Pharmacokinetics gentamicin

Amin NB, Padhi ID, Touchette MA, Patel RV, Dunfee TP, Anandan JV. Characterization of gentamicin pharmacokinetics in patients hemodialyzed with high-flux polysulfone membranes. Am J Kidney Dis 1999 34 222-7. 

Zaske DE, Cipolle RJ, Rotschafer JC, Solem LD, Mosier NR, Strate RG. Gentamicin pharmacokinetics in 1,640 patients method for control of serum concentrations. Antimicrob Agents Chemother 1982 21(3) 407-11. 

McNamara DR, Nafziger AN, Menhinick AM, Bertino JS. Jr. A dose-ranging study of gentamicin pharmacokinetics implications for extended interval aminoglycoside therapy. J Clin Pharmacol 2001 41(4) 374-7. 

Giroux, D., Sirois, G. Martineau, G.-P. (1995) Gentamicin pharmacokinetics in newborn and 42-day-old male piglets. Journal of Veterinary Pharmacology and Therapeutics, 18, 407-412. 

Zank KE, Miwa L, Cohen JL, et al. Effect of body weight on gentamicin pharmacokinetics in neonates. Clin Pharm 1984 3 170—173. 

Haughey DB, Hilligoss DM, Grass A, et al. Two-compartment gentamicin pharmacokinetics in premature neonates A comparison to adults with decreased glomemlar filtration rates. J Pediatr 1980 96 325-330. 

Manley HJ, Bailie GR, McClaran ML, Bender WL. Gentamicin pharmacokinetics during slow daily home hemodialysis. Kidney Int 2003 63 1072-1078. 

JC Rotschafer, C Morlock, L Strand, K Crossley. Comparison of radioimmunoassay and enzyme immunoassay methods in determining gentamicin pharmacokinetic parameters and dosages. Antimicrob. Agents Chemother 22 648, 1982. 

DeanRP, DomanicoRS, Covert RF. Prophylactic indomethacin alters gentamicin pharmacokinetics in preterm infants <1250 grams. Pediatr Res (1994) 35, 83A. 

Engineer MS, Bodey GP, Newman RA, Ho DH. Effects of cisplatin-induced nephrotoxicity on gentamicin pharmacokinetics in rats. DrugMetab Dispos( 9Zl) 15, 329-34. 

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). 

Erichleb, M., Pharmacokinetics of gentamicin administered intratracheally or as an inhalation aerosol to guinea pigs, Drug Metab. Dispos. 1984, 12, 641-614. 

Pharmacokinetics What the patient does to the drug. For example, a patient with renal failure will have diminished renal clearance of gentamicin. 

As mentioned earlier, pharmacokinetics is not solely the property of a drug but instead is the consequence of interactions between the drug and the physiology of the patient. Thus, statements like the half-life of gentamicin is 2 hours are not very useful, as the half-life is likely be longer or shorter in a given individual patient. 

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. 

The pharmacokinetic properties of tobramycin are virtually identical with those of gentamicin. The daily dose of tobramycin is 5-6 mg/kg intramuscularly or intravenously, traditionally divided into three equal amounts and given every 8 hours. Monitoring blood levels in renal insufficiency is an essential guide to proper dosing. 

Detailed pharmacokinetic studies were performed on transscleral iontophoresis of various drugs [38-40,42,75-78]. Each drug resulted in different patterns of distribution in the vitreous. Carboplatin distribution in the vitreous after iontophoretic delivery demonstrated heightened levels in a controlled manner from 1 to 6 h after treatment [39], Foscarnet iontophoresis demonstrated a very low elimination rate, thus therapeutic levels in the vitreous were maintained for up to 60 h [78]. Methylprednisolone obtained a relatively low peak concentration 2 h after treatment [38], and gentamicin showed a peak concentration 16 h after the transscleral iontophoresis [42]. 

Baeyens, V., Kaltsatos, V., Boisrame, B., Fathi, M., and Gurny, R. (1998), Evaluation of soluble Bioadhesive Ophthalmic Drug Inserts (BODI) for prolonged release of gentamicin Lachrymal pharmacokinetics and ocular tolerance, J. Ocul. Pharmacol. Ther., 14(3), 263-272. 

Disposition in the Body. Poorly absorbed after oral administration but rapidly absorbed after intramuscular injection it is also absorbed systemically following topical application to wounds. In normal subjects it is rapidly excreted in the urine as unchanged drug, up to 80% of a dose being excreted in 24 hours. It accumulates in the tissues and there may be considerable intersubject variation in the pharmacokinetics. Gentamicin may be detected in serum and urine for several days after cessation of treatment. 

Tobramydtt. The antibacterial activity and pharmacokinetic properties of tobramycin resemble those of gentamicin, and the therapeutic uses of tobramycin are essentially identical to those for gentamicin. Although some bacteria are resistant to both gentamicin and tobramycin, it is impredictable in individual strains. Amikacin is usually effective for infections caused by organisms resistant to both gentamicin and tobramycin. 

FIGURE 3.7 Decline in serum gentamicin concentrations after therapy was stopped in a patient with nephrotoxicity ( ) and a patient who did not have this adverse reaction (o). Both patients had been treated with gentamicin at an S-hour dosing interval and had nearly identical elimination-phase half-lives and peak and trough levels. (Reproduced with permission from Colburn WA, Schentag JJr Jusko WJ, Gibaldi M. J Pharmacokinet Biopharm 1978 6 179-86.)... 

Schentag JJ, Jusko WJ, Vance JW, Cumbo TJ, Abrutyn E, DeLattre M, Gerbracht LM. Gentamicin disposition and tissue accumulation on multiple dosing. J Pharmacokinet Biopharm 1977 5 559-77. 

Colburn WA, Schentag JJ, Jusko WJ, Gibaldi M. A model for the prospective identification of the prenephrotoxic state during gentamicin therapy. J Pharmacokinet Biopharm 1978 6 179-86. 

Atkinson AJ Jr. Gentamicin kinetics A simulation case study. In Foster DM, Atkinson AJ Jr. Principles of pharmacokinetic data analysis Modeling and simulation (workshop manual). Seattle SAAM Institute, Inc. 2004. 

MaUet, A. Mentre, F. Gilles, J. Kelman, A.W. Thomson, A.N. Bryson, S.M. Whiting, B. Handling covariates in Population pharmacokinetics with an application to gentamicin. Biomed. Meas. Inform. Contr. 1988, 2, 673-683. 

Dodge, W.F. Jellife, R.W. Richardson, C.J. McCleery, R.A. Hokanson, J.A. Snodgrass, W.R. Gentamicin population pharmacokinetic models for low birth weight infants using a new non-parmaetric method. Clin. Pharmacol Ther. 1991, 50 (1), 25-31. 

Kisor, R.W. Gomis, P. Schumitzky, A. A Population Model of Gentamicin Made with a New Non-Parametric EM Algorithm Technical Report 90-4 Laboratory for Applied Pharmacokinetics, USC School of Medicine Los Angeles, CA, U.S.A. 

Careful tailoring of the dose can prevent nephrotoxicity. In 89 critically ill patients with a creatinine clearance over 30 ml/minute who were treated with gentamicin or tobramycin 7 mg/kg/day independent of renal function, with subsequent doses chosen on the basis of the pharmacokinetics of the first dose, signs of renal impairment occurred in 14% in all survivors renal function recovered completely and hemofiltration was not needed (104). 

Schentag JJ, Plaut ME, Cerra FB. Comparative nephrotoxicity of gentamicin and tobramycin pharmacokinetic and clinical studies in 201 patients. Antimicrob Agents Chemother 1981 19(5) 859-66. 

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