Eab Pregnancy Between 50 and 70% of O&: women use at least one medication during pregnancy Adherence may be a o000oc0= problem Women concerned about effect of medicine on fetus Risk usually ①○×① overestimated Mitchell AA, et al. Am J Obstet Gynecol 2011, 205: 51 e1-e8 o' Neilsen MJ, et al. Aliment Pharmcol Ther 2010: 32: 49-58 KENTUCKY Nordeng H, et al. Eur J Clin Pharmacol 2010: 66: 207-14 College of Pharmacy
Pregnancy • Between 50 and 70% of women use at least one medication during pregnancy • Adherence may be a problem – Women concerned about effect of medicine on fetus – Risk usually overestimated Mitchell AA, et al. Am J Obstet Gynecol 2011;205:51 e1-e8. Neilsen MJ, et al. Aliment Pharmcol Ther 2010;32:49-58. Nordeng H, et al. Eur J Clin Pharmacol 2010;66:207-14
a Maternal Pharmacokinetic Changes Absorption o4. Gastric emptying and o&: small intestinal motility 00 decreased Particularly in 3 rd trimester o000oc0= ∴· Nausea and vomiting KENTUCKY College of Pharmacy
Maternal Pharmacokinetic Changes - Absorption • Gastric emptying and small intestinal motility decreased – Particularly in 3rd trimester • Nausea and vomiting
a Maternal Pharmacokinetic Changes Distribution of. Plasma volume expansion of50% 00 Vd increase, particularly with smally, medicines decreases serum concentration most o000oc0= important for loading doses Hypoalbuminemia due to dilution, decreased plasma rotein binding increased Cfi also increased availability for metabolism KENTUCKY Loebstein R, Koren G. Ther Drug Monit 2002: 24: 15-22 College of Pharmacy
Maternal Pharmacokinetic Changes - Distribution • Plasma volume expansion of 50% – Vd increase, particularly with small Vd medicines, decreases serum concentration; most important for loading doses – Hypoalbuminemia due to dilution, decreased plasma protein binding, increased Cf ; also increased availability for metabolism Loebstein R, Koren G. Ther Drug Monit 2002;24:15-22
a Maternal Pharmacokinetic Changes Metabolism o. Increased hepatic blood flow o.:,- Increased metabolism of some 00 medicines; particularly in 3rd trimester CYP3A4. CYP2D6, CYP2A6 o000oc0= CYP2C9, and ugt activity increased CYP1A2, CYP2C19 activity decreased Hodge LS, Tracy TS. Expert Opin Drug Metab Toxicol 2007, 3: 557-71 Pavek P, et al. Curr Drug Metab 2009; 10: 520-9 KENTUCKY O).. Dawes M, Chowienczyk PK Best Pract Res Clin Obstet Gynaecol 2001: 15: 819-26. College of Pharmacy
Maternal Pharmacokinetic Changes - Metabolism • Increased hepatic blood flow – Increased metabolism of some medicines; particularly in 3rd trimester • CYP3A4, CYP2D6, CYP2A6, CYP2C9, and UGT activity increased • CYP1A2, CYP2C19 activity decreased Hodge LS, Tracy TS. Expert Opin Drug Metab Toxicol 2007;3:557-71. Pavek P, et al. Curr Drug Metab 2009;10:520-9. Dawes M, Chowienczyk PK. Best Pract Res Clin Obstet Gynaecol 2001;15:819-26
a Maternal Pharmacokinetic Changes Elimination oi. Renal blood flow ad, increases by 25-50% =·G| omerular filtration rate increases by 50% KENTUCKY Loebstein R, Koren G. Ther Drug Monit 2002: 24: 15-22 College of Pharmacy
Maternal Pharmacokinetic Changes - Elimination • Renal blood flow increases by 25-50% • Glomerular filtration rate increases by 50% Loebstein R, Koren G. Ther Drug Monit 2002;24:15-22