Arkadiusz Gruchlik, Marcin Kochan
Pharmacokinetics of aminoglycoside antibiotics. Based on population pharmacokinetic data determination of the loading dose, maintenance dose and dosage interval
2021-03-26
Pharmacokinetics of aminoglycoside antibiotics. Based on population pharmacokinetic data determination of the loading dose, maintenance dose and dosage interval
Aminoglycosides are natural or semisynthetic antibiotics derived from actinomycetes. They bind to the bacterial ribosome, leading to inhibition of protein synthesis. The spectrum of activity, rapid bactericidal activity, and favorable chemical and pharmacokinetic properties of aminoglycosides make them a clinically useful class of drugs. As aminoglycosides exhibit concentration-dependent killing, peak concentrations (Cmax) and Cmax/MIC ratios have been postulated to be the best predictors of therapeutic efficacy. Conventional and extended interval dosing is used in the administration of these drugs. Conventional dosing refers to a weight-based dose divided two to three times daily. Extended-interval therapy also known as once-daily dosing utilizes a higher weight-based dose administered at an extended interval (every 24 hours for those with normal renal function and longer for those with renal dysfunction). The main noted adverse effects of aminoglycosides are ototoxicity, nephrotoxicity, and neuromuscular blockade. Aminoglycoside antibiotics, due to their narrow therapeutic index, numerous side effects, and high toxicity, belong to the group of drugs whose blood concentration must be monitored. Because aminoglycosides are primarily renally eliminated, the elimination constant (Kel) is directly related to the creatinine clearance (CLcr). The Cockcroft-Gault formula for estimating creatinine clearance is used to provide a reliable approximation of a residual renal function. Aminoglycosides weight-based dosing should be based on ideal, total, or adjusted body weight. In the event of renal failure, sepsis, burns, peritoneal dialysis leading to a change in the volume of distribution, the loading dose, maintenance dose and the dosing interval of aminoglycosides should be adjusted to achieve the target maximum and minimum concentrations.
This study provides practical methods how to determine these parameters, based on data such as patient weight, creatinine clearance, patient age, comorbid disease, and population pharmacokinetics.
Keywords: pharmacokinetics, therapeutic drug monitoring, aminoglycoside antibiotics.
© Farm Pol, 2021, 77 (2): 63–70