De complexe interactie tussen paracetamol en ethanol

Merel van der Meulen; Kris L.L. Movig; Ruben J. Schuinder; Joost B. Masselink; Paola Mian

De complexe interactie tussen paracetamol en ethanol

Translated title of the contribution: The complex interaction between paracetamol and ethanol

Merel van der Meulen^*
, Kris L.L. Movig
, Ruben J. Schuinder
, Joost B. Masselink
, Paola Mian^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Introduction: This case report describes a disturbed paracetamol (PCM) clearance in a patient with a history of chronic ethanol abuse and triggered us to elaborate on the possible effects of ethanol on PCM induced hepatotoxicity and the mechanism of the interaction between PCM and ethanol in both animals and humans.

Description: A 54-year old female presented with a PCM (approximately 250 mg/kg) and ethanol (1 litre of whisky) related autointoxication. She received intravenous N-acetylcysteine. Four and a half hours after ingestion of PCM and ethanol, blood levels of PCM and ethanol were 90.2 mg/L and 4.2 g/L, respectively, whereas liver values (aspartate aminotransferase [ASAT], alanine aminotransferase [ALAT], gamma-glutamyltransferase [GGTJ, alkaline phosphatase [AP]) were normal. After 10 hours, PCM blood level had decreased to 36.9 mg/L with a prolonged half-life (t1/2) of 4.3 hours; liver values remained normal. After 17 hours, t_1/2had decreased to 2.4 hours and PCM blood level to 5 mg/L.

Discussion and conclusion: Acute ethanol use seems to protect against PCM induced hepatotoxicity in animals and humans by inhibiting cytochrome P450 (CYP) enzymes. Chronic ethanol use, on the other hand, seems to increase the risk on PCM induced hepatotoxicity in both. In animals, through induction of CYP2E1 whereas in humans depletion of glutathione seems to play a role. In this case report, disturbed PCM clearance could be caused by a simultaneous intake of an acute dose ethanol and PCM. One of the hypotheses for causing an increased t1/2 of PCM could be the partly inhibited metabolism of PCM by CYP2E1 through ethanol. Whereas after total clearance of ethanol, PCM was no longer inhibited and metabolism was restored. It has to be noted that this cannot be the complete explanation, as the CYP2E1-pathway is a minor route within the PCM metabolism. However, the contribution of the CYP2E1-route to the metabolism of PCM increases after an overdose, due to saturation of the glucuronide and sulfation route.

Translated title of the contribution	The complex interaction between paracetamol and ethanol
Original language	Dutch
Pages (from-to)	29-35
Number of pages	7
Journal	Pharmaceutisch Weekblad
Volume	157
Issue number	6
Publication status	Published - 11-Feb-2022
Externally published	Yes

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title = "De complexe interactie tussen paracetamol en ethanol",

abstract = "Introduction: This case report describes a disturbed paracetamol (PCM) clearance in a patient with a history of chronic ethanol abuse and triggered us to elaborate on the possible effects of ethanol on PCM induced hepatotoxicity and the mechanism of the interaction between PCM and ethanol in both animals and humans.Description: A 54-year old female presented with a PCM (approximately 250 mg/kg) and ethanol (1 litre of whisky) related autointoxication. She received intravenous N-acetylcysteine. Four and a half hours after ingestion of PCM and ethanol, blood levels of PCM and ethanol were 90.2 mg/L and 4.2 g/L, respectively, whereas liver values (aspartate aminotransferase [ASAT], alanine aminotransferase [ALAT], gamma-glutamyltransferase [GGTJ, alkaline phosphatase [AP]) were normal. After 10 hours, PCM blood level had decreased to 36.9 mg/L with a prolonged half-life (t1/2) of 4.3 hours; liver values remained normal. After 17 hours, t1/2had decreased to 2.4 hours and PCM blood level to 5 mg/L.Discussion and conclusion: Acute ethanol use seems to protect against PCM induced hepatotoxicity in animals and humans by inhibiting cytochrome P450 (CYP) enzymes. Chronic ethanol use, on the other hand, seems to increase the risk on PCM induced hepatotoxicity in both. In animals, through induction of CYP2E1 whereas in humans depletion of glutathione seems to play a role. In this case report, disturbed PCM clearance could be caused by a simultaneous intake of an acute dose ethanol and PCM. One of the hypotheses for causing an increased t1/2 of PCM could be the partly inhibited metabolism of PCM by CYP2E1 through ethanol. Whereas after total clearance of ethanol, PCM was no longer inhibited and metabolism was restored. It has to be noted that this cannot be the complete explanation, as the CYP2E1-pathway is a minor route within the PCM metabolism. However, the contribution of the CYP2E1-route to the metabolism of PCM increases after an overdose, due to saturation of the glucuronide and sulfation route.",

author = "\{van der Meulen\}, Merel and Movig, \{Kris L.L.\} and Schuinder, \{Ruben J.\} and Masselink, \{Joost B.\} and Paola Mian",

year = "2022",

month = feb,

day = "11",

language = "Dutch",

volume = "157",

pages = "29--35",

journal = "Pharmaceutisch Weekblad",

issn = "0031-6911",

publisher = "Kon. Ned. Mij. ter Bevordering der Pharmacie (KNMP)",

number = "6",

}

TY - JOUR

T1 - De complexe interactie tussen paracetamol en ethanol

AU - van der Meulen, Merel

AU - Movig, Kris L.L.

AU - Schuinder, Ruben J.

AU - Masselink, Joost B.

AU - Mian, Paola

PY - 2022/2/11

Y1 - 2022/2/11

N2 - Introduction: This case report describes a disturbed paracetamol (PCM) clearance in a patient with a history of chronic ethanol abuse and triggered us to elaborate on the possible effects of ethanol on PCM induced hepatotoxicity and the mechanism of the interaction between PCM and ethanol in both animals and humans.Description: A 54-year old female presented with a PCM (approximately 250 mg/kg) and ethanol (1 litre of whisky) related autointoxication. She received intravenous N-acetylcysteine. Four and a half hours after ingestion of PCM and ethanol, blood levels of PCM and ethanol were 90.2 mg/L and 4.2 g/L, respectively, whereas liver values (aspartate aminotransferase [ASAT], alanine aminotransferase [ALAT], gamma-glutamyltransferase [GGTJ, alkaline phosphatase [AP]) were normal. After 10 hours, PCM blood level had decreased to 36.9 mg/L with a prolonged half-life (t1/2) of 4.3 hours; liver values remained normal. After 17 hours, t1/2had decreased to 2.4 hours and PCM blood level to 5 mg/L.Discussion and conclusion: Acute ethanol use seems to protect against PCM induced hepatotoxicity in animals and humans by inhibiting cytochrome P450 (CYP) enzymes. Chronic ethanol use, on the other hand, seems to increase the risk on PCM induced hepatotoxicity in both. In animals, through induction of CYP2E1 whereas in humans depletion of glutathione seems to play a role. In this case report, disturbed PCM clearance could be caused by a simultaneous intake of an acute dose ethanol and PCM. One of the hypotheses for causing an increased t1/2 of PCM could be the partly inhibited metabolism of PCM by CYP2E1 through ethanol. Whereas after total clearance of ethanol, PCM was no longer inhibited and metabolism was restored. It has to be noted that this cannot be the complete explanation, as the CYP2E1-pathway is a minor route within the PCM metabolism. However, the contribution of the CYP2E1-route to the metabolism of PCM increases after an overdose, due to saturation of the glucuronide and sulfation route.

AB - Introduction: This case report describes a disturbed paracetamol (PCM) clearance in a patient with a history of chronic ethanol abuse and triggered us to elaborate on the possible effects of ethanol on PCM induced hepatotoxicity and the mechanism of the interaction between PCM and ethanol in both animals and humans.Description: A 54-year old female presented with a PCM (approximately 250 mg/kg) and ethanol (1 litre of whisky) related autointoxication. She received intravenous N-acetylcysteine. Four and a half hours after ingestion of PCM and ethanol, blood levels of PCM and ethanol were 90.2 mg/L and 4.2 g/L, respectively, whereas liver values (aspartate aminotransferase [ASAT], alanine aminotransferase [ALAT], gamma-glutamyltransferase [GGTJ, alkaline phosphatase [AP]) were normal. After 10 hours, PCM blood level had decreased to 36.9 mg/L with a prolonged half-life (t1/2) of 4.3 hours; liver values remained normal. After 17 hours, t1/2had decreased to 2.4 hours and PCM blood level to 5 mg/L.Discussion and conclusion: Acute ethanol use seems to protect against PCM induced hepatotoxicity in animals and humans by inhibiting cytochrome P450 (CYP) enzymes. Chronic ethanol use, on the other hand, seems to increase the risk on PCM induced hepatotoxicity in both. In animals, through induction of CYP2E1 whereas in humans depletion of glutathione seems to play a role. In this case report, disturbed PCM clearance could be caused by a simultaneous intake of an acute dose ethanol and PCM. One of the hypotheses for causing an increased t1/2 of PCM could be the partly inhibited metabolism of PCM by CYP2E1 through ethanol. Whereas after total clearance of ethanol, PCM was no longer inhibited and metabolism was restored. It has to be noted that this cannot be the complete explanation, as the CYP2E1-pathway is a minor route within the PCM metabolism. However, the contribution of the CYP2E1-route to the metabolism of PCM increases after an overdose, due to saturation of the glucuronide and sulfation route.

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UR - https://www.knmp.nl/resolveuid/1f5d516395fc46a99024fda69e109560

M3 - Article

AN - SCOPUS:85131647005

SN - 0031-6911

VL - 157

SP - 29

EP - 35

JO - Pharmaceutisch Weekblad

JF - Pharmaceutisch Weekblad

IS - 6

ER -

De complexe interactie tussen paracetamol en ethanol

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