Publications of all kind based on the Open Systems Pharmacology Suite
15
stars
2
forks
source link
Development of a Generic Physiologically Based Pharmacokinetic Model for Lactation and Prediction of Maternal and Infant Exposure to Ondansetron via Breast Milk #346
Job, K. M., Dallmann, A., Parry, S., Saade, G., Haas, D. M., Hughes, B., Berens, P., Chen, J. Y., Fu, C., Humphrey, K., Hornik, C., Balevic, S., Zimmerman, K., & Watt, K. Development of a Generic Physiologically Based Pharmacokinetic Model for Lactation and Prediction of Maternal and Infant Exposure to Ondansetron via Breast Milk. Clin Pharmacol Ther. 2022, Jan 25. doi: 10.1002/cpt.2530. Online ahead of print.https://pubmed.ncbi.nlm.nih.gov/35076931/
Abstract
Ondansetron is commonly used in breastfeeding mothers to treat nausea and vomiting. There is limited information in humans regarding safety of ondansetron exposure to nursing infants and no adequate study looking at ondansetron pharmacokinetics during lactation. We developed a generic physiologically based pharmacokinetic lactation model for small molecule drugs and applied this model to predict ondansetron transfer into breast milk and characterize infant exposure. Drug-specific model inputs were parameterized using data from the literature. Population-specific inputs were derived from a previously conducted systematic literature review of anatomic and physiologic changes in postpartum women. Model predictions were evaluated using ondansetron plasma and breast milk concentration data collected prospectively from 78 women in the Commonly Used Drugs During Lactation and infant Exposure study. The final model predicted breast milk and plasma exposures following a single 4 mg dose of intravenous ondansetron in 1000 simulated women who were two days postpartum. Model predictions showed good agreement with observed data. Breast milk MPE was 18.4% and MAPE was 53.0%. Plasma MPE was 32.5% and MAPE was 43.2%. The model-predicted daily and relative infant doses were 0.004 mg/kg/day and 3.0%, respectively. This model adequately predicted ondansetron passage into breast milk. The calculated low relative infant dose indicates that mothers receiving ondansetron can safely breastfeed. The model building blocks and population database are open-source and can be adapted to other drugs.
Keywords: lactation; ondansetron; physiological based pharmacokinetic model; postpartum.
AndreDlm
commented
2 years ago
Job, K. M., Dallmann, A., Parry, S., Saade, G., Haas, D. M., Hughes, B., Berens, P., Chen, J. Y., Fu, C., Humphrey, K., Hornik, C., Balevic, S., Zimmerman, K., & Watt, K. Development of a Generic Physiologically Based Pharmacokinetic Model for Lactation and Prediction of Maternal and Infant Exposure to Ondansetron via Breast Milk. Clin Pharmacol Ther. 2022, Jan 25. doi: 10.1002/cpt.2530. Online ahead of print. https://pubmed.ncbi.nlm.nih.gov/35076931/
Abstract Ondansetron is commonly used in breastfeeding mothers to treat nausea and vomiting. There is limited information in humans regarding safety of ondansetron exposure to nursing infants and no adequate study looking at ondansetron pharmacokinetics during lactation. We developed a generic physiologically based pharmacokinetic lactation model for small molecule drugs and applied this model to predict ondansetron transfer into breast milk and characterize infant exposure. Drug-specific model inputs were parameterized using data from the literature. Population-specific inputs were derived from a previously conducted systematic literature review of anatomic and physiologic changes in postpartum women. Model predictions were evaluated using ondansetron plasma and breast milk concentration data collected prospectively from 78 women in the Commonly Used Drugs During Lactation and infant Exposure study. The final model predicted breast milk and plasma exposures following a single 4 mg dose of intravenous ondansetron in 1000 simulated women who were two days postpartum. Model predictions showed good agreement with observed data. Breast milk MPE was 18.4% and MAPE was 53.0%. Plasma MPE was 32.5% and MAPE was 43.2%. The model-predicted daily and relative infant doses were 0.004 mg/kg/day and 3.0%, respectively. This model adequately predicted ondansetron passage into breast milk. The calculated low relative infant dose indicates that mothers receiving ondansetron can safely breastfeed. The model building blocks and population database are open-source and can be adapted to other drugs.
Keywords: lactation; ondansetron; physiological based pharmacokinetic model; postpartum.