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  • Title: [Pharmacokinetics and nephrotoxicity of aminoglycoside antibiotics].
    Author: Marino A, Pisanti N.
    Journal: Clin Ter; 1989 Jun 30; 129(6):421-8. PubMed ID: 2526703.
    Abstract:
    Aminoglycoside antibiotics are characterized by a quick fall of blood levels (half-life 2-3 hours) and by a very slow urinary excretion (they can be detected in the urine up to 10-20 days after therapy is discontinued). This peculiar pharmacokinetic feature of these antibiotics may be attributed to some rapid steps of their pharmacokinetics (glomerular filtration, tubular reabsorption or uptake, storage in the renal cells) followed by a very slow step (transfer from these cells to tubular lumen with following urinary excretion). The aminoglycosides are very polar compounds and their uptake by tubular cells is mediated by an active transport. The uptake is responsible for the storage in the corticorenal cells. It is generally held that the storage, because of its long duration, is responsible for the nephrotoxicity, although the correlation between storage and nephrotoxicity is denied by some authors. Some practical implications of aminoglycoside pharmacokinetics could be: a) Kidney damage by aminoglycosides is often reversible, but the potential risk of nephrotoxicity must be considered to be still present at the time of the interruption of therapy. Therefore the measures during aminoglycoside therapy (prophylaxis of risk factors, monitoring of renal function, etc.) are to be continued also in the period immediately after the interruption of therapy. b) In animals some factors (high-calcium diet, calcium blockers, ACE inhibitors) are able to reduce aminoglycoside nephrotoxicity; some of them are operating through inhibition of uptake. It would be desirable to test the possible ability of these factors to reduce aminoglycoside nephrotoxicity in humans.
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