Comparison Between Two Intraoperative Intravenous Loading Doses of Paracetamol on Pain After Minor Hand Surgery: Two Grams Versus One Gram

Cornesse, D.; Sénard, Marc; Hans, Grégory; Ledoux, Didier; Kirsch, Muriëlle; Hick, Gaëtane; Hallet, Claude; Joris, Jean

doi:10.1080/00015458.2010.11680670

Cited by 15 publications

(6 citation statements)

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“…loading dose of 2 g, followed by 1 g every 6 h up to 24 h, has been confirmed as safe and well tolerated in healthy volunteers [19]. Being safe and effective in nonpregnant subjects [20][21][22], the use of this i.v. loading dose of 2 g paracetamol is an accepted practice for immediate post-Caesarean delivery pain relief [23].…”

Section: Introductionmentioning

confidence: 96%

Pharmacokinetics of paracetamol and its metabolites in women at delivery and post‐partum

Kulo

Peeters

Allegaert

et al. 2013

Brit J Clinical Pharma

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AIMA recent report on intravenous (i.v.) paracetamol pharmacokinetics (PK) showed a higher total clearance in women at delivery compared with non-pregnant women. To describe the paracetamol metabolic and elimination routes involved in this increase in clearance, we performed a population PK analysis in women at delivery and post-partum in which the different pathways were considered. METHODSPopulation PK parameters using non-linear mixed effect modelling were estimated in a two-period PK study in women to whom i.v. paracetamol (2 g loading dose followed by 1 g every 6 h up to 24 h) was administered immediately following Caesarean delivery and in a subgroup of the same women to whom single 2 g i.v.loading dose was administered 10-15 weeks post-partum. RESULTSPopulation PK analysis was performed based on 255 plasma and 71 urine samples collected in 39 women at delivery and in eight of these 39 women 12 weeks post-partum. Total clearance was higher in women at delivery compared with 12th post-partum week (21.1 vs. 11.7 l h -1 ) due to higher clearances to paracetamol glucuronide (11.6 vs. 4.76 l h ). In contrast, there was no difference in clearance to paracetamol sulphate. CONCLUSIONThe increased total paracetamol clearance at delivery is caused by a disproportional increase in glucuronidation clearance and a proportional increase in clearance of unchanged paracetamol and in oxidation clearance, of which the latter may potentially limit further dose increase in this patient group. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• In adults, paracetamol is almost exclusively metabolized by the hepatic route and excreted into urine, with paracetamol glucuronide (47-62%) and paracetamol sulphate (25-36%) as the main metabolites. Between 8-10% of the paracetamol dose is oxidized by cytochrome P450 (CYP2E1) into 3-hydroxy-paracetamol and the toxic metabolite N-acetyl-p-benzoquinone-imine (NAPQI), while only 1-4% is excreted in urine as unchanged paracetamol.• Total clearance of paracetamol appears higher at Caesarean delivery compared with healthy female volunteers but it is unknown which pathways are affected. WHAT THIS STUDY ADDS• Population pharmacokinetic modelling showed a substantially higher paracetamol clearance in women at delivery compared with a subset of the same women 12 weeks post-partum.• The increase in total paracetamol clearance at delivery is due to a disproportional increase in glucuronidation clearance and a proportional increase in clearance of unchanged paracetamol and in oxidation clearance.• Compared with modelling based on metabolite fractions retrieved in urine only, population modelling based on both plasma and urine collections was of added value to gain insight into how different metabolic pathways of paracetamol contribute to changes in total clearance.

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Section: Introductionmentioning

confidence: 96%

Pharmacokinetics of paracetamol and its metabolites in women at delivery and post‐partum

Kulo

Peeters

Allegaert

et al. 2013

Brit J Clinical Pharma

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“…McNicol et al 14 recently published a systematic review on the effects of a single dose of intravenous paracetamol or propacetamol for prevention or treatment of postoperative pain in adults. Intravenous paracetamol 1 g provided approximately 4 h of effective analgesia (as judged by pain relief or opioid-sparing effects), with effectiveness diminishing after 6 h. An intraoperative loading dose of 2 g compared to 1 g, provided better analgesia in the first 24 h after the minor hand surgery, 15,16 These reports strongly suggest a link between plasma paracetamol concentrations and analgesia. In the current study, peak and trough concentrations in women following caesarean delivery were lower than in non-pregnant patients due to a larger distribution volume and higher clearance.…”

Section: Discussionmentioning

confidence: 93%

Pharmacokinetics of a loading dose of intravenous paracetamol post caesarean delivery

Kulo¹,

Velde²,

Hoon³

et al. 2012

International Journal of Obstetric Anesthesia

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“…Besides the obtained insights into the differences in the PK parameters of acetaminophen during pregnancy, information on acetaminophen PD in this population is necessary, to suggest dose adjustments. Since a strong correlation between acetaminophen concentration and analgesia is proven in healthy volunteers [ 47 , 48 ], a higher CL/F of acetaminophen in pregnant women assumes that these women experience a less analgesic effect than non-pregnant women. However, before recommending to increase the dose of acetaminophen in this population, to compensate for the higher CL/F, it has to be noted that the molar dose fractions of the toxic metabolite NAPQI might be increased in pregnant women [ 6 , 15 ].…”

Section: Discussionmentioning

confidence: 99%

Modelling Tools to Characterize Acetaminophen Pharmacokinetics in the Pregnant Population

et al. 2021

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This review describes acetaminophen pharmacokinetics (PK) throughout pregnancy, as analyzed by three methods (non-compartmental analyses (NCA), population PK, and physiologically based PK (PBPK) modelling). Eighteen studies using NCA were reported in the scientific literature. These studies reported an increase in the volume of distribution (3.5–60.7%) and an increase in the clearance (36.8–84.4%) of acetaminophen in pregnant women compared to non-pregnant women. Only two studies using population PK modelling as a technique were available in the literature. The largest difference in acetaminophen clearance (203%) was observed in women at delivery compared to non-pregnant women. One study using the PBPK technique was found in the literature. This study focused on the formation of metabolites, and the toxic metabolite N-acetyl-p-benzoquinone imine was the highest in the first trimester, followed by the second and third trimester, compared with non-pregnant women. In conclusion, this review gave an overview on acetaminophen PK changes in pregnancy. Also, knowledge gaps, such as fetal and placenta PK parameters, have been identified, which should be explored further before dosing adjustments can be suggested on an evidence-based basis.

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Comparison Between Two Intraoperative Intravenous Loading Doses of Paracetamol on Pain After Minor Hand Surgery: Two Grams Versus One Gram

Cited by 15 publications

References 0 publications

Pharmacokinetics of paracetamol and its metabolites in women at delivery and post‐partum

Pharmacokinetics of paracetamol and its metabolites in women at delivery and post‐partum

Pharmacokinetics of a loading dose of intravenous paracetamol post caesarean delivery

Modelling Tools to Characterize Acetaminophen Pharmacokinetics in the Pregnant Population

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