Aminoglycosides distribution

Some drugs such as digoxin and lithium take several hours to distribute to tissues. Digoxin samples should be taken at least 6 hours after the last dose and lithium just before the next dose (usually 24 hours after the last dose). Aminoglycosides distribute quite rapidly, but it is still prudent to wait 1 hour after giving the dose before taking a sample. 

Whelton A. Renal tubular transport and intrarenal aminoglycoside distribution. In Whelton A, Neu HC, editors. The Aminoglycosides. New York, Basel Marcel Dekker, 1982 191. 

Although most CF patients have shorter half-lives and larger volumes of distribution than non-CF patients, some patients exhibit decreased clearance. Possible causes include concomitant use of nephrotoxic medications, presence of diabetic nephropathy, history of transplantation (with immunosuppressant use and/or procedural hypoxic injury), and age-related decline in renal function in older adult patients. Additionally, CF patients are repeatedly exposed to multiple courses of IV aminoglycosides, which can result in decreased renal function. Evaluation of previous pharmacokinetic parameters and trends, along with incorporation of new health information, is key to providing appropriate dosage recommendations. 

Accelerated drug elimination is also a possible reason for failure and may occur in patients with cystic fibrosis or during pregnancy, when more rapid clearance or larger volumes of distribution may result in low serum concentrations, particularly for aminoglycosides. 

Also on the nucleic acid field, it has been shown95 that the distribution pattern of NH2/NH3 + /OH groups in natural aminoglycosides could indirectly influence their RNA binding properties and therefore their antibiotic functions. Indeed, the number and location of these polar groups is essential to modulate the conformation and dynamics of the glycoside with the concomitant implication for the RNA recognition process. 

Diuretics which reduce plasma volume may lead to increased Cp of drugs distributed mainly to the plasma compartment such as aminoglycosides. 

In contrast, the volume of distribution of water-soluble compounds to reach a target plasma concentration is decreased. Likewise, due to the decreased volume of distribution, the loading dose of aminoglycosides is less in older patients. 

Aminoglycosides are most useful for bacteraemias (especially Gram-negative septicaemia) since their volume of distribution is relatively low. With the exception of patients with renal failure or endocarditis they should be administered once-daily. This is because they exhibit a dose-dependent pharmacodynamic effect. This means that bactericidal activity is determined more by the peak plasma concentration than by the time that the plasma concentration is above the minimum required to achieve bacterial killing. The converse is true of p-lactams, which exhibit t/me-cfepenofent bacterial killing. 

Aminoglycosides are absorbed very poorly from the intact gastrointestinal tract almost the entire oral dose is excreted in feces after oral administration. However, the drugs may be absorbed if ulcerations are present. After intramuscular injection, aminoglycosides are well absorbed, giving peak concentrations in blood within 30-90 minutes. Aminoglycosides are usually administered intravenously as a 30- to 60-minute infusion after a brief distribution phase, this results in serum concentrations that are identical with those following intramuscular injection. 

Aminoglycosides have a low volume of distribution and are excreted by glomerular filtration, which is followed by active reuptake via a high-capacity, low-affinity transport system. The aminoglycosides remain in the kidney longer than in other exposed tissues such as the liver. Thus, with gentamycin, the time for the tissue concentration to be reduced by half is... 

Pharmacokinetics. The aminoglycosides are not reliably absorbed following oral dosing, so they are administered primarily by intravenous infusion or intramuscular injection. Distribution throughout the vascular and interstitial space is fairly rapid, but intracellular, cerebrospinal fluid, and bronchial secretion levels are generally low. Most of the administered dose is eliminated unmetabolized in the urine. 

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. 

Table 7.19. DISTRIBUTION OF GENTAMICIN AND BB-K8 MIC VALUES FOR PSEUDOMONAS STRAINS FOUND RESISTANT TO ONE OR BOTH AMINOGLYCOSIDES [111]...

Pharmacokinetics. Aminoglycosides are water-soluble and do not readily cross cell membranes. Poor absorption from the intestine necessitates their administration i.v. or i.m. for systemic use and they distribute mainly to the extracellular fluid transfer into the cerebrospinal fluid is poor even when the meninges are inflamed. Their t) is 2-5 h. 

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