Tobramycin pharmacokinetics

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. 

Bauer LA, Piecoro JJ, Wilson HD, Blouin RA. Gentamicin and tobramycin pharmacokinetics in patients with cystic fibrosis. Clin Pharm 1983 2 262-264. 

Sampliner R, Perrier D, Powell R, Einley P. Influence of ascites on tobramycin pharmacokinetics. J Clin Pharmacol 1984 24 43-46. 

Matzke GR, Luckham DR, Collins AJ, Halstenson CE. Effect of ticarcillin on gentamicin and tobramycin pharmacokinetics in a patient with end-stage renal disease. Pharmacotherapy 1984 4 158-160. 

In summary, tobramycin pharmacokinetics were best characterized with a 2-compartment model where CL was proportional to CrCL and VI was proportional to body weight. BSV in CL was 29% with 13% variability across occasions. Residual variability was small, 14%, which compares well to assay variability of <7.5%. The model was robust to estimation algorithm and was shown to accurately predict an internally derived validation data set not used in the model development process. 

Hatfield SM, Crane LR, Duman K, Karanes C, Kiel RJ. Miconazole-induced alteration in tobramycin pharmacokinetics. ClinPharm (1986) 5, 415-19. 

Lau A, Lee M, Flascha S, Prasad R, Sharifl R. Effect of piperacillin on tobramycin pharmacokinetics in patients with nmnal renal function. Antimicrob Agents ChemoJrer (1983) 24, 533-7. 

Inhaled tobramycin (TOBI ) is typically administered to patients 6 years of age and older in alternating 28-day cycles of 300 mg nebulized twice daily, followed by a 28-day washout or off period to minimize development of resistance. Longterm intermittent administration improves pulmonary function, decreases microbial burden, and reduces the need for hospitalization for IV therapy.24,25 Due to minimal systemic absorption, pharmacokinetic monitoring is not necessary with normal renal function. Lower doses of nebulized tobramycin solution for injection have been used in younger children, and studies are underway using 300 mg twice daily in children under age 6. 

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. 

Tobramycin In vivo—rats In vivo—rats In vitro In vivo—mice In vivo—rats Pharmacokinetics Pharmacokinetics, eradication of P. aeruginosa Drug release, effect of lipid composition Pharmacokinetics, effect of lipid composition Pharmacokinetics, eradication of P. aeruginosa [88] [87] [90] [89]... 

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. 

Bourget P, Fernandez H, Delouis C, Taburet AM. Pharmacokinetics of tobramycin in pregnant women, safety and efficacy of a once-daily dose regimen. J Clin Pharm Ther 1991 16 167-76. 

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). 

The pharmacokinetics of once-daily intravenous tobramycin have been investigated in seven children with cystic fibrosis (162). All responded well. There was one case of transient ototoxicity but no nephrotoxicity. 

Bragonier R, Brown NM. The pharmacokinetics and toxicity of once-daily tobramycin therapy in children with cystic fibrosis. J Antimicrob Chemother 1998 42(l) 103-6. 

The pharmacokinetics of tobramycin in patients with cystic fibrosis is significantly altered after lung transplantation, and early and close drug monitoring is recommended (43). 

Geller DE, Pitlick WH, Nardella PA, Tracewell WG, Ramsey BW. Pharmacokinetics and bioavaUabihty of aerosolized tobramycin in cystic fibrosis. Chest 2002 122(l) 219-26. 

Beringer PM, Vinks AA, Jelliffe RW, Shapiro BJ. Pharmacokinetics of tobramycin in adults with cystic fibrosis implications for once-daily administration. Antimicrob Agents Chemother 2000 44(4) 809-13. 

Manley HJ, Bailie GR, Frye R, Hess LD, McGoldrick MD. Pharmacokinetics of intermittent intravenous cefazolin and tobramycin in patients treated with automated peritoneal dialysis. J Am Soc Nephrol 2000 11(7) 1310-16. 

Touw DJ, Jacobs FA, Brimicome RW, Heijerman HG, Bakker W, Briemer DD. Pharmacokinetics of aerolized tobramycin in adult patients with cystic fibrosis. Antimicrob Agents Chemother 41 184-187, 1997. 

The first step is to estimate this patient s pharmacokinetic parameters of tobramycin on the basis of published population data. The volume of distribution in this patient is 23.1 L (0.33 L/kg x 70 kg), and his residual total body clearance (CLres) estimated from the relationship between CL and creatinine clearance [CLres = CLcr X 0.98] is 3 mL/min or 0.176 L/h. The elimination rate constant can be approximated as ... 

Xuan et al. (2000) reported on the pharmacokinetics of tobramycin in 327 adult hospitalized patients. The pharmacokinetics of tobramycin were consistent with the following 1-compartment model... 

Jernigan, Hatch, and Wilson (1988) studied the pharmacokinetics of tobramycin after intramuscular administration in cats. Bioavailability was estimated at 102.5% with maximal concentrations occurring within about an hour. Hence, tobramycin absorption appears rapid and complete. There are few papers modeling the intramuscular absorption of drugs. Swabb et al. (1983) modeled the intramuscular administration of aztreonam, another antibiotic, in humans and found that a simple first-order absorption was adequate to explain the rapid (time to maximal concentrations was 0.88 h) and complete (101% bioavailability) absorption. Similarly, Krishna et al. (2001) also found that first-order absorption was sufficient to model the pharmacokinetics of quinine after intramuscular administration. In both cases, the drugs were formulated in water. 

Aarons, L., Vozeh, S., Wenk, M., Weiss, P., and Follath, F. Population pharmacokinetics of tobramycin. British Journal of Clinical Pharmacology 1989 38 305-314. 

Jernigan, A.D., Hatch, R.C., and Wilson, R.C. Pharmacokinetics of tobramycin in cats. American Journal of Veterinary Research 1988 49 608-612. 

Naber, K.G., Westenfelder, S.R., and Madsen, P.O. Pharmacokinetics of the aminoglycoside antibiotic tobramycin in humans. Antimicrobial Agents and Chemotherapy 1973 3 469 173. 

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