Aminoglycosides pharmacokinetics

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). 

Epidemiology of aminoglycoside nephrotoxicity Risk factors for aminoglycoside nephrotoxicity Aminoglycoside pharmacokinetics Renal transport of aminoglycosides... 

Jorgenson, J.A. Rewers, R.F. Justification and evaluation of an aminoglycoside pharmacokinetic dosing service. 

In hospitals with a significant pharmacy influence on antimicrobial therapy, it may be impossible for the infectious diseases pharmacist to perform all the functions described here. Instead, the pharmacist may need to delegate the responsibility for conducting standardized antimicrobial protocols (therapeutic interchange, intravenous to oral, aminoglycoside pharmacokinetics) to other pharmacists, while maintaining accountability for the quality of these programs. 

Bauer LA, Edwards WAD, Dellinger EP, Simonowitz DA. Influence of weight on aminoglycoside pharmacokinetics in normal weight and morbidly obese patients. Eur J Clin Pharmacol 1983 24 643-647. 

Papich and Riviere report marked variability in aminoglycoside pharmacokinetics (distribution, clearance, and half-life) with altered physiologic or pathologic states, including pregnancy, obesity, dehydration, immaturity, sepsis, endotoxemia, and renal disease. The latter influence is predictable from the fact that body clearance is dependent almost entirely on renal excretion. Martin-Jimenez and Riviere concluded that aminoglycoside pharmacokinetics can be predicted across species by population pharmacokinetic modeling. ... 

Czock D, Giehl M, Keller F (2000) A concept for pharmacokinetic-pharmacodynamic dosage adjustment in renal impairment the case of aminoglycosides. Clin Pharmacokinet 38(4) 367—375. Erratum in Clin Pharma-cokinet 2000 39(3) 231... 

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. 

Obtain serum drug levels for aminoglycosides and/or vancomycin and perform pharmacokinetic analysis. Adjust the dose, if needed, according to the parameters in Table 13-2. Obtain follow-up trough levels at weekly intervals or sooner if renal function is unstable. Follow serum creatinine levels if renal function is unstable. Hearing tests may be scheduled yearly or per patient preference. 

Integration of both pharmacokinetic and pharmacodynamic properties of an agent is important when choosing antimicrobial therapy to ensure efficacy and prevent resistance. Antibiotics may demonstrate concentration-dependent (aminoglycosides and fluoroquinolones) or time-depen-dent (/l-1 acta ms) bactericidal effects. 

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

Burn patients In patients with extensive burns, altered pharmacokinetics may result in reduced serum concentrations of aminoglycosides. 

Pharmacokinetics Oral aminoglycosides are poorly absorbed therefore, use only for suppression of Gl bacterial flora. 

The pharmacokinetic behavior of the aminoglycosides is characterized by poor oral absorption. 

TTie major clinically important aminoglycosides are amikacin (Amikin), gentamicin Garamycin), kanamycin (Kantrex), netilmicin Netromycin), neomycin Myci-fradin), streptomycin, and tobramycin (Nebcin). Their pharmacokinetic characteristics are shown in Table 46.1. 

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. 

Van Lent-Evers, N.A., Mathot, R.A., Geus, W.P., van Hour, B.A., and Vinks, A.A. (1999) Impact of goal-oriented and model-based clinical pharmacokinetic dosing of aminoglycosides on clinical outcome a cost-effectiveness analysis. Ther Drug Monit 21 63-73. 

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. 

Nagai J, Takano M. Molecular aspects of renal handling of aminoglycosides and strategies for preventing the nephrotoxicity. Drug Metab Pharmacokinet. 2004 19 159-170. 

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. 

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. 

Morike K, Schwab M, Klotz LJ. Use of aminoglycosides in elderly patients Pharmacokinetic and clinical considerations. Drugs Aging 1997 10 259-77. 

In the purposeful search that followed the demonstration of the clinical efficacy of penicillin, streptomycin was obtained from Streptomyces griseus in 1944, cultured from a heavily manured field, and also from a chicken s throat. Aminoglycosides resemble each other in their mode of action, and their pharmacokinetic, therapeutic and toxic properties. The main differences in usage reflect variation in their range of antibacterial activity crossresistance is variable. 

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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