Extended-Interval dosing of tobramycin in neonates: Implications for therapeutic drug monitoring

Hoog, Matthijs de; Mouton, Johan W.; Schoemaker, Rik C.; Verduin, Cees M.; Anker, John N. van den

doi:10.1067/mcp.2002.123595

Cited by 35 publications

(26 citation statements)

References 38 publications

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“…Pharmacokinetic parameters such as Vd and Cl are not modified in the extended time interval. The extended interval is also reported for netilmicin [33] and tobramycin [40].…”

Section: Discussionmentioning

confidence: 77%

“…There is a remarkable variation in the pharmacokinetic parameters of gentamicin [21,50], netilmicin [30][31][32]38], tobramycin [39,40] and amikacin [51,52]. Such a variation is due to renal maturation [50] as aminoglycosides are fairly water soluble and are eliminated with the urine.…”

Section: Discussionmentioning

confidence: 99%

“…Tobramycin MIC 90 values for Escherichia coli and for Klebsiella pneumoniae are 0.5 and 1 μg/ml respectively [5]; and assuming a peak-to-MIC 90 ratio above 10, a peak tobramycin serum concentration higher than 10 μg/ml should be desirable [40]. What has been stated for gentamicin holds true for tobramycin as well: t 1/2 is greater in the premature than full-term neonate and the opposite is true for Cl [39].…”

Section: Discussionmentioning

confidence: 99%

“…Using these dosages, the majority of infants had tobramycin peak concentrations from 5 to 10 μg/ml and trough concentrations from 0.5 to 1 μg/ml. The elimination rate constant (Ke) was 0.064±0.034 and 0.098±0.046 h -1 at gestational ages <32 and ≥37 weeks respectively; and Vd was 0.70±0.17 and 0.54±11 l/kg at the gestational ages of <32 and ≥37 weeks respectively [40]. The difference in Cl reflects the reduced clearance of tobramycin in preterm neonates [41][42][43].…”

Section: Tobramycinmentioning

confidence: 99%

“…Using this schedule, the percentage of trough concentrations >2 μg/ml ranged from 19 to 49%. In a successive study, de Hoog et al [40] administered 4 mg/kg tobramycin to all patients and the interval between doses was 48 h (<32 weeks), 36 h (32-36 weeks) and 24 h (≥37 weeks). Using these dosages, the majority of infants had tobramycin peak concentrations from 5 to 10 μg/ml and trough concentrations from 0.5 to 1 μg/ml.…”

Section: Tobramycinmentioning

confidence: 99%

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Clinical pharmacokinetics of aminoglycosides in the neonate: a review

Pacifici

2008

Eur J Clin Pharmacol

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Background Sepsis is common in neonates and is a major cause of morbidity and mortality. Sixty percent of preterm neonates receive at least one antibiotic, and 43% of the antibiotics administered to these neonates are aminoglycosides. The clearance (Cl), serum half-life (t 1/2 ), and volume of distribution (Vd) of aminoglycosides change during the neonatal life, and the pharmacokinetics of aminoglycosides need to be studied in neonates in order to optimise therapy with these drugs. Objective The aim of this work is to review the published data on the pharmacokinetics of aminoglycosides in order to provide a critical analysis of the literature that can be a useful tool in the hands of physicians. Methods The bibliographic search was performed electronically using PubMed, as the search engine, through July 11th, 2008. Firstly, a Medline search was performed with the keywords "pharmacokinetics of aminoglycosides in neonates" with the limit of "human". Other Medline searches were performed with the keywords "pharmacokinetics of … in neonates" followed by the name of the aminoglycosides: amikacin, gentamicin, netilmicin and tobramycin. In addition, the book Neofax: A Manual of Drugs Used in Neonatal Care by Young and Mangum (Thomson Healthcare, 2007) was consulted. Results The aminoglycosides are mainly eliminated by the kidney, and their elimination rates are reduced at birth. As a consequence Cl is reduced and t 1/2 is prolonged in the neonate as compared to more mature infants. The high body-water content of the neonate results in a large Vd of aminoglycosides as these drugs are fairly water soluble. Postnatal development is an important factor in the maturation of the neonate, and as postnatal age proceeds, Cl of aminoglycosides increases. Conclusion The maturation of the kidney governs the pharmacokinetics of aminoglycosides in the infant. Cl and t 1/2 are influenced by development, and this must be taken into consideration when planning a dosage regimen with aminoglycosides in the neonate. Aminoglycosides are fairly water soluble, and the larger water content of neonates yields a larger Vd in these patients.

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“…Pharmacokinetic parameters such as Vd and Cl are not modified in the extended time interval. The extended interval is also reported for netilmicin [33] and tobramycin [40].…”

Section: Discussionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Tobramycinmentioning

confidence: 99%

Section: Tobramycinmentioning

confidence: 99%

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Clinical pharmacokinetics of aminoglycosides in the neonate: a review

Pacifici

2008

Eur J Clin Pharmacol

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Neonatal Antimicrobials

2013

Evidence‐Based Neonatal Infections

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Developmental pharmacology

Anker

2010

Dev Disabil Res Revs

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Understanding the pharmacokinetics and pharmacodynamics of drugs used in psychopharmacology across the pediatric age spectrum from infants to adolescents represents a major challenge for clinicians. In pediatrics, treatment protocols use either standard dose reductions for these drugs for children below a certain age or use less conventional parameters such as weight for allometric dosing. The rationale behind this, however, is often lacking. In this review current available data on the developmental changes in absorption, distribution, metabolism, and elimination of drugs are presented with a specific focus on metabolic pathways, indicating significant differences in the development of enzymes involved in the biotransformation of drugs used in psychopharmacology. Major emphasis will be given to the genetic variation in CYP2D6 activity, the most important enzyme for the metabolism of many psychotropic medications. Finally, this review will summarize the role of the developmental pharmacologist in ensuring rational use of drugs in children with developmental disabilities and in translating pharmacological concepts from the bench to the clinic.

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Extended-Interval dosing of tobramycin in neonates: Implications for therapeutic drug monitoring

Abstract: Routine early therapeutic drug monitoring does not improve the model-based prediction of initial tobramycin dosing intervals in neonates in the first week of life.

Cited by 35 publications

References 38 publications

Clinical pharmacokinetics of aminoglycosides in the neonate: a review

Clinical pharmacokinetics of aminoglycosides in the neonate: a review

Neonatal Antimicrobials

Developmental pharmacology

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