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Physiologically‐bas...
Physiologically‐based pharmacokinetic model to predict doxorubicin and paclitaxel exposure in infants through breast milk
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- Damoiseaux, David (författare)
- Department of Pharmacy and Pharmacology The Netherlands Cancer Institute Amsterdam The Netherlands
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- Amant, Frédéric (författare)
- Department of Gynecology The Netherlands Cancer Institute Amsterdam The Netherlands;Gynecologic Oncology UZ Leuven Leuven Belgium
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- Beijnen, Jos H. (författare)
- Department of Pharmacy and Pharmacology The Netherlands Cancer Institute Amsterdam The Netherlands;Utrecht Institute of Pharmaceutical Sciences Utrecht University Utrecht The Netherlands
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- Barnett, Shelby (författare)
- Newcastle University Centre for Cancer Newcastle University Newcastle upon Tyne UK
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- Veal, Gareth J. (författare)
- Newcastle University Centre for Cancer Newcastle University Newcastle upon Tyne UK
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- Huitema, Alwin D. R. (författare)
- Department of Pharmacy and Pharmacology The Netherlands Cancer Institute Amsterdam The Netherlands;Department of Pharmacology Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands;Department of Clinical Pharmacy, University Medical Center Utrecht Utrecht University Utrecht The Netherlands
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- Dorlo, Thomas P. C., 1983- (författare)
- Uppsala universitet,Institutionen för farmaci,Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
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(creator_code:org_t)
- John Wiley & Sons, 2023
- 2023
- Engelska.
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Ingår i: CPT. - : John Wiley & Sons. - 2163-8306. ; 12:12, s. 1931-1944
- Relaterad länk:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Limited information is available concerning infant exposure and safety when breastfed by mothers receiving chemotherapy. Whereas defining distribution to breast milk is important to infer drug exposure, infant pharmacokinetics also determine to what extent the infant will be exposed to potential toxic effects. We aimed to assess the impact of chemotherapy containing breast milk on infants by predicting systemic and local (intestinal) exposure of paclitaxel and doxorubicin in infants through breast milk using a physiologically-based pharmacokinetic (PBPK) approach. Whole-body PBPK models of i.v. paclitaxel and doxorubicin were extended from the literature, with an oral absorption component to enable predictions in infants receiving paclitaxel or doxorubicin-containing breast milk. For safety considerations, worst-case scenarios were explored. Finally, paclitaxel and doxorubicin exposures in plasma and intestinal tissue of infants following feeding of breast milk from paclitaxel- or doxorubicin-treated mothers were simulated and breast milk discarding strategies were evaluated. The upper 95th percentile of the predicted peak concentrations in peripheral venous blood were 3.48 and 0.74 nM (0.4%–1.7% and 0.1%–1.8% of on-treatment) for paclitaxel and doxorubicin, respectively. Intestinal exposure reached peak concentrations of 1.0 and 140 μM for paclitaxel and doxorubicin, respectively. Discarding breast milk for the first 3 days after maternal chemotherapy administration reduced systemic and tissue exposures even further, to over 90% and 80% for paclitaxel and doxorubicin, respectively. PBPK simulations of chemotherapy exposure in infants after breastfeeding with chemotherapy containing breast milk suggest that particularly local gastrointestinal adverse events should be monitored, whereas systemic adverse events are not expected.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
Nyckelord
- Farmaceutisk vetenskap
- Pharmaceutical Science
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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