aminoglycoside antibiotic gentamicin. In the case of gentamicin, the terminal (fi) portion of the curve, which represents the slower process, corresponds to distribution while the steep feathered line, whose slope is -a/2.303, corresponds to the faster process (the elimination process in this case). Ordinarily, for most drugs, this is not the case, and we can refer to a as the distribution rate constant and to jS as the postdistribution rate constant. 

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