These polar drugs do not penetrate into most cells, central nervous system (CNS), and the eye. Except for streptomycin, there is negligible binding of aminoglycosides to plasma proteins. The volume of distribution of these drugs approximates the volume of extracellular fluid.

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.

Aminoglycoside concentrations in CSF following parenteral administration are <10% of those in plasma (~25% with meningitis). Thus, CSF levels are usually subtherapeutic unless delivered intrathecally. Similarly, effective therapy of bacterial endophthalmitis requires periocular and intraocular injections.

Administration of aminoglycosides to pregnant women may result in drug accumulation in fetal plasma and amniotic fluid. Streptomycin and tobramycin can cause hearing loss in children born to women who receive the drug during pregnancy. Aminoglycosides should be used with caution during pregnancy and only in the absence of suitable alternatives.

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