Predicting Maternal and Infant Tetrahydrocannabinol Exposure in Lactating Cannabis Users: A Physiologically Based Pharmacokinetic Modeling Approach

• Main Authors: Babajide Shenkoya (Author), Venkata Yellepeddi (Author), Katrina Mark (Author), Mathangi Gopalakrishnan (Author)
• Format: Book
• Published: MDPI AG, 2023-10-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

A knowledge gap exists in infant tetrahydrocannabinol (THC) data to guide breastfeeding recommendations for mothers who use cannabis. In the present study, a paired lactation and infant physiologically based pharmacokinetic (PBPK) model was developed and verified. The verified model was used to simulate one hundred virtual lactating mothers (mean age: 28 years, body weight: 78 kg) who smoked 0.32 g of cannabis containing 14.14% THC, either once or multiple times. The simulated breastfeeding conditions included one-hour post smoking and subsequently every three hours. The mean peak concentration (C_max) and area under the concentration-time curve (AUC_{(0-24 h)}) for breastmilk were higher than in plasma (C_max: 155 vs. 69.9 ng/mL; AUC_{(0-24 h)}: 924.9 vs. 273.4 ng·hr/mL) with a milk-to-plasma AUC ratio of 3.3. The predicted relative infant dose ranged from 0.34% to 0.88% for infants consuming THC-containing breastmilk between birth and 12 months. However, the mother-to-infant plasma AUC_{(0-24 h)} ratio increased up to three-fold (3.4-3.6) with increased maternal cannabis smoking up to six times. Our study demonstrated the successful development and application of a lactation and infant PBPK model for exploring THC exposure in infants, and the results can potentially inform breastfeeding recommendations.

Item Description

10.3390/pharmaceutics15102467
1999-4923