IMPACT OF PREGNANCY ON PHARMACOKINETICS OF MEDICATIONS
Main Article Content
Keywords
Pharmacokinetics, pharmacodynamics, drug metabolism, cytochrome P450, drug clearance, drug disposition, physiological changes, pregnancy
Abstract
Pregnancy is associated with significant physiological changes that alter the pharmacokinetics and pharmacodynamics of medications during pregnancy. This overview describes the effects of pregnancy on kidney filtration, drug transport, drug metabolism, protein binding, and their clinical implications for drug therapy.
References
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17. Hebert MF, Ma X, Naraharisetti SB, Krudys KM, Umans JG, Hankins GD, Caritis SN, Miodovnik M, Mattison DR, Unadkat JD, Kelly EJ, Blough D, Cobelli C, Ahmed MS, Snodgrass WR, Carr DB, Easterling TR, Vicini P. Obstetric-Fetal Pharmacology Research Unit Network. Are we optimizing gestational diabetes treatment with glyburide? The pharmacologic basis for better clinical practice. Clin Pharmacol Ther 2009;85(6):607-614.
18. Phelps RL, Metzger BE, Freinkel N. Carbohydrate metabolism in pregnancy. XVII. Diurnal profiles of plasma glucose, insulin, free fatty acids, triglycerides, cholesterol, and individual amino acids in late normal pregnancy. Am J Obstet Gynecol 1981;140(7):730-736.
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21. Hebert MF, Zheng S, Hays K, Shen DD, Davis CL, Umans JG, Miodovnik M, Thummel KE, Easterling TR. Interpreting tacrolimus concentrations during pregnancy and postpartum. Transplantation 2013;95(7):908-915.
2. Hebert MF, Carr DB, Anderson GD, Blough D, Green GE, Brateng DA, Kantor E, Benedetti TJ, Easterling TR. Pharmacokinetics and pharmacodynamics of atenolol during pregnancy and postpartum. J Clin Pharmacol 2005;45(1):25-33.
3. Andrew MA, Easterling TR, Carr DB, Shen D, Buchanan ML, Rutherford T, Bennett R, Vicini P, Hebert MF. Amoxicillin pharmacokinetics in pregnant women: modeling and simulations of dosage strategies. Clin Pharmacol Ther 2007;81(4):547-556.
4. Hebert MF, Easterling TR, Kirby B, Carr DB, Buchanan ML, Rutherford T, Thummel KE, Fishbein DP, Unadkat JD. Effects of pregnancy on CYP3A and P-glycoprotein activities as measured by disposition of midazolam and digoxin: a University of Washington specialized center of research study. Clin Pharmacol Ther 2008;84(2):248-253.
5. Eyal S, Easterling TR, Carr D, Umans JG, Miodovnik M, Hankins GD, Clark SM, Risler L, Wang J, Kelly EJ, Shen DD, Hebert MF. Pharmacokinetics of metformin during pregnancy. Drug Metab Dispos 2010;38(5):833-840.
6. Unadkat JD, Wara DW, Hughes MD, Mathias AA, Holland DT, Paul ME, Connor J, Huang S, Nguyen BY, Watts DH, Mofenson LM, Smith E, Deutsch P, Kaiser KA, Tuomala RE. Pharmacokinetics and safety of indinavir in human immunodeficiency virus-infected pregnant women. Antimicrob Agents Chemother 2007;51(2):783-786.
7. Hebert MF. Impact of Pregnancy on Maternal Pharmacokinetics of Medications, chapter in Clinical Pharmacology During Pregnancy, San Diego: Elsevier; 2013.
8. Davison JM, Dunlop W, Ezimokhai M. 24-hour clearance during the third trimester of normal pregnancy. Br J Obstet Gynaecol1980;87:106-109.
9. Davison JM, Noble MC. Serial changes in 24 hour creatinine clearance during normal menstrual cycles and the first trimester of pregnancy. Br J Obstet Gynaecol 1981;88,10-17.
10. Inglesby TV, O'Toole T, Henderson DA, Bartlett JG, Ascher MS, Eitzen E, Friedlander AM, Gerberding J, Hauer J, Hughes J, McDade J, Osterholm MT, Parker G, Perl TM, Russell PK, Tonat K; Working Group on Civilian Biodefense. Anthrax as a biological weapon, 2002: updated recommendations for management. JAMA 2002;287(17):2236-2252.
11. ACOG Committee on Obstetric Practice. ACOG Committee Opinion number 268, February 2002. Management of asymptomatic pregnant or lactating women exposed to anthrax. American College of Obstetricians and Gynecologists. Obstet Gynecol 2002;99(2):366-368.
12. Pharmaceutical Sales 2010, Drugs.com: Pharmaceutical Sales 2010 [Internet]. Top 200 drugs for 2010 by units sold. http://www.drugs.com/top200_units.html (August 10, 2013)
13. Tracy TS, Venkataramanan R, Glover DD, Caritis SN; National Institute for Child Health and Human Development Network of Maternal-Fetal-Medicine Units. Temporal changes in drug metabolism (CYP1A2, CYP2D6 and CYP3A Activity) during pregnancy. Am J Obstet Gynecol 2005;192(2):633-639.
14. McGready R, Stepniewska K, Seaton E, Cho T, Cho D, Ginsberg A, Edstein MD, Ashley E, Looareesuwan S, White NJ, Nosten F. Pregnancy and use of oral contraceptives reduces the biotransformation of proguanil to cycloguanil. Eur J Clin Pharmacol 2003;59(7):553-537.
15. Högstedt S, Lindberg B, Peng DR, Regårdh CG, Rane A. Pregnancy-induced increase in metoprolol metabolism. Clin Pharmacol Ther 1985;37(6):688-692.
16. Yerby MS, Friel PN, McCormick K, Koerner M, Van Allen M, Leavitt AM, Sells CJ, Yerby JA. Pharmacokinetics of anticonvulsants in pregnancy: alterations in plasma protein binding. Epilepsy Res 1990;5(3):223-8.
17. Hebert MF, Ma X, Naraharisetti SB, Krudys KM, Umans JG, Hankins GD, Caritis SN, Miodovnik M, Mattison DR, Unadkat JD, Kelly EJ, Blough D, Cobelli C, Ahmed MS, Snodgrass WR, Carr DB, Easterling TR, Vicini P. Obstetric-Fetal Pharmacology Research Unit Network. Are we optimizing gestational diabetes treatment with glyburide? The pharmacologic basis for better clinical practice. Clin Pharmacol Ther 2009;85(6):607-614.
18. Phelps RL, Metzger BE, Freinkel N. Carbohydrate metabolism in pregnancy. XVII. Diurnal profiles of plasma glucose, insulin, free fatty acids, triglycerides, cholesterol, and individual amino acids in late normal pregnancy. Am J Obstet Gynecol 1981;140(7):730-736.
19. de Haan GJ, Edelbroek P, Segers J, Engelsman M, Lindhout D, Dévilé-Notschaele M, Augustijn P. Gestation-induced changes in lamotrigine pharmacokinetics: a monotherapy study. Neurology 2004;63(3):571-573.
20. Drugs@FDA: FDA Approved drug products [Internet]. Silver Spring, MD: U.S. Food and Drug Administration, Center for Drug Evaluation and Research. Prograf Label; August 14, 2012. http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/050708s041,050709s034lbl.pdf (June 8, 2013)
21. Hebert MF, Zheng S, Hays K, Shen DD, Davis CL, Umans JG, Miodovnik M, Thummel KE, Easterling TR. Interpreting tacrolimus concentrations during pregnancy and postpartum. Transplantation 2013;95(7):908-915.