Diazepam elimination in premature and full term infants, and children

Morselli, P. L.; Principi, Nicola; Tognoni, G.; Reali, E.; Belvedere, G.; Standen, S.; Sereni, F

doi:10.1515/jpme.1973.1.2.133

Cited by 116 publications

(37 citation statements)

References 23 publications

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“…These infants were treated with phénobarbital, either after birth (two cases), or during fetal life (three cases), in the latter case the mothers were treated with this drug for various periods during gestation. In a previous paper (17) we reported the values of urinary excretion of diazepam metabolites in premature and full-term infants. The most relevant data are shown in table II.…”

Section: Recent Observations In Our Laboratorymentioning

confidence: 99%

Induction of Drug Metabolizing Enzyme Activities in the Human Fetus and in the Newborn Infant

Sereni¹,

Mandelli²,

Principi³

et al. 1973

Enzyme Protein

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Diazepam metabolism was followed in five newborns exposed to phenobarbital either during fetal life or after birth. A considerable increase of urinary metabolites and of plasma apparent K(el) was observed in comparison with newborns not exposed to the barbiturate. These findings may be considered as an indirect evidence of induction of drug metabolizing enzymes during the last part of gestation and shortly after birth. Present knowledge on liver enzyme induction in fetuses and neonates is critically reviewed.

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Section: Recent Observations In Our Laboratorymentioning

confidence: 99%

Induction of Drug Metabolizing Enzyme Activities in the Human Fetus and in the Newborn Infant

Sereni¹,

Mandelli²,

Principi³

et al. 1973

Enzyme Protein

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“…In premature infants the half-life of diazepam is considerably prolonged, whereas young children exhibit values around 18 h (38). The complete lifetime temporal pattern of the drug half-life/age relationship is therefore complex and the changes probably involve multiple causative factors.…”

mentioning

confidence: 99%

The Effects of Age and Liver Disease on the Disposition and Elimination of Diazepam in Adult Man

Klotz

Avant

Hoyumpa

et al. 1976

Survey of Anesthesiology

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“…Although samples from such an early time period had not been available in our study, it is reasonable to assume that also the free fractions of D and DD rise sharply during that time due to the close interrelation between D and DD free fractions on the one hand and FFA levels on the other (Naranjo et al, 1980a). Due to the known deficiency of the neonatal elimination capacity for D resulting in prolonged half-life for this drug (Morselli et al, 1973;Mandelli et al, 1975), the sharply increased free fractions may not necessarily lead to decreased total drug levels through increased total clearance. Elevated free concentrations of D may therefore persist for a prolonged time (Figure 1).…”

Section: Discussionmentioning

confidence: 95%

Decreased serum protein binding of diazepam and its major metabolite in the neonate during the first postnatal week relate to increased free fatty acid levels.

Nau¹,

Luck²,

Kuhnz³

1984

Brit J Clinical Pharma

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The protein binding of diazepam (D) and its major active metabolite N-desmethyl diazepam (DD) was investigated in vitro in the serum of 14 mothers at birth, 21 foetuses at birth, in 100 neonates between 1 and 11 days of age and in 16 control subjects. The free (unbound) fractions of D and DD in the foetus were similar to those in the controls, but lower than those in the mothers. During the first day of life the free fractions of D and DD doubled in the neonates and subsequently declined slowly to reach near control levels at 1 week of age.The sharp increase and slow decrease of the free fractions of D and DD during the first postnatal week was closely paralleled by sharply increasing and decreasing free fatty acid (FFA) concentrations. Bilirubin and albumin levels were of lower importance in regard to the protein binding of D and DD.These results indicate that the greatly increased FFA levels shortly after birth result in increased free fractions of D and DD. Because of the known immaturity of the neonatal hepatic elimination capacity, these elevated free fractions may result in elevated free concentrations of the two compounds, which may help to explain the adverse effects observed clinically in some D-exposed neonates.

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Diazepam elimination in premature and full term infants, and children

Cited by 116 publications

References 23 publications

Induction of Drug Metabolizing Enzyme Activities in the Human Fetus and in the Newborn Infant

Induction of Drug Metabolizing Enzyme Activities in the Human Fetus and in the Newborn Infant

The Effects of Age and Liver Disease on the Disposition and Elimination of Diazepam in Adult Man

Decreased serum protein binding of diazepam and its major metabolite in the neonate during the first postnatal week relate to increased free fatty acid levels.

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