Cortex aminoglycosides

Although a number of chromatographic methods have been reported for determinations of aminoglycoside antibiotics in blood serum and urine, the application of chromatographic methods to residue analysis has been very limited. Shaikh et al (93) recently described an HPLC method for neomycin in animal tissue, and Lachatre et al (94) described a method for nine aminoglycosides in plasma, urine, and renal cortex tissue. Both procedures use post column derivatization with a-pthalaldehyde and fluorescence detection. 

Distribution All of the aminoglycosides have similar pharmacokinetic properties. Levels achieved in most tissues are low, and penetration into most body fluids is variable. Concentrations in cerebrospinal fluid are inadequate even when the meninges are inflamed. Except for neomycin, the aminoglycosides may be administered intrathecally. High concentrations accumulate in the renal cortex and in the endolymph and perilymph of the inner ear, which may account for their nephrotoxic and ototoxic potential. All cross the placental barrier and may accumulate in fetal plasma and amniotic fluid. 

The uptake of aminoglycosides into proximal renal tubular epithelial cells is limited to the luminal cell border and is saturable. Less frequent administration of doses larger than needed for saturation of this uptake may therefore reduce drug accumulation in the renal cortex (98). In vitro and in vivo data have provided evidence that partially reduced oxygen metabolites (superoxide anion, hydrogen peroxide, and hydroxyl radical), which are generated by renal cortical mitochondria, are important mediators of aminoglycoside-induced acute renal insufficiency (99). 

Kaloyanides GJ. Aminoglycoside-induced functional and biochemical defects in the renal cortex. Eundam AppI Toxicol 1984 4 930-942. 

JosepovltzC, PastorzIa-MunozE,Timmerman D, Scott M, Feldman S, Kaloyanides GJ, Inhibition ofgentamicin uptake In rat renal cortex/ n vivo by aminoglycosides and organic polycations, J Pharmacol ExpTherap, 1982,223(2) 314-21. 

Aminoglycosides Limited - mainly extracellular fluid (selective binding to renal cortex inner ear) E(r)... 

Luft FC, Kleit SA. Renal parenchymal accumulation of aminoglycoside antibiotics in rats. J Infect Dis 1974 130 656-659. Fabre J, Rudhardt M, Blanchard P, Regamey C. Persistence of sisomicin and gentamicin in renal cortex and medulla compared with other organs and serum of rats. Kidney Int 1976 10 444-449. 

Feldman S, Wang MY Kaloyanides GJ. Aminoglycosides induce a phospholipidosis in the renal cortex of the rat an early manifestation of nephrotoxicity. J Pharmacol Exp Ther 1982 220 514-520. 

Concentrations of aminoglycosides in secretions and tissues are low. High concentrations are found only in the renal cortex and the inner ear, likely contributing to the aminoglycosides nephrotoxicity and ototoxicity. Due to active hepatic secretion, concentrations in bile approach 30% of those found in plasma, but this represents a very minor excretory route. Penetration into respiratory secretions is poor. Diffusion into pleural and synovial fluid is relatively slow, but concentrations that approximate those in the plasma may be achieved after repeated administration. Inflammation increases aminoglycoside penetration into peritoneal and pericardial cavities. 

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