Aminoglycosides Subject

The intravenous curve is, by definition, a representation of 100% bioavailability as the drug was put in its entirety into the vein. The oral curve has an area under it approximately 75% the size of the intravenous curve, and this suggests that 25% of the oral dose failed to get into the circulation. The oral bioavailability of the drug is the proportion getting into the vascular compartment, and can be measured if there is an intravenous dose curve available for the same subject at the same dose. In this example, F (the fraction bioavailable) is 0.75. It might be as high as 1.0 (100%) for some steroids, or as low as 0.1 (10%) or even less for poorly absorbed aminoglycosides. 

Of the effective compodnds available at the present time, the )3-lactam antibiotics, the aminoglycosides and the polymyxins are all bacteriocidal. The j8-lactam antibiotics, notably carbenicillin, suffer primarily from the penetration factor but enzyme activity can play an important part. The aminoglycosides, on the other hand, have few or no penetration problems but are subject to enzymatic modification. The polymyxins penetrate to the active site and appear to be resistant to enzymatic modification. However, toxicity problems associated with polymyxin therapy prevent the widespread use of these drugs. 

With aminoglycosides, systemic therapy is associated with a risk of ototoxicity and nephrotoxicity. However, no toxicity has been reported in several well-controlled trials of inhaled tobramycin in which subjects received repetitive courses [31,32]. 

The 3"-A-acetylation of arbekacin 260 and amikacin 2, the first example of 3"-A-acetylation of aminoglycoside antibiotics by enzymatic modification, was reported in 1988. Subjection of kanamycin group antibiotics to an aminoglycoside 3-A-ace-... 

Because of their polar nature, the distribution of aminoglycosides is largely restricted to the extracellular space. Consequently, their distribution volume is small both in animals and humans. It equals the volume of the extracellular space or approximately 0.25 L/kg body weight, in normal subjects. 

Aminoglycosidic antibioties inhibit protein synthesis on bacterial ribosomes, but the primary sites that are subject to the action of each of these antibiotics are different and are now under study. As yet, there is no information about the chemical structure of the primary sites, and... 

An ion cyclotron resonance study of ion-molecule reactions in benzene has shown that the cyclopropenyl cation arises from a a-type complex between protonated benzene and benzene. The mass spectral fragmentation of cyclopropanol monoethers has been examined and subjected to theoretical study and the fragmentation of a series of underivatized aminocyclitol-aminoglycoside antibiotics is believed to involve the ion (387). The chemical ionization mass spectrum of oct-6-en-3-one has been interpreted as involving the cyclobutyl-cyclopropylcarbinyl cation rearrangement (388)- (389). ... 

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