Population pharmacokinetics of intravenous indomethacin in neonates with symptomatic patent ductus arteriosus

Wiest, Donald B.; Pinson, J B; Gál, Péter; Brundage, Richard C.; Schall, Stewart A.; Ransom, J. Laurence; Weaver, Richard L.; Purohit, Dilip M.; Brown, Yvonne

doi:10.1038/clpt.1991.65

Cited by 37 publications

(13 citation statements)

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“…Individual estimates for V in our population are in good agreement with those from previous studies [9, 10, 12, 13]. Each of our infants with a PNA ≥ 30 days ( n = 5) had an estimated V > 0.34 l kg −1 , which is above the lower limit of the reported range in adults (0.34–1.57 l kg −1 ) [27].…”

Section: Discussionsupporting

confidence: 89%

“…Since then its use in the treatment of clinically significant PDA has been widely documented, but the response to treatment has been extremely variable [7][8][9][10][11]. Studies of indometacin in the newborn have also reported considerable interindividual variability in its pharmacokinetics [9,10,[12][13][14][15][16]. Traditional pharmacokinetic studies are difficult to perform in infants because of the need for multiple blood samples, which creates ethical and technical problems.…”

Section: Introductionmentioning

confidence: 99%

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Intravenous indometacin in preterm infants with symptomatic patent ductus arteriosus. A population pharmacokinetic study

Smyth¹,

Collier²,

Darwish³

et al. 2004

Brit J Clinical Pharma

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AimsTo characterize the population pharmacokinetics of indometacin in preterm infants with symptomatic patent ductus arteriosus and to investigate the influence of various factors on the response to treatment. MethodsData were collected from 35 infants (gestational age 25-34 weeks; postnatal age 1-77 days) in neonatal units in Belfast and Copenhagen. Infants received an initial course of up to three doses of intravenous indometacin (0.1-0.2 mg kg -1 ) as considered appropriate by the treating physician. For those infants who did not respond to therapy or in whom the ductus reopened, a second course was sometimes g iven. Population analysis of the 185 plasma concentrations obtained was conducted using NONMEM and pharmacokinetic and demographic differences between responders and nonresponders were compared. ResultsThe concentration-time course of indometacin was best described by a one-compar tment model. The final population parameter estimates of clearance (CL) and volume of distribution (V) (standardized to the median weight of 1.17 kg) were 0.00711 l h -1 and 0.266 l, respectively. CL increased from birth by approximately 3.38% per day and V by approximately 1.47% per day. Concomitant digoxin therapy resulted in a 30% decrease in V. Interindividual variability in CL and V was 41% and 21%, respectively. Interoccasion variability for CL was 43%. Residual variability corresponded to a standard deviation of 0.148 mg l -1 . Closure occurred in 75% of infants with a plasma concentration ≥ 0.4 mg l -1 24 h after the last dose. ConclusionsDosing regimens for indometacin should take into account the weight and postnatal age of the infant and any concomitant digoxin therapy. The population estimates can be used to determine typical values of CL and V allowing the prediction of individualized doses of indometacin that should increase the probability of achieving a 24 h plasma concentration ≥ 0.4 mg l -1 . Although the pharmacokinetic estimates will be affected by both interindividual and within-individual variation, it is anticipated that this approach will decrease the variability of exposure and optimize treatment outcome.J. M. Smyth et al. 25058 :3 Br J Clin Pharmacol

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Intravenous indometacin in preterm infants with symptomatic patent ductus arteriosus. A population pharmacokinetic study

Smyth¹,

Collier²,

Darwish³

et al. 2004

Brit J Clinical Pharma

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“…The lack of data on the pharmacokinetics of many drugs in neonates and children is related to blood sampling limitations for this population. One way around this problem is to collect a few samples from many individuals and analyze the data by means of a population-based approach (7,10,13,14,29,34,51,54). The administration of aminoglycosides once daily has been shown to be as well tolerated as or better tolerated than the conventional schedules (twice daily or thrice daily) in adults and children.…”

mentioning

confidence: 99%

Nonparametric Population Pharmacokinetic Analysis of Amikacin in Neonates, Infants, and Children

Tréluyer

Merlé

Tonnelier

et al. 2002

Antimicrob Agents Chemother

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The therapeutic and toxic effects of amikacin are known to depend on its concentration in plasma, but the pharmacokinetics of this drug in neonates, infants, and children and the influences of clinical and biological variables have been only partially assessed. Therapeutic drug monitoring data collected from 155 patients (49 neonates, 77 infants, and 29 children) receiving amikacin were analyzed by a nonparametric population-based approach, the nonparametric maximum-likelihood method. We assessed the effects of gestational and postnatal age, weight, Apgar score, and plasma creatinine and urea concentrations on pharmacokinetic parameters. There is no specific formulation of amikacin for neonates and infants. We therefore used an error model to account for errors due to dilution during preparation of the infusion. The covariates that reduced the variance of clearance from plasma and the volume of distribution by more than 10% were postnatal age (43 and 28%, respectively) and body weight (30.4 and 17.4%, respectively). The expected reduction of clearance was about 10% for the plasma creatinine concentration. The other covariates studied (Apgar scores, plasma urea concentration, gestational age, sex) were found to have little effect. Simulations showed that a smaller percentage of patients had a maximum concentration in plasma/MIC ratio greater than 8 with a regimen of 7.5 mg/kg of body weight twice daily than with a regimen of 15 mg/kg once a day for MICs of 1 to 8 mg/liter.Amikacin is widely used in neonates and infants, as well as in adults, for the treatment of severe infections caused by gramnegative bacteria. Previous studies have shown that both the therapeutic response and toxic effects depend on plasma amikacin concentrations. Achieving a therapeutic maximum concentration of amikacin in plasma is associated with a significant decrease in the rate of mortality due to infection in critically ill patients (2, 36, 37), and a relationship has also been found between the minimum plasma amikacin concentration and renal toxicity (20,49). Interindividual variability in the pharmacokinetics of amikacin may therefore make it difficult to achieve safe and effective treatment. The pharmacokinetics of aminoglycosides have been shown to be highly variable in neonates and children. Several factors account for the pharmacokinetic variabilities of other aminoglycosides in this population (50). The pharmacokinetics of netilmicin and gentamicin depend on gestational age, postnatal age, weight, renal clearance, and Apgar score (6,9,11,12,14,18,21,43,46,47,(51)(52)(53). Very few data are available concerning the effects of clinical and biological covariates on the pharmacokinetics of amikacin in neonates and the changes in the pharmacokinetic profile of amikacin that occur from birth into infancy. The lack of data on the pharmacokinetics of many drugs in neonates and children is related to blood sampling limitations for this population. One way around this problem is to collect a few samples from many individuals and analyze the...

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“…A utilização da IM para o tratamento farmacológico do fecho do CA em recém-nascidos foi descrita pela primeira vez em 1976 (Vert et al, 1980;Wiest et al, 1991), sendo hoje um dos fármacos de eleição efetivo e apropriado, induzindo o fecho do CA em mais de 80% dos recém-nascidos prematuros, quando administrado por via intravenosa (Angerio, Kot, 1998;Archer, 1993;Baptista et al, 1999;Bhatt, Nahata, 1989;Grosfeld et al, 1996;Hammerman, 1995).…”

Section: Indometacina Como Fármaco De Escolha No Tratamento Farmacolóunclassified

Aspectos biofarmacêuticos da formulação de medicamentos para neonatos: fundamentos da complexação de indometacina com hidroxipropil-beta-ciclodextrina para tratamento oral do fechamento do canal arterial

Rama¹,

Veiga²,

Figueiredo³

et al. 2005

Rev. Bras. Cienc. Farm.

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INTRODUÇÃOA investigação farmacêutica tem como intuito o desenvolvimento de novos agentes terapêuticos direcionados à resolução de situações clínicas, integrando conhecimentos pluridisciplinares.A prática de cuidados farmacêuticos possibilita a identificação de situações clínicas para as quais os recursos terapêuticos existentes não são os adequados. Fazer parte da equipe de saúde de uma unidade de cuidados intensivos de neonatologia é um desafio para o farmacêu-tico clínico, confrontado com a necessidade de dar resposta aos problemas biofarmacêuticos decorrentes da anatomofisiologia e das patologias inerentes àquele gru- Unitermos• Indometacina• Hidroxipropil-β-ciclodextrina• Recém-nascidos• Canal arterial

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Population pharmacokinetics of intravenous indomethacin in neonates with symptomatic patent ductus arteriosus

Cited by 37 publications

References 0 publications

Intravenous indometacin in preterm infants with symptomatic patent ductus arteriosus. A population pharmacokinetic study

Intravenous indometacin in preterm infants with symptomatic patent ductus arteriosus. A population pharmacokinetic study

Nonparametric Population Pharmacokinetic Analysis of Amikacin in Neonates, Infants, and Children

Aspectos biofarmacêuticos da formulação de medicamentos para neonatos: fundamentos da complexação de indometacina com hidroxipropil-beta-ciclodextrina para tratamento oral do fechamento do canal arterial

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