Blood Levels of D1azepam in Infants of Two Mothers Given Large Doses of Diazepam During Labour

McCarthy, Gillian; O'Connell, Bridget; Robinson, Ann E.

doi:10.1111/j.1471-0528.1973.tb11206.x

Cited by 36 publications

(6 citation statements)

References 4 publications

(1 reference statement)

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“…The disadvantage of diazepam is that heavy prolonged sedation of the woman incrcases the risk of aspiration pneumonia and other respiratory problems which contribute to maternal mortality and morbidity (Crowther 1986;Slater et al 1987). Large doses of diarepam are often required and these can lead to neonatal respiratory depression, hypothermia, hypotonia, and poor sucking (McCarthy et al 1973;Cree et al 1973).…”

mentioning

confidence: 99%

Magnesium sulphate versus diazepam in the management of eclampsia: A randomized controlled trial

Crowther¹

1990

Intl J Gynecology & Obste

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confidence: 99%

Magnesium sulphate versus diazepam in the management of eclampsia: A randomized controlled trial

Crowther¹

1990

Intl J Gynecology & Obste

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“…In a majority of previous studies diazepam umbilical cord plasma concentrations exceeded maternal concentrations [ 23 - 25 ], although feto: maternal ratios below 1 have also been reported [ 26 ]. Diazepam is highly liposoluble and crosses placenta by passive diffusion via transcellular route [ 27 , 28 ] thus diazepam transfer depends on properties of the placenta and is in a function of multiple factors such as placental blood flow, protein binding, lipid solubility and ionization constant (pKa).…”

Section: Discussionmentioning

confidence: 99%

Diabetes and hypertension increase the placental and transcellular permeation of the lipophilic drug diazepam in pregnant women

Lalić-Popović

Paunkovic

Grujić

et al. 2013

BMC Pregnancy Childbirth

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BackgroundPrevious studies carried out in our laboratories have demonstrated impaired drug permeation in diabetic animals. In this study the permeation of diazepam (after a single dose of 5 mg/day, administered intramuscularly) will be investigated in diabetic and hypertensive pregnant women.MethodsA total 75 pregnant women were divided into three groups: group 1 (healthy control, n = 31), group 2 (diabetic, n = 14) and group 3 (hypertensive, n = 30). Two sets of diazepam plasma concentrations were collected and measured (after the administration of the same dose of diazepam), before, during and after delivery. The first set of blood samples was taken from the mother (maternal venous plasma). The second set of samples was taken from the fetus (fetal umbilical venous and arterial plasma). In order to assess the effect of diabetes and hypertension on diazepam placental-permeation, the ratios of fetal to maternal blood concentrations were determined. Differences were considered statistically significant if p ≤ 0.05.ResultsThe diabetes and hypertension groups have 2-fold increase in the fetal umbilical-venous concentrations, compared to the maternal venous concentrations. Feto: maternal plasma-concentrations ratios were higher in diabetes (2.01 ± 1.10) and hypertension (2.26 ± 1.23) groups compared with control (1.30 ± 0.48) while, there was no difference in ratios between the diabetes and hypertension groups. Umbilical-cord arterial: venous ratios (within each group) were similar among all groups (control: 0.97 ± 0.32; hypertension: 1.08 ± 0.60 and diabetes: 1.02 ± 0.77).ConclusionsOn line with our previous findings which demonstrate disturbed transcellular trafficking of lipophilic drugs in diabetes, this study shows significant increase in diazepam placental-permeation in diabetic and hypertensive pregnant women suggesting poor transcellular control of drug permeation and flux, and bigger exposure of the fetus to drug-placental transport.

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“…HIGH doses of diazepam (more than 30 mg) given by intramuscular or intravenous injection to mothers during labour have been reported to cause deleterious effects on the newborn infants (Cree et al, 1973;McCarthy et al, 1973). The dose, the time available for drug transfer to the fetus, the injection-delivery interval, and the mode of administration have all been shown to influence the fetal exposure to the drug (Goldstein et al, 1974).…”

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Diazepam as an Induction Agent for Caesarean Section: A Clinical and Pharmacokinetic Study of Fetal Drug Exposure

Haram¹,

Bakke

1980

BJOG

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Summary The transplacental passage and clinical effects of diazepam have been studied in 30 patients undergoing elective Caesarean section. General anaesthesia was induced with diazepam (20 mg) and maintained with nitrous oxide/oxygen. The time from completed intravenous injection of diazepam to clamping of the umbilical cord varied from 184 to 810 seconds. The concentrations of diazepam in serial blood samples obtained from the mothers, the umbilical cord and the newborn infants demonstrated that the transplacental passage of the drug was rapid and there was evidence that the distribution of the drug between the mother and the fetus came close to equilibrium. There was no consistent relation between Apgar scores and the extent of the fetal exposure to diazepam.

show abstract

Blood Levels of D1azepam in Infants of Two Mothers Given Large Doses of Diazepam During Labour

Cited by 36 publications

References 4 publications

Magnesium sulphate versus diazepam in the management of eclampsia: A randomized controlled trial

Magnesium sulphate versus diazepam in the management of eclampsia: A randomized controlled trial

Diabetes and hypertension increase the placental and transcellular permeation of the lipophilic drug diazepam in pregnant women

Diazepam as an Induction Agent for Caesarean Section: A Clinical and Pharmacokinetic Study of Fetal Drug Exposure

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