Cannabidiol Exposure Through Maternal Marijuana Use: Predictions in Breastfed Infants.
Journal
Clinical pharmacokinetics
ISSN: 1179-1926
Titre abrégé: Clin Pharmacokinet
Pays: Switzerland
ID NLM: 7606849
Informations de publication
Date de publication:
11 2023
11 2023
Historique:
accepted:
04
09
2023
medline:
23
10
2023
pubmed:
22
9
2023
entrez:
22
9
2023
Statut:
ppublish
Résumé
Knowledge about exposure to cannabidiol (CBD) in breastfed infants can provide an improved understanding of potential risk. The aim was to predict CBD exposure in breastfed infants from mothers taking CBD and CBD-containing products. Cannabidiol concentrations in milk previously attained from data collected through an existing human milk research biorepository were used to simulate infant doses and identify subgroups. A developed pediatric physiologically based pharmacokinetic model produced virtual breastfed infants administered the simulated CBD doses. Predicted breastfed infant exposures and upper area under the curve ratios were compared to the lowest therapeutic dose for approved indications in children. The existing human milk research biorepository contained 200 samples from 181 unique breastfeeding mothers for whom self-reported administration data and CBD concentrations had previously been measured. Samples that were above the lower limit of quantification with only one maternal administration type revealed that administration type, i.e., joint/blunt or edible versus oil or pipe, resulted in significantly different subgroups in terms of milk concentrations. Resulting simulated infant doses (ng/kg) were described by lognormal distributions with geometric means and geometric standard deviations: 0.61 ± 2.41 all concentrations, 0.10 ± 0.37 joint/blunt or edible, and 2.23 ± 8.15 oil or pipe. Doses administered to breastfed infants had exposures magnitudes lower than exposures in children aged 4-11 years administered the lowest therapeutic dose for approved indications, and low upper area under the curve ratios. Based on real-world use, breastfeeding infants are predicted to receive very small exposures of CBD through milk. Studies examining adverse reactions will provide further insight into potential risk.
Sections du résumé
BACKGROUND AND OBJECTIVE
Knowledge about exposure to cannabidiol (CBD) in breastfed infants can provide an improved understanding of potential risk. The aim was to predict CBD exposure in breastfed infants from mothers taking CBD and CBD-containing products.
METHODS
Cannabidiol concentrations in milk previously attained from data collected through an existing human milk research biorepository were used to simulate infant doses and identify subgroups. A developed pediatric physiologically based pharmacokinetic model produced virtual breastfed infants administered the simulated CBD doses. Predicted breastfed infant exposures and upper area under the curve ratios were compared to the lowest therapeutic dose for approved indications in children.
RESULTS
The existing human milk research biorepository contained 200 samples from 181 unique breastfeeding mothers for whom self-reported administration data and CBD concentrations had previously been measured. Samples that were above the lower limit of quantification with only one maternal administration type revealed that administration type, i.e., joint/blunt or edible versus oil or pipe, resulted in significantly different subgroups in terms of milk concentrations. Resulting simulated infant doses (ng/kg) were described by lognormal distributions with geometric means and geometric standard deviations: 0.61 ± 2.41 all concentrations, 0.10 ± 0.37 joint/blunt or edible, and 2.23 ± 8.15 oil or pipe. Doses administered to breastfed infants had exposures magnitudes lower than exposures in children aged 4-11 years administered the lowest therapeutic dose for approved indications, and low upper area under the curve ratios.
CONCLUSIONS
Based on real-world use, breastfeeding infants are predicted to receive very small exposures of CBD through milk. Studies examining adverse reactions will provide further insight into potential risk.
Identifiants
pubmed: 37735347
doi: 10.1007/s40262-023-01307-6
pii: 10.1007/s40262-023-01307-6
pmc: PMC10659070
mid: NIHMS1942320
doi:
Substances chimiques
Cannabidiol
19GBJ60SN5
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1611-1619Subventions
Organisme : NCATS NIH HHS
ID : UL1 TR001442
Pays : United States
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.
Références
AAPS J. 2013 Apr;15(2):455-64
pubmed: 23344790
CPT Pharmacometrics Syst Pharmacol. 2023 Mar;12(3):320-332
pubmed: 36540909
Epilepsia. 2020 Feb;61(2):267-277
pubmed: 32012251
Neurology. 2018 Apr 3;90(14):e1204-e1211
pubmed: 29540584
Drug Metab Dispos. 2009 Jul;37(7):1496-504
pubmed: 19339377
Matern Child Nutr. 2020 Apr;16(2):e12938
pubmed: 31965755
J Clin Pharmacol. 2019 Aug;59(8):1110-1119
pubmed: 30921490
CNS Drugs. 2018 Nov;32(11):1053-1067
pubmed: 30374683
Gerontologist. 1994 Aug;34(4):486-90
pubmed: 7959106
Front Psychiatry. 2020 Nov 02;11:586447
pubmed: 33240134
Pediatrics. 2018 Sep;142(3):
pubmed: 30150212
Pediatrics. 2022 Jul 1;150(1):
pubmed: 35921640
Drug Metab Dispos. 2021 Oct;49(10):882-891
pubmed: 34330718
Drug Metab Dispos. 2023 Jun;51(6):743-752
pubmed: 36972999
AAPS J. 2021 May 17;23(4):70
pubmed: 34002327
Psychopharmacology (Berl). 2022 May;239(5):1509-1519
pubmed: 35020045
Obstet Gynecol. 2017 Oct;130(4):e205-e209
pubmed: 28937574
Clin Pharmacokinet. 2018 Dec;57(12):1603-1611
pubmed: 29651785
Clin Pharmacokinet. 2020 Jun;59(6):747-755
pubmed: 31802404
CNS Drugs. 2019 Jun;33(6):593-604
pubmed: 31049885
Cannabis Cannabinoid Res. 2022 Jun;7(3):355-364
pubmed: 33998872
Epilepsy Behav. 2018 Nov;88:162-171
pubmed: 30286443