Etienne Weisskopf1, Monia Guidi1,2, Céline J Fischer3, Myriam Bickle Graz3, Etienne Beaufils4, Kim An Nguyen5,6, Mathilde Morisod Harari7, Sylvie Rouiller8, Sophie Rothenburger9, Pascal Gaucherand4, Behrouz Kassai-Koupai6, Cristina Borradori Tolsa10, Manuella Epiney11, Jean-François Tolsa3, Yvan Vial12, Jean-Michel Hascoët13, Olivier Claris5,14, Chin B Eap1,15, Alice Panchaud1,16, Chantal Csajka1. 1. Center for Research and Innovation in Clinical Pharmaceutical Sciences, Institute of Pharmaceutical Sciences of Western Switzerland, Lausanne University Hospital and University of Lausanne, University of Geneva, Switzerland. 2. Service of Clinical Pharmacology, Lausanne University Hospital, Lausanne, Switzerland. 3. Clinic of Neonatology, Lausanne University Hospital, Lausanne, Switzerland. 4. Department of Obstetrics, Hospices Civils de Lyon, Lyon, France. 5. Department of Neonatology, Hospices Civils de Lyon, Lyon, France. 6. Department of Pharmacotoxicology, CHU Lyon, Lyon, France. 7. Division of Child and Adolescent Psychiatry, Lausanne University Hospital, Lausanne, Switzerland. 8. Service of Gynecology and Obstetrics, Ensemble hospitalier de la Côte, Morges, Switzerland. 9. Department of Obstetrics and Gynecology, Maternité, CHRU Nancy, Nancy, France. 10. Division of Child Development and Growth, Geneva University Hospital, Geneva, Switzerland. 11. Department of Gynecology and Obstetrics, Geneva University Hospital, Geneva, Switzerland. 12. Department of Gynecology, Obstetrics and Genetics, Lausanne University Hospital, Lausanne, Switzerland. 13. Department of Neonatology, Maternité Régionale, Université de Lorraine, Nancy, France. 14. Claude Bernard University, P2S 4129, Lyon, France. 15. Unit of Pharmacogenetics and Clinical Psychopharmacology, Department of Psychiatry, Lausanne University Hospital, Lausanne, Switzerland. 16. Pharmacy Service, Lausanne University Hospital, Lausanne, Switzerland.
Abstract
BACKGROUND AND OBJECTIVES: Escitalopram (SCIT) is frequently prescribed to breastfeeding women. Available information on SCIT excretion into breast milk is based on heterogeneous and incomplete data. A population pharmacokinetic model that aimed to better characterize maternal and infant exposure to SCIT and its metabolite was developed. METHODS: The study population was composed of women treated by SCIT or racemic citalopram and enrolled in the multicenter prospective cohort study SSRI-Breast Milk study (ClinicalTrial.gov NCT01796132). A joint structural model was first built for SCIT and S-desmethylcitalopram (SDCIT) in plasma using NONMEM and the milk-to-plasma ratio (MPR) was estimated by adding the drug breast milk concentrations. The effect of different influential covariates was tested and the average drug exposure with variability through breastfeeding was predicted under various conditions by simulation. RESULTS: The study enrolled 33 patients treated with SCIT or racemic citalopram who provided 80 blood and 104 milk samples. Mean MPR for both parent drug and metabolite was 1.9. Increased milk fat content was significantly associated with an increased drug transfer into breast milk (+28% for SCIT and +18% for SDCIT when fat amount doubles from 3.1 to 6.2 g/100 mL). Simulations suggested that an exclusively breastfed infant would ingest daily through breast milk 3.3% of the weight-adjusted maternal SCIT dose on average. CONCLUSION: The moderate between-subject variability in milk concentration of SCIT and the limited exposure to escitalopram through breast milk observed provide reassurance for treated mothers of breastfed healthy infants.
BACKGROUND AND OBJECTIVES:Escitalopram (SCIT) is frequently prescribed to breastfeeding women. Available information on SCIT excretion into breast milk is based on heterogeneous and incomplete data. A population pharmacokinetic model that aimed to better characterize maternal and infant exposure to SCIT and its metabolite was developed. METHODS: The study population was composed of women treated by SCIT or racemic citalopram and enrolled in the multicenter prospective cohort study SSRI-Breast Milk study (ClinicalTrial.gov NCT01796132). A joint structural model was first built for SCIT and S-desmethylcitalopram (SDCIT) in plasma using NONMEM and the milk-to-plasma ratio (MPR) was estimated by adding the drug breast milk concentrations. The effect of different influential covariates was tested and the average drug exposure with variability through breastfeeding was predicted under various conditions by simulation. RESULTS: The study enrolled 33 patients treated with SCIT or racemic citalopram who provided 80 blood and 104 milk samples. Mean MPR for both parent drug and metabolite was 1.9. Increased milk fat content was significantly associated with an increased drug transfer into breast milk (+28% for SCIT and +18% for SDCIT when fat amount doubles from 3.1 to 6.2 g/100 mL). Simulations suggested that an exclusively breastfed infant would ingest daily through breast milk 3.3% of the weight-adjusted maternal SCIT dose on average. CONCLUSION: The moderate between-subject variability in milk concentration of SCIT and the limited exposure to escitalopram through breast milk observed provide reassurance for treated mothers of breastfed healthy infants.
Authors: Allen A Mitchell; Suzanne M Gilboa; Martha M Werler; Katherine E Kelley; Carol Louik; Sonia Hernández-Díaz Journal: Am J Obstet Gynecol Date: 2011-04-22 Impact factor: 8.661
Authors: A Panchaud; F Garcia-Bournissen; C Csajka; J H Kristensen; A Taddio; K F Ilett; E J Begg; S Ito Journal: Clin Pharmacol Ther Date: 2011-04-27 Impact factor: 6.875
Authors: Jan Øystein Berle; Vidar M Steen; Trond Oskar Aamo; Harald Breilid; Kolbjørn Zahlsen; Olav Spigset Journal: J Clin Psychiatry Date: 2004-09 Impact factor: 4.384