Investigating Sources of Variability in Pharmacological Response to Nausea and Vomiting of Pregnancy

• Main Author: Gill, Simerpal
• Other Authors: Koren, Gideon
• Language: en_ca
• Published: 2010
• Subjects: nausea and vomiting of pregnancy; pregnancy; 0419; 0383
• Online Access: http://hdl.handle.net/1807/24348

Nausea and vomiting of pregnancy (NVP) is the most common medical condition in pregnancy, and, unfortunately, variability exists among pregnant women in the therapeutic effect of anti-emetics as well as in factors that can exacerbate NVP. Identifying and managing these sources of variability will result in significant improvements in the quality of life of pregnant woman. This dissertation addressed clinical pharmacology strategies in managing NVP by focusing on three predominant areas of variability. The first challenge addressed in this dissertation was women with pre-existing gastrointestinal (GI) conditions and adherence and tolerability to prenatal multivitamin supplementation. To identify the role of iron in reducing adherence and increasing NVP and GI symptoms, two separate studies were conducted. In the first study, women randomized to a prenatal multivitamin supplementation with higher iron content experienced more adverse GI effects and increased severity of NVP symptoms. In the second study, after discontinuing iron-containing prenatal multivitamins, two-thirds of women in a prospective cohort reported improvement in their NVP symptoms which was corroborated with validated scales to quantify NVP severity. The second challenge addressed in this dissertation was the effect of heartburn and acid reflux on the severity of NVP. In a controlled, prospective study, women experiencing heartburn and acid reflux experienced greater severity of NVP compared to women with no GI symptoms. Furthermore, treatment of heartburn and acid reflux with acid-reducing pharmacotherapy with associated with a reduction in GI symptoms and NVP severity. Therefore, histamine 2 blockers or proton pump inhibitors, which do not appear to be associated with increased fetal risks, should be administered when required. The third clinical pharmacology challenge addressed in this dissertation was to determine the pharmacokinetic variability of the active ingredients of Diclectin®, first-line pharmacotherapy for the treatment of NVP. Large variability was observed in the area under the curve for both active metabolites: a 6.5-fold difference for pyridoxal-5’-phosphate and a 2.1-fold difference for doxylamine. Whether these pharmacokinetic differences contribute to suboptimal efficacy remains to be determined. In conclusion, based on the results presented in this dissertation, several improvements in clinical pharmacology strategies can be made to enhance management of NVP.