TY - JOUR
T1 - Modelling tools to characterize acetaminophen pharmacokinetics in the pregnant population
AU - Brookhuis, Sofie A.M.
AU - Allegaert, Karel
AU - Hanff, Lidwien M.
AU - Lub-De Hooge, Marjolijn N.
AU - Dallmann, André
AU - Mian, Paola
N1 - Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/8/20
Y1 - 2021/8/20
N2 - 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 liter-ature. 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 lit-erature. 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 lit-erature. 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 tri-mester, 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 param-eters, have been identified, which should be explored further before dosing adjustments can be sug-gested on an evidence-based basis.
AB - 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 liter-ature. 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 lit-erature. 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 lit-erature. 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 tri-mester, 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 param-eters, have been identified, which should be explored further before dosing adjustments can be sug-gested on an evidence-based basis.
UR - http://www.scopus.com/inward/record.url?scp=85113477595&partnerID=8YFLogxK
U2 - 10.3390/pharmaceutics13081302
DO - 10.3390/pharmaceutics13081302
M3 - Review article
C2 - 34452263
AN - SCOPUS:85113477595
SN - 1999-4923
VL - 13
JO - Pharmaceutics
JF - Pharmaceutics
IS - 8
M1 - 1302
ER -