Kinetics of netilmicin in man

Péchère, Jean-Claude; Dugal, Robert; Pechere, Marie-Madeleine

doi:10.1002/cpt1978236677

Cited by 28 publications

(20 citation statements)

References 2 publications

(3 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cumulative urinary excretion in our study (70 to 85%) also compares closely with those of other investigators (1,5,6), which were 69 to 80%. Total body clearance calculated from our data was comparable to that reported in two studies (3,5).…”

Section: Resultssupporting

confidence: 91%

“…2) constant for netilnicin, calculated by a two-compartment model (5), have been reported. After intravenous administration of the drugs, the pharmacokinetics of gentamicin (1, 7) and netilmicin (3,5,7,11) have been described by a twocompartment model.…”

Section: Resultsmentioning

confidence: 99%

“…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%

See 2 more Smart Citations

Comparison of netilmicin and gentamicin pharmacokinetics in humans

Chung¹,

Costello²,

Symchowicz³

1980

Antimicrob Agents Chemother

View full text Add to dashboard Cite

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.

show abstract

Section: Resultssupporting

confidence: 91%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Comparison of netilmicin and gentamicin pharmacokinetics in humans

Chung¹,

Costello²,

Symchowicz³

1980

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…To our knowledge, two-compartment model pharmacokinetics have not been applied to aminoglycosides in the neonate, although there have been reports of this model for netilmicin (17,20,30), sisomicin (20), tobramycin (20), and gentamicin (3,25) in adults and older children. We analyzed the serum concentrations obtained during the steady state by both the one-and two-compartment models and found that the former model provided the best fit.…”

Section: Netilmicin In Newborn Infants 251mentioning

confidence: 99%

“…We have also measured netilmicin in serum and/or urine for as long as 12 days after discontinuation of therapy and have fit these data to a two-compartment model as has been described for aminoglycosides in older children and adults (3,17,20,25,30).…”

mentioning

confidence: 99%

Pharmacokinetic Properties of Netilmicin in Newborn Infants

Siegel

McCracken

Thomas

et al. 1979

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Netilmicin and gentamicin susceptibilities of 258 gram-negative organisms and 25 strains of Staphylococcus aureus were nearly identical. The pharmacokinetic properties of netilrnicin were evaluated in 101 newborn infants and related to birth weight, gestational age, chronological age, and route of administration. Mean peak serum concentrations of 5.6 to 6.9 and 7.8 to 8.4 ,ug/ml were observed 30 min after 3-and 4-mg/kg doses, respectively, were given intramuscularly. The peak concentrations were directly related to gestational age. The average serum half-life values varied from 3.4 to 4.7 h and in general were inversely related to birth weight, gestational age, and postnatal age. The pharmacokinetics of netilmicin in 10 infants were similar after intramuscular and intravenous administration. A comparative study of netilmicin and gentamicin in seven neonates revealed greater variability in serum concentrations of gentamicin and a shorter half-life for netilmicin. There was evidence of accumulation of netilmicin in 12 low-birth weight, premature infants who received 4-mg/kg doses for an average of 6.4 days. Serum and urine levels of netilmicin were measured up to 11 days after discontinuation of the drug. These data are well characterized by a two-compartment model. Additional studies of efficacy and long-term toxicity of netilmicin in neonates are necessary.Netilmicin is a new semisynthetic aminoglycoside that is a 1-N-ethyl sisomicin derivative produced by Micromonospora inyoensis. Its antimicrobial spectrum is similar to that of gentamicin with an added advantage that an increasing number of Enterobacteriaceae possess adenylating enzymes mediating resistance to gentamicin, but not to netilmicin (4,10,16,21,28). Animal studies indicate that substantially less ototoxicity and nephrotoxicity result from repeated doses of netilmicin than of gentamicin (9,12,16). In an experimental rabbit model ofEscherichia coli meningitis, netilmicin has also been shown to have greater bactericidal activity in cerebrospinal fluid' than does gentamicin (24). These observations suggest that netilmicin may be potentially useful for therapy of neonatal bacterial infections.In this study we have evaluated the pharmacokinetics of netilnicin in 101 neonates and related these properties to birth weight, gestational age, chronological age, and route of administration. We have also measured netilmicin in serum and/or urine for as long as 12 days after discontinuation of therapy and have fit these data to a two-compartment model as has been described for aminoglycosides in older children and adults (3,17,20,25,30). MATERIALS AND METHODSSusceptibility studies. The susceptibilities to gentamicin and netilmicin of 258 gram-negative organisms and 25 Staphylococcus aureus strains isolated from blood, cerebrospinal fluid, or urine of sick neonates and from rectal culture of normal newborns were determined by a modified agar plate dilution method (1) with a multiple inoculating apparatus (27). Serial twofold dilutions of laboratory standards of net...

show abstract

Netilmicin Sulfate: A Comparative Evaluation of Antimicrobial Activity, Pharmacokinetics, Adverse Reactions and Clinical Efficacy

1983

View full text Add to dashboard Cite

Netilmicin, the 1-N-ethyl derivative of sisomicin, is a new aminoglycoside antibiotic that was recently marketed in the United States. Its role in therapeutics is not yet established. The pharmacokinetic profile of netilmicin is very similar to that of gentamicin. Its antimicrobial spectrum and clinical efficacy is similar to that of gentamicin, tobramycin and amikacin. It is less active in vitro against Pseudomonas aeruginosa that gentamicin and tobramycin, but in clinical trials the efficacy of netilmicin against the organism has been similar to other aminoglycosides. Netilmicin is active against some gentamicin and tobramycin-resistant strains of gram-negative bacilli, particularly those harboring adenylating and phosphorylation enzymes. Most of these strains are sensitive to amikacin as well, and amikacin is also active against most netilmicin-resistant strains of these bacteria. Therefore, amikacin remains the aminoglycoside of choice against gentamicin tobramycin and netilmicin-resistant gram-negative bacilli. In comparison to other currently available aminoglycosides, a lower frequency of nephrotoxicity and ototoxicity has been observed in laboratory animals given netilmicin. This has not been unequivocally demonstrated in humans. The frequency of nephrotoxicity in humans has been similar to that of other aminoglycosides. The frequency of ototoxicity associated with netilmicin in humans has been low but not significantly less than in other aminoglycosides, except in one trial. If further studies document a significantly lower frequency of ototoxicity with netilmicin, it may become the aminoglycoside of choice for patients with significant risk factors for ototoxicity, such as advanced age, renal impairment, concomitant ototoxic drug therapy and prolonged aminoglycoside administration.

show abstract

Kinetics of netilmicin in man

Cited by 28 publications

References 2 publications

Comparison of netilmicin and gentamicin pharmacokinetics in humans

Comparison of netilmicin and gentamicin pharmacokinetics in humans

Pharmacokinetic Properties of Netilmicin in Newborn Infants

Netilmicin Sulfate: A Comparative Evaluation of Antimicrobial Activity, Pharmacokinetics, Adverse Reactions and Clinical Efficacy

Contact Info

Product

Resources

About