Aminoglycosides clinical relevance

Keeling KM, Bedwell DM (2002) Clinically relevant aminoglycosides can suppress disease-associated premature stop mutations in the IDUA and P53 cDNAs in a mammalian translation system. J Mol Med 80 367-376... 

Adverse effects from aminoglycoside are both time- and concentration-dependent. Toxicity is unlikely to occur until a certain threshold concentration is reached, but once that concentration is achieved the time beyond this threshold becomes critical. This threshold is not precisely defined, but a trough concentration above 2 mcg/mL is predictive of toxicity. At clinically relevant doses, the total time above this threshold is greater with multiple smaller doses of drug than with a single large dose. 

Aminoglycoside-induced neuromuscular blockade can be clinically relevant in patients with respiratory acidosis, in myasthenia gravis, and in other neuromuscular diseases. Severe illness, the simultaneous use of anesthetics, for example in the immediate postoperative phase, and apphcation of the antibiotic to serosal surfaces are predisposing factors (10). 

The volume of distribution of aminoglycosides is increased in young calves relative to adults, as a consequence of high extracellular water volume relative to body weight, because volume of distribution is proportional to plasma volume. Volumes of distribution are lower in obese animals, as aminoglycosides penetrate very poorly into adipose tissue. Overall, volume of distribution (Vrf,area) is of the order of 0.15-0.45 1/kg, and the clinically relevant terminal half-life (P phase) is 1.0-2.0 h. 

High doses of parenteral penicillin can inactivate aminoglycosides (245). In patients receiving low doses of aminoglycosides because of reduced renal function this can be clinically important (246,247). Parenteral administration of these drugs in neonatal dosages does not seem to produce relevant inactivation, and so temporal separation of the infusions is not required (248). 

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