Half-life aminoglycosides

A novel approach to the modification of aminoglycoside pharmacokinetics is under investigation (84). Administration of gentamicin encapsulated in egg phosphatidylcholine Hposomes has been found to lead to a longer half-life and much higher spleen and Hver levels for the gentamicin component. This formulation is undergoing clinical study (85). 

Routine use of once-daily aminoglycosides in CF is not recommended and should be limited to adults and older teens, in whom the time below the MIC can be minimized. Due to a shorter half-life, once-daily aminoglycoside dosing does not appear to be optimal for use in younger children. 

The elimination half-life (t1/2) of the aminoglycoside in this patient was approximately... 

At 2 h after dosing, the plasma concentration was 4.6 mg/mL at 5 h, the concentration was 2.4 mg/mL. Therefore, the plasma concentration of this aminoglycoside decreased to one-half in approximately 3 h—its half-life. In addition, drug elimination usually occurs according to first-order kinetics (i.e., a linear relationship is obtained when the drug concentration is plotted on a logarithmic scale vs. time on an arithmetic scale (a semilogarithmic plot)]. 

Upon the administration of 0.5 g of an aminoglycoside every 12 hours, the Cmin ss was found to be 8 mcg/mL, the plasma concentration at time zero was 36 mcg/mL, and elimination half-life was 5 hour"1. If it is desired to increase the Cmin ss to 10 mcg/mL, what should be the dose of the drag, and the new Cmax ss Assume that the drug follows linear kinetics. 

Various Pharmacokinetic Parameters of the Aminoglycosides Aminoglycoside Half-life (h)... 

Toxicity Aminoglycosides are associated with significant nephrotoxicity or ototoxicity. These agents are excreted primarily by glomerular filtration thus, the serum half-life will be prolonged and significant accumulation will occur in patients with impaired renal function. Toxicity may develop even with conventional doses, particularly in prerenal azotemia or impaired renal function. 

Mechanism of Action An aminoglycoside antibacterial that binds to bacterial microorganisms. Therapeutic Effect Interferes with bacterial protein synthesis. Pharmacokinetics Poorly absorbed from the GI tract following PO administration. Protein binding Low. Primarily eliminated unchanged in the feces minimal excretion in urine. Removed by hemodialysis. Half-life 3 hr. 

The normal half-life of aminoglycosides in serum is 2-3 hours, increasing to 24-48 hours in patients with significant impairment of renal function. Aminoglycosides are only partially and irregularly removed by hemodialysis—eg, 40-60% for gentamicin—and even less effectively by peritoneal dialysis. 

Renal failure will result in a diminished elimination of drugs that are primarily secreted, such as penicillins and aminoglycosides, and therefore in a longer half-life of the drug (45). Likewise, liver disease may result in a capacity-limited biotransformation, and consequently in a slower elimination of the drug. Bacterial pneumonia in calves may also result in increased serum oxytetracycline concentrations, a condition that can cause prolonged elimination (46). 

The thermal stability of oxytetracycline in liquid media, as indexed by the antimicrobial activity retained following heating at 71 C, has been shown to be much less than that of other antibiotics such as aminoglycosides and -lactams (71, 72). Recent investigation on the thermostability of oxytetracycline in water and vegetable oil showed that the drug is unstable in water at 100 C with a half-life of 2 min, but more stable in oil at 180 C with a half-life of 8 min. 

Schreier et al. [85] examined the effects of liposome encapsulation on the pharmacokinetics in sheep of amikacin, a water-soluble aminoglycoside. The dmg was formulated in 200 nm liposomes and administered by means of intratracheal instillation. The liposome formulations were soy PC/phosphatidyl glycerol (PG) (7 3 molar ratio) and soy PC/PG/CH (4 3 3). They found that both liposome formulations reduced plasma Cmax and prolonged the plasma half-life of the amikacin compared with the dmg administered as a solution, once again indicating that liposomes were controlling dmg delivery in the lungs. The inclusion of cholesterol in liposomes more than tripled the plasma half-life for the dmg compared with the liposomes without cholesterol. Cholesterol reduces the fluidity and permeability of liposomes in their liquid crystalline phase. 

Amphotericin prolongs the half-life of aminoglycoside antibiotics (147). 

Aminoglycosides are almost exclusively eliminated by glomerular filtration. Elimination is dependent on cardiovascular and renal function, age, fever, other physiological factors and the V. The half-lives are usuaUy 1-2 h in normal adult horses but are increased in horses with renal dysfunction and in neonates. Increased dosage intervals must be used in these patients to prevent nephrotoxicity. The renal elimination of the aminoglycosides increases with age. The half-life of gentamicin is approximately 50% longer in 1-day-old than in 30-day-old foals. 

Indications Neuromuscular blockade, endotracheal intubation Category Non-depolarizing neuromuscular blocker Half-life initial 2 minutes terminal 20 minutes Clinically important, potentially hazardous interactions with amikacin, aminoglycosides, anesthetics, antibiotics, gentamicin, halothane, kanamycin, neomycin, piperacillin, streptomycin, tobramycin... 

Indications Various infections caused by susceptible organisms Category Antibiotic, aminoglycoside Half-life 2-4 hours... 

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