The blood plasma drug concentrations achieved during multiple daily dose therapy with aminoglycosides usually correlates with clinical outcome in patients with bacteremia and in patients with pneumonia. Raising the aminoglycoside plasma concentration to its in vitro minimum inhibitory concentration against the isolated pathogen is a useful indicator of the adequacy of amino-glycoside dosing.

Both the rate and extent of gastrointestinal absorption of individual aminoglycosides are generally quite low. For example, more than 95% of an oral dose of neomycin is excreted unchanged in the feces. The systemic bioavailability of the aminoglycosides is low across other membranes as well. For example, gentam-icin is poorly absorbed from a topical ophthalmic preparation, and there is little systemic absorption of either inhaled tobramycin or aminoglycosides instilled into the urinary bladder. Neomycin bioavailability across intact skin is also low, although absorption across damaged skin can be significant: nephrotoxicity can occur in burn patients treated with topical neomycin.

Because of their aqueous solubility and modest binding to plasma and tissue proteins, the distribution of the aminoglycosides corresponds to that of the extracellular fluid. Four compartments can be distinguished. The central compartment corresponds to the intravas-cular space; the rapidly equilibrating compartment corresponds to the extracellular visceral space; the slowly equilibrating compartment largely corresponds to that of skeletal muscle; and the extremely slowly equilibrating compartment presumably corresponds to that of bone, proximal renal tubules, otolymph, and other tissue where binding to phospholipids or mineral matrix occurs. Gentamicin fails to reach intraocular fluid or cere-brospinal fluid in significant concentrations after intravenous injection, although it may reach bactericidal levels in cerebrospinal fluid in patients with meningeal inflammation, such as occurs in meningitis. However, direct intrathecal injection of gentamicin may still be required for reliable bactericidal levels.

Most of the enzymes that catalyze the metabolism of foreign compounds are found inside cells. As aminoglycosides do not penetrate most cells, they do not undergo any significant metabolism. Nearly all of an intravenous dose is cleared by the kidneys and can be recovered in the urine. Aminoglycoside clearance is approximately equal to that of the glomerular filtration rate, resulting in fairly high urine concentrations; the latter contributes to the efficacy of the aminoglycosides in urinary tract infections.

Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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