Total Body Digoxin Clearance and Steady-State
Concentrations in Low Birth Weight Infants

Rl, Collins-Nakai; Pk, Ng; Ma, Beaudry; Ocejo-Moreno, R; Schiff, David; Gr, Van Petten

doi:10.1159/000457391

Cited by 6 publications

(6 citation statements)

References 12 publications

(19 reference statements)

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“…Low incidence of digoxin toxicity in our LBW infants despite high serum levels is consistent with the previous observations [3,19]. The decreased sensitivity to digoxin toxicity in the very young may be partly explained by the finding of more 'receptors' for digoxin and their lower binding affinity for digoxin in newborns [9].…”

Section: Resultssupporting

confidence: 91%

“…first dose) are in agreement with those (35.0 ± 17.6 ml/min/1.73 m2) calculated from observed mean steady-state levels during multiple dosing [3]. These values are higher than those (4.7 ± 2.1 ml/min/1.73 m2) in a recent investigation [23].…”

Section: Resultssupporting

confidence: 90%

“…The longer digoxin half-life and lower TDBC in LBW infants than in full-term infants are probably due to the decrease in renal digoxin clearance in the former group [15]. Good correlation (r = 0.85) between TBDC and gestational age was also observed when we combined the data on TBDC and body weight of this study and our previous investigation [3]. If a 'target' mean steady-state blood level (Css) is chosen, the appropriate maintenance dose can be calcu lated to achieve the chosen Css according to the total body clearance [20].…”

Section: Resultssupporting

confidence: 68%

“…Numerous pharmacokinetic studies of digoxin in pediatric patients for the last 10 years have yielded valuable recommendations for digoxin dosage in neonates, infants and children [16,17], The few pharmacokinetic studies of digoxin done in low-birth-weight (LBW) infants have been limited to the determination of serum concentrations and half-lives [2,3,12,19]. A recent systematic study of digoxin kinetics in the LBW infants [23] reported a short half-life of digoxin (T'/zß) with a mean of 15.3 h which was 4-5 times lower than those of the previous studies [2,12,19].…”

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetics of Digoxin in Low-Birth-Weight Infants

Rl¹,

Schiff²,

Pk³

1982

Dev Pharmacol Ther

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Digoxin pharmacokinetics were studied in 13 low-birth-weight infants requiring digoxin therapy. Their weights ranged from 820 to 2,710 g (x̄ = 1,440 g) and gestational ages ranged from 26 to 38 weeks (x̄ = 30.9 weeks). The distribution and elimination of digoxin can be described by an open two-compartment model. Poor correlation between volume of distribution Vdβ (5.7 ± 1.0 liters/kg) and gestational age (GA) or weight (Wt) was observed. Digoxin half-life (47 ± 21 h) was inversely related to GA and Wt (r = 0.69 and 0.66, respectively), but total body digoxin clearance (29.8 ± 14.7 ml/min/1.73 m^2) was found to be highly dependent on these two variables (r = 0.87 and 0.88, respectively). According to the results of this study and our previous investigation, digitalizing and maintenance dosages of digoxin were recommended.

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Section: Resultssupporting

confidence: 91%

Section: Resultssupporting

confidence: 90%

Section: Resultssupporting

confidence: 68%

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetics of Digoxin in Low-Birth-Weight Infants

Rl¹,

Schiff²,

Pk³

1982

Dev Pharmacol Ther

Self Cite

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“…In neonates, the total body clearance of digoxin is lower than in adults and proportional to both gestational age and bodyweight (Collins-Nakai et al 1982). The mean plasma half-life is much longer than in adults.…”

Section: Digoxinmentioning

confidence: 93%

The Role of Therapeutic Drug Monitoring in Children

Boréus

1989

Clinical Pharmacokinetics

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Routine use of therapeutic drug monitoring in children is helpful in individualising the dosage during long term treatment (e.g. theophylline and antiepileptic drugs) and in checking against toxic accumulation of drug in neonates (e.g. digoxin, theophylline/caffeine and aminoglycoside antibiotics). In individual patients, measurements of drug concentrations in plasma may be the only way to elucidate clinically unexpected drug effects or to handle interaction phenomena.Knowledge of the pharmacokinetic and pharmacodynamic changes during development is a prerequisite for a correct interpretation of the concentration values. Unfortunately, the quantitative relation between kinetics and clinical effect is still relatively poorly known for many drugs in the paediatric age groups.Apart from the pharmacokinetic informative value, therapeutic drug monitoring also has some merit as an aid to the physician in explaining to the patient and the parents why the drug should be taken as instructed. This may improve compliance.Therapeutic drug monitoring can serve 2 purposes in paediatric care: it gives the physician information about pharmacokinetics in the patient and it can play an educational role in the interaction between the child, the parents and the doctor. This procedure therefore increases the motivation to take the drug according to instruction.

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Pharmacokinetics of HD‐MTX in infants, children, and adolescents with non‐B acute lymphoblastic leukemia

Donelli

Zucchetti

Robatto

et al. 1995

Med. Pediatr. Oncol.

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A retrospective pharmacokinetic analysis was done of methotrexate serum levels after high-dose treatment (HD-MTX, four cycles at two-week intervals of 5 g/sq.1m. over 24 h i.v.) in children with non-B acute lymphoblastic leukemia (ALL) with the specific aim of seeking differences in patients of different ages, including infants under one year. A total of 122 children (seven infants aged 3 months-1 year, 26 children aged 1-3 years, 68 children aged 3-10 years and 21 adolescents aged 10-15 years) with normal liver and renal function, receiving consolidation therapy at the Pediatric Clinic of Monza between May 1988 and April 1992, were enrolled in this study. MTX was given as an intravenous infusion in 24 h and serum concentrations were measured up to at least 72 h after the start of infusion by an enzyme immunoassay (TDX Abbot, Dallas, TX) in order to modulate folinic acid rescue. Pharmacokinetic analysis of MTX levels according to a two-compartment open model indicated that, compared to all children up to 10 years old, in adolescents older than 10 years the drug reached higher concentrations in serum and was cleared at a lower rate. Steady-state levels and AUC were from 60% higher to more than double and the total clearance of the compound, expressed either per square meter surface area or per kg body weight, in each cycle was significantly lower in adolescents > 10 years of age, sometimes being only one-third of the clearance in infants (0.2 vs. 0.6 1/h/kg and 6.6 vs. 10.7 1/h/sq.m). The relationship between each age and systemic clearance was highly significant as measured by regression analysis. Methotrexate systemic clearance progressively decreased as a function of age. Subsequent treatments did not induce changes in MTX pharmacokinetics. These data suggest that the better tolerance of HD-MTX in children may have a pharmacokinetic basis. The faster elimination of MTX in infants, who usually show the worst prognosis, suggests that full doses could be safely used in order to maximize the antileukemic effect without a high risk of toxicity.

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Total Body Digoxin Clearance and Steady-State Concentrations in Low Birth Weight Infants

Cited by 6 publications

References 12 publications

Pharmacokinetics of Digoxin in Low-Birth-Weight Infants

Pharmacokinetics of Digoxin in Low-Birth-Weight Infants

The Role of Therapeutic Drug Monitoring in Children

Pharmacokinetics of HD‐MTX in infants, children, and adolescents with non‐B acute lymphoblastic leukemia

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