Tobramycin population pharmacokinetics in neonates*

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

doi:10.1016/s0009-9236(97)90117-x

Cited by 59 publications

(55 citation statements)

References 33 publications

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“…Since the peak plasma concentration of vancomycin was proportional to the dose and the rate of drug infusion, data presented agree with results reported by other investigators. 23 The mean biological half-life of 11.3 hours (IC95%, 9.3-13.3 hours) obtained for infants of group 1 (Table 4) agrees with those reported previously for newborns of 32 weeks or less PCA. However, it is important to emphasize that a larger variation is reported for the parameter (3.5-25.5 h, n = 44) in an investigation reported in a previous study.…”

Section: Discussionsupporting

confidence: 90%

Vancomycin Pharmacokinetics in Preterm Infants

Machado

Feferbaum

Kobayashi

et al. 2007

Clinics

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. Vancomycin pharmacokinetics in preterm infants. CLINICS. 2007;62(4):405-10. OBJETIVE:The objective of the present study was to evaluate the kinetic disposition of vancomycin in preterm infants with emphasis on the apparent volume of distribution, biological half-life, and total body clearance as well as whether their variations cause significant modification of the trough plasma concentration of the drug, depending on the postconceptional age (PCA) and the postnatal age (PNA). MATERIAL AND METHOD: Twenty-five selected patients were distributed into 2 groups which differed significantly in terms of mean PCA (31.2-32.3 weeks in group 1, n = 13; 33.5-34.1 weeks in group 2, n = 12: CI95%, P < .001) and PNA (group 1, 12.0-18.5 days; group 2, 18.0-34.0 days, CI95%, P < .05). The parents were informed and signed a written consent for participation of the infants in the protocol that had been previously approved by the Ethics Committee of the hospital. RESULTS: Apparent volume of distribution was significantly increased in group 1 compared with patients of group 2 (0.85 vs. 0.56 L/kg, respectively; P = .01,). Additionally multiple linear regression revealed a good linear correlation (r = 0.85) of trough plasma concentration of vancomycin with the apparent volume of distribution and also with the biological half-life in patients of group 1, while a good correlation (r = 0.91) was obtained for the trough plasma concentration with total body clearance in infants of group 2. The influence of these kinetic parameters on the trough concentration of vancomycin in preterm infants seems to vary according to PCA and PNA. CONCLUSION: In conclusion, the trough plasma concentration of vancomycin depends on the pharmacokinetics, and multiple linear correlation indicates that it varies according to the postconceptional and postnatal age of preterm infants.

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Section: Discussionsupporting

confidence: 90%

Vancomycin Pharmacokinetics in Preterm Infants

Machado

Feferbaum

Kobayashi

et al. 2007

Clinics

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“…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: 88%

“…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%

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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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“…Using these dosing regimens, plasma concentration profiles and associated 95% confidence intervals of the population variability were simulated. Since trough plasma vancomycin concentrations are important for antimicrobial efficacy, the aim was to maintain trough concentrations over the range 10 to 15 mg l -1 , and to avoid the lower and upper confidence intervals falling outside 5 and 20 mg l -1 , respectively [26]. Although mean plasma concentration profiles obtained in all simulations were acceptable, the confidence intervals indicate the difficulty in predicting vancomycin pharmacokinetics in an individual, a finding that reinforces the importance of therapeutic drug monitoring.…”

Section: Data Are Expressed As Mean (Sd)mentioning

confidence: 88%

Population pharmacokinetics of vancomycin in patients receiving extracorporeal membrane oxygenation

Mulla¹,

Pooboni

2005

Brit J Clinical Pharma

110

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AimsExtracorporeal membrane oxygenation (ECMO) is a life support system used during severe respiratory or cardiorespiratory failure. The objective of this study was to characterize the population pharmacokinetics of vancomycin during ECMO. MethodsA population model was developed using WinNonMix (Version 2.0.1) from a total of 366 plasma observations in 45 patients, including term neonates, older children and adults. The study utilized both rich prospective and sparse retrospective data. Prospective samples were drawn at baseline and then 30, 60,90, 120, 180, 240, 300, 360 and 420 min postinfusion. Steady state concentrations were obtained retrospectively from an assay database, cross-referencing with the patients' medical records. ResultsData were examined using a two-compartment model with an additive and proportional residual error. Model fit improved substantially when clearance, CL (l kg -1 h -1 ) was modelled as a nonlinear function of serum creatinine (Cr) m mol l -1 . There was a linear relationship between CL and age up to 1000 days: CL (Age < 1000 days) = [2.4 + 0.0018 ¥ Age (days)]/Cr; CL (Age > 1000 days) = 4.3/Cr. Age also influenced central volume ( V 1) when included in the model as a dichotomous variable: V 1 (Age < 4000 days) = 0.45 l kg -1 ; V 1 (Age > 4000 days) = 0.36 l kg -1 . Intercompartmental clearance and tissue volume were estimated to be 0.09 l kg -1 h -1 and 0.25 l kg -1 , respectively. Model validation in a separate group of 20 patients revealed a bias of -7.7% and a precision of 26.7%. ConclusionsThe clearance of vancomycin was decreased and its volume of distribution increased in patients receiving ECMO, suggesting altered drug disposition during this treatment.

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Tobramycin population pharmacokinetics in neonates*

Cited by 59 publications

References 33 publications

Vancomycin Pharmacokinetics in Preterm Infants

Vancomycin Pharmacokinetics in Preterm Infants

Clinical pharmacokinetics of aminoglycosides in the neonate: a review

Population pharmacokinetics of vancomycin in patients receiving extracorporeal membrane oxygenation

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