Excretion of paracetamol in human breast milk

Bitzén, Per-Olof; Gustafsson, Bàrbro; Jostell, K.‐G.; Melander, Arne; Wåhlin-Boll, E

doi:10.1007/bf00607148

Cited by 68 publications

(24 citation statements)

References 4 publications

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“…(c) (Berlin et al, 1980;Bitzen et al, 1981;Findlay et al, 1981). The amount of paracetamol received by the suckling infant in a feed may be calculated as a percentage of the weight-adjusted maternal dose received in this study or as a percentage of the lowest recommended infant single dose.…”

Section: Resultsmentioning

confidence: 99%

Passage of paracetamol into breast milk and its subsequent metabolism by the neonate.

Notarianni

Oldham

Bennett

1987

Brit J Clinical Pharma

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1 Paracetamol was administered to nursing mothers. The drug passed rapidly into milk and the milk:plasma concentration ratio was approximately unity. 2 The estimated maximum dose to the neonate was 1.85% of the weight-adjusted maternal oral dose of paracetamol 1.0 g. Recovery of paracetamol was greater from the breast from which samples were taken frequently than from the breast which was sampled only once. 3 Paracetamol, its glucuronide, sulphate, cysteine and mercapturate conjugates were found in the urine of the neonates although only the parent drug was detected in breast milk.4 The neonates excreted significantly greater proportions of unchanged paracetamol (P < 0.01) and significantly lesser proportions of paracetamol sulphate (P < 0.001) than did healthy volunteers aged 11-80 years who received a therapeutic dose of paracetamol. 5 The findings are compatible with a deficiency of sulphate conjugation by the neonate.Keywords paracetamol neonate metabolism breast milk biotransformation

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Section: Resultsmentioning

confidence: 99%

Passage of paracetamol into breast milk and its subsequent metabolism by the neonate.

Notarianni

Oldham

Bennett

1987

Brit J Clinical Pharma

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“…During pregnancy, analgesics are generally taken to relieve migraine, pain, and fever, but are also used in inflammatory conditions and are frequently used during preterm labor15678. These medications are known to cross the placenta and to be present in meconium, neonatal urine, and in breast milk, indicating painkiller transmission from the mother to the fetus and to neonates9101112131415. Attention has recently been focused on the associations between analgesic use during the second and third trimesters of pregnancy and a number of unwanted effects in children.…”

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confidence: 99%

Ibuprofen results in alterations of human fetal testis development

Maamar

Lesné

Hennig

et al. 2017

Sci Rep

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Among pregnant women ibuprofen is one of the most frequently used pharmaceutical compounds with up to 28% reporting use. Regardless of this, it remains unknown whether ibuprofen could act as an endocrine disruptor as reported for fellow analgesics paracetamol and aspirin. To investigate this, we exposed human fetal testes (7–17 gestational weeks (GW)) to ibuprofen using ex vivo culture and xenograft systems. Ibuprofen suppressed testosterone and Leydig cell hormone INSL3 during culture of 8–9 GW fetal testes with concomitant reduction in expression of the steroidogenic enzymes CYP11A1, CYP17A1 and HSD17B3, and of INSL3. Testosterone was not suppressed in testes from fetuses younger than 8 GW, older than 10–12 GW, or in second trimester xenografted testes (14–17 GW). Ex vivo, ibuprofen also affected Sertoli cell by suppressing AMH production and mRNA expression of AMH, SOX9, DHH, and COL2A1. While PGE2 production was suppressed by ibuprofen, PGD2 production was not. Germ cell transcripts POU5F1, TFAP2C, LIN28A, ALPP and KIT were also reduced by ibuprofen. We conclude that, at concentrations relevant to human exposure and within a particular narrow ‘early window’ of sensitivity within first trimester, ibuprofen causes direct endocrine disturbances in the human fetal testis and alteration of the germ cell biology.

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“…Taking into account the problem of dosing, we relied mainly on our earlier experience and data from pharmacokinetic studies in humans (Berlin et al, 1980; Bitzen et al, 1981; Blecharz‐Klin et al, 2013; Blecharz‐Klin et al, 2014; Blecharz‐Klin et al, 2015; Notarianni et al, 1987). Our intention was to demonstrate barely noticeable changes occurring in the central nervous system.…”

Section: Discussionmentioning

confidence: 99%

Effect of prenatal and early life paracetamol exposure on the level of neurotransmitters in rats—Focus on the spinal cord

Blecharz-Klin

Joniec-Maciejak

Jawna

et al. 2015

Intl J of Devlp Neuroscience

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The present study has examined the influence of the prenatal and early life administration of paracetamol on the level of neurotransmitters in the spinal cord of rat pups. The effect of the drug was evaluated in 2-month old Wistar male rats exposed to paracetamol in doses of 5 (P5, n=9) or 15 mg/kg (P15, n=9) p.o. during the prenatal period and after birth until the completion of the second month of life. A parallel control group received tap water (Con, n=9). In this study we have determined the level of monoamines, their metabolites and amino acids in the spinal cord of rats using high performance liquid chromatography (HPLC) in the second month of life. The present experiment demonstrates the action of paracetamol at the molecular level associated with significant modulation of neurotransmission in the spinal cord related to dopaminergic and noradrenergic systems. Simultaneously, paracetamol administration increases the content of an aspartic and glutamic acids in the spinal cord at a critical time during development.

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Excretion of paracetamol in human breast milk

Cited by 68 publications

References 4 publications

Passage of paracetamol into breast milk and its subsequent metabolism by the neonate.

Passage of paracetamol into breast milk and its subsequent metabolism by the neonate.

Ibuprofen results in alterations of human fetal testis development

Effect of prenatal and early life paracetamol exposure on the level of neurotransmitters in rats—Focus on the spinal cord

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