Comparative Clinical Pharmacology of Gentamicin, Sisomicin, and Tobramycin

In a crossover study, single doses of netilmicin and gentamicin were administered intramuscularly, each at 1.0 and 2.5 mg/kg. The serum concentrations, analyzed by a two-compartment open model with a first-order absorption, indicated that the pharmacokinetics of the drugs are essentially the same. Both drugs were rapidly absorbed and distributed after administration. No significant differences were observed between the two drugs in disposition half-life, rate of distribution and elimination, area under the serum concentration-time curve, urinary excretion, total body clearance, and renal clearance. After 1.0 mg/kg, the maximum serum concentration of netilmicin (5.18 ,ug/ml) was only slightly lower than that for gentamicin (5.76 ylg/ml), but no difference was found after the 2.5-mg/kg dose.

Section: Resultssupporting

confidence: 80%

“…The pharmacokinetics of gentamicin in humans have been documented (1,6,7,10), and more recently those of netilmicin have been reported J3, 5,7,11). Most of these pharmacokinetic studies were based on serum concentrations obtained during the first 8 h after intravenous infusion of the drugs, using a one-or twocompartment open model.…”

mentioning

confidence: 99%

Comparison of netilmicin and gentamicin pharmacokinetics in humans

Chung¹,

Costello²,

Symchowicz³

1980

“…To detect a possible saturation effect of interstitial tissue fluid for each drug, we have compared, two by two, the levels obtained at 8,16,24,32, and 48 h. Repeated injections did not significantly increase the interstitial fluid levels of gentamicin. With the other drugs, interstitial fluid levels continued to increase until the third or fourth injection.…”

Section: Methodsmentioning

confidence: 99%

“…Different patterns of antimicrobial activity have been shown for these different drugs, which are more or less sensitive to bacterial enzyme degradation (9,11,15,19,23,25,28). All these agents have similar pharmacokinetic properties in humans (7,14,16,20,21). Some discrepancies between these antibiotics as to their toxicity have been outlined (2,24,27).…”

mentioning

confidence: 99%

Comparative distribution of gentamicin, tobramycin, sisomicin, netilmicin, and amikacin in interstitial fluid in rabbits

Carbon¹,

Contrepois²,

Lamotte-Barrillon³

1978

We compared the penetration of five aminoglycosides into interstitial fluid (IF). IF was obtained in rabbits from Silastic tissue cages. Intramuscular injections were made: 1.5 mg/kg per dose for gentamicin (G), tobramycin (T), sisomicin (S), and netilmicin (N) and 7.5 mg/kg per dose for amikacin (A). Serum levels and IF concentrations were studied for 12 h after a single injection. IF levels were also compared in a six-injection study (one injection every 8 h). Peak serum levels were significantly higher with A than with G, T, S, and N, which gave similar concentrations. In IF, G gave the highest levels 1 h after the first injection. At 4 and 8 h, the concentrations achieved with G and A were similar but significantly greater than those achieved with T, S, and N. Twelve hours after a single injection, N gave higher IF levels than the other drugs except A. In the six-injection study, the IF levels of G and A reached 4.6 +/- 1.5 and 5.27 +/- 1.1 microgram/ml, respectively, at 48 h. S and N gave identical concentrations (2.07 +/- 0.25 and 2.42 +/- 0.42 microgram/ml, respectively). T induced the lowest levels (1.17 +/- 0.30 microgram/ml). Thus, in this rabbit model, the IF concentrations achieved with G and A were above the minimal inhibitory concentrations for most susceptible strains. Possible relations between IF aminoglycoside concentrations and therapeutic efficiency or toxicity are pointed out but deserve further studies.

“…However, as with the other aminoglycosides, the danger of neurotoxicity and nephrotoxicity exists at high serum concentrations (3,5,6,8,9). It is therefore very important to monitor serum levels of the antibiotic to assure adequate yet nontoxic dosage (4, 11).…”

mentioning

confidence: 99%

Assay of serum tobramycin levels with the Bactec 460

Phillips¹,

Martin²,

Gentry³

et al. 1979

Serum tobramycin levels of synthetic and patient specimens were determined by the Bactec 460. The results were compared with those obtained from the same specimens by radioimmunoassay. These studies suggest that assays performed by either method should be run in duplicate or triplicate to achieve maximum accuracy. The studies also suggest that results obtained by the Bactec method are at least as reliable as those obtained by the radioimmunoassay method.Tobramycin is one of several aminoglycosides available for therapeutic use in serious infections caused by gram-negative bacilli. However, as with the other aminoglycosides, the danger of neurotoxicity and nephrotoxicity exists at high serum concentrations (3,5,6,8,9). It is therefore very important to monitor serum levels of the antibiotic to assure adequate yet nontoxic dosage (4, 11). Other methods available for the measurement of serum tobramycin levels (disk diffusion bioassay, enzymatic assay, and radioimmunoassay [RIA]) are for the most part tedious, expensive, time consuming, or all three. The need has existed for a rapid, reliable method for determining serum tobramycin levels which is economical and does not involve additional laboratory equipment or slow assay procedures. The Bactec 460 (Johnston Laboratories, Cockeysville, Md.) may be useful in this regard in laboratories which process many blood cultures as part of their normal work load. Although the main application of the instrument is the early detection of sepsis, it may be used with an auxiliary kit to determine tobramycin levels within 2 h.Following are the results of a study conducted in this laboratory to determine four main aspects concerning tobramycin serum measurements with the Bactec 460: (i) the within-day reproducibility, (ii) the day-to-day reproducibility and long-term stability, (iii) the accuracy of the determinations by comparison with expected values, and (iv) comparison with another widely used method of tobramycin serum analysis, namely RIA. MATERIALS AND METHODSAssays were performed by the manufacturer's instructions (7) A 0.2-ml amount of the aqueous standard tobramycin solutions, measured with a tuberculin syringe, was added to vials containing base solution. The standard concentrations were 0.87, 1.75, 3.5, 7, and 14 ug/ ml. A 0.2-ml quantity of the test or patient sample was added to additional vials. Subsequently, 0.2 ml of normal pooled human serum was added to each of the vials containing standard solutions, and 0.2 ml of sterile, deionized water was added to the test vials to attain uniform consistency in all vials. To begin the assay, 0.2 ml of a standardized Proteus working solution supplied with the kit was added to each vial, which was gently swirled by hand and placed in a 35°C water bath. The inoculated vials were allowed to incubate for 60 min, after which 0.5 ml of stopper solution (0.5 N HCl with a 1% antifoam agent) was added to each in the same order in which the Proteus had been added.