Drug metabolism and transport during pregnancy: How does drug disposition change during pregnancy and what are the mechanisms that cause such changes?

Drug Metabolism and Disposition

Volumn 41, Issue 2, 2013, Pages 256-262

  Isoherranen, Nina ^a   Thummel, Kenneth E ^a  

^a UNIVERSITY OF WASHINGTON   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACICLOVIR; CYTOCHROME P450 1A2; CYTOCHROME P450 2B6; CYTOCHROME P450 2C9; CYTOCHROME P450 2D6; CYTOCHROME P450 3A4; DIGOXIN; EFAVIRENZ; ESTROGEN; GLIBENCLAMIDE; GLUCURONOSYLTRANSFERASE 1A4; GLUCURONOSYLTRANSFERASE 2B7; GROWTH HORMONE; LAMIVUDINE; LAMOTRIGINE; METFORMIN; METOPROLOL; MIDAZOLAM; MULTIDRUG RESISTANCE PROTEIN; ORGANIC ANION TRANSPORTER; ORGANIC ANION TRANSPORTER 1; ORGANIC ANION TRANSPORTER 3; ORGANIC CATION TRANSPORTER; ORGANIC CATION TRANSPORTER 2; OSELTAMIVIR; PHENYTOIN; PROGESTERONE; THEOPHYLLINE; UNINDEXED DRUG; ZIDOVUDINE;

DRUG CLEARANCE; DRUG DISPOSITION; DRUG METABOLISM; DRUG SAFETY; DRUG TRANSPORT; ENZYME ACTIVITY; EVIDENCE BASED MEDICINE; FIRST TRIMESTER PREGNANCY; HUMAN; IN VITRO STUDY; MEDICAL RESEARCH; NONHUMAN; PREDICTION; PREGNANCY; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; SECOND TRIMESTER PREGNANCY; THIRD TRIMESTER PREGNANCY; TREATMENT OUTCOME;

ADRENAL GLANDS; ANIMALS; ARYLDIALKYLPHOSPHATASE; ATP-BINDING CASSETTE TRANSPORTERS; CARBOXYLESTERASE; CHOLESTASIS; COTININE; CYTOCHROME P-450 ENZYME SYSTEM; ESTRADIOL; ESTROGEN RECEPTOR ALPHA; ESTROGENS; ETHINYL ESTRADIOL; FEMALE; FETUS; GENE EXPRESSION REGULATION, DEVELOPMENTAL; GLUCURONOSYLTRANSFERASE; HEPATOCYTES; HUMANS; HYDROXYPROGESTERONES; INTESTINE, SMALL; KIDNEY; LIVER; LUNG; MALE; MATERNAL BEHAVIOR; MEMBRANE TRANSPORT PROTEINS; MULTIDRUG RESISTANCE-ASSOCIATED PROTEINS; ORGANIC ANION TRANSPORTERS; PESTICIDES; PLACENTA; PREGNANCY; PROGESTERONE; RNA, MESSENGER; SMOKING; TAUROCHOLIC ACID;

ANIMALIA;

EID: 84872714794     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.112.050245     Document Type: Review

References (62)

1. Abduljalil K, Furness P, Johnson TN, Rostami-Hodjegan A, and Soltani H (2012) Anatomical, physiological and metabolic changes with gestational age during normal pregnancy: a database for parameters required in physiologically based pharmacokinetic modelling. Clin Pharmacokinet 51:365-396.
2. Anderson GD (2005) Pregnancy-induced changes in pharmacokinetics: a mechanistic-based approach. Clin Pharmacokinet 44:989-1008. (Pubitemid 41356388)
3. Andrade SE, Gurwitz JH, Davis RL, Chan KA, Finkelstein JA, Fortman K, McPhillips H, Raebel MA, Roblin D, and Smith DH, et al. (2004) Prescription drug use in pregnancy. Am J Obstet Gynecol 191:398-407. (Pubitemid 39178690)
4. Beigi RH, Han K, Venkataramanan R, Hankins GD, Clark S, Hebert MF, Easterling T, Zajicek A, Ren Z, and Mattison DR, et al.; Obstetric-Fetal Pharmacology Research Units Network (2011) Pharmacokinetics of oseltamivir among pregnant and nonpregnant women. Am J Obstet Gynecol 204(6, Suppl 1)S84-S88.
5. Buchanan ML, Easterling TR, Carr DB, Shen DD, Risler LJ, Nelson WL, Mattison DR, and Hebert MF (2009) Clonidine pharmacokinetics in pregnancy. Drug Metab Dispos 37: 702-705.
6. Carter BL, Driscoll CE, and Smith GD (1986) Theophylline clearance during pregnancy. Obstet Gynecol 68:555-559. (Pubitemid 16014512)
7. Chamberlain A, White S, Bawdon R, Thomas S, and Larsen B (1993) Pharmacokinetics of ampicillin and sulbactam in pregnancy. Am J Obstet Gynecol 168:667-673. (Pubitemid 23069134)
8. Cheng C, Alexander R, Min R, Leng J, Yip KY, Rozowsky J, Yan KK, Dong X, Djebali S, and Ruan Y, et al. (2012) Understanding transcriptional regulation by integrative analysis of transcription factor binding data. Genome Res 22:1658-1667.
9. Choi SY, Fischer L, Yang K, Chung H, and Jeong H (2011) Isoform-specific regulation of cytochrome P450 expression and activity by estradiol in female rats. Biochem Pharmacol 81: 777-782.
10. Choi SY, Koh KH, and Jeong H (2013) Isoform-specific regulation of cytochromes p450 expression by estradiol and progesterone. Drug Metab Dispos 41:263-269.
11. Claessens AJ, Risler LJ, Eyal S, Shen DD, Easterling TR, and Hebert MF (2010) CYP2D6 mediates 4-hydroxylation of clonidine in vitro: implication for pregnancy-induced changes in clonidine clearance. Drug Metab Dispos 38:1393-1396.
12. Coller JK, Somogyi AA, and Bochner F (1999) Comparison of (S)-mephenytoin and proguanil oxidation in vitro: contribution of several CYP isoforms. Br J Clin Pharmacol 48:158-167. (Pubitemid 29349451)
13. Cressey TR, Stek A, Capparelli E, Bowonwatanuwong C, Prommas S, Sirivatanapa P, Yuthavisuthi P, Neungton C, Huo Y, and Smith E, et al.; IMPAACT P1026s Team (2012) Efavirenz pharmacokinetics during the third trimester of pregnancy and postpartum. J Acquir Immune Defic Syndr 59:245-252.
14. de Oliveira Baraldi C, Lanchote VL, de Jesus Antunes N, de Jesus Ponte Carvalho TM, Dantas Moisés EC, Duarte G, and Cavalli RC (2011) Metformin pharmacokinetics in nondiabetic pregnant women with polycystic ovary syndrome. Eur J Clin Pharmacol 67:1027-1033.
15. Dickinson RG, Hooper WD, Wood B, Lander CM, and Eadie MJ (1989) The effect of pregnancy in humans on the pharmacokinetics of stable isotope labelled phenytoin. Br J Clin Pharmacol 28:17-27. (Pubitemid 19195661)
16. Dickmann LJ and Isoherranen N (2013) Quantitative Prediction of CYP2B6 Induction by Estradiol During Pregnancy, Potential Explanation for Increased Methadone Clearance during Pregnancy. Drug Metab Dispos 41:270-274.
17. Ekstrom L, Johansson M, and Rane A (2013) Tissue distribution and relative gene expression of udp-glucuronosyltransferases (2B7, 2B15, 2B17) in the human fetus. Drug Metab Dispos 41: 291-295.
18. Eyal S, Easterling TR, Carr D, Umans JG, Miodovnik M, Hankins GD, Clark SM, Risler L, Wang J, and Kelly EJ, et al. (2010) Pharmacokinetics of metformin during pregnancy. Drug Metab Dispos 38:833-840.
19. Feghali MN and Mattison DR (2011) Clinical therapeutics in pregnancy. J Biomed Biotechnol 2011:783528.
20. Fortin MC, Aleksunes LM, and Richardson JR (2013) Alteration of the expression of pesticidemetabolizing enzymes in pregnant mice: potential role in the increased vulnerability of the developing brain. Drug Metab Dispos 41:326-331.
21. Franco V, Mazzucchelli I, Gatti G, Specchio LM, La Neve A, Papantonio A, Ozkaynakçi AE, and Perucca E (2008) Changes in lamotrigine pharmacokinetics during pregnancy and the puerperium. Ther Drug Monit 30:544-547.
22. Frenkel LM, Brown ZA, Bryson YJ, Corey L, Unadkat JD, Hensleigh PA, Arvin AM, Prober CG, and Connor JD (1991) Pharmacokinetics of acyclovir in the term human pregnancy and neonate. Am J Obstet Gynecol 164:569-576.
23. Gaohua L, Abduljalil K, Jamei M, Johnson TN, and Rostami-Hodjegan A (2012) A pregnancy physiologically based pharmacokinetic (p-PBPK) model for disposition of drugs metabolized by CYP1A2, CYP2D6 and CYP3A4. Br J Clin Pharmacol 74:873-885.
24. Glover DD, Amonkar M, Rybeck BF, and Tracy TS (2003) Prescription, over-the-counter, and herbal medicine use in a rural, obstetric population. Am J Obstet Gynecol 188: 1039-1045. (Pubitemid 36530060)
25. Green MD, Bishop WP, and Tephly TR (1995) Expressed human UGT1.4 protein catalyzes the formation of quaternary ammonium-linked glucuronides. Drug Metab Dispos 23:299-302.
26. Haddad J, Langer B, Astruc D, Messer J, and Lokiec F (1993) Oral acyclovir and recurrent genital herpes during late pregnancy. Obstet Gynecol 82:102-104. (Pubitemid 23200551)
27. Hebert MF, Easterling TR, Kirby B, Carr DB, Buchanan ML, Rutherford T, Thummel KE, Fishbein DP, and Unadkat JD (2008) 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 84:248-253.
28. Hebert MF, Ma X, Naraharisetti SB, Krudys KM, Umans JG, Hankins GD, Caritis SN, Miodovnik M, Mattison DR, and Unadkat JD, et al.; Obstetric-Fetal Pharmacology Research Unit Network (2009) Are we optimizing gestational diabetes treatment with glyburide? The pharmacologic basis for better clinical practice. Clin Pharmacol Ther 85:607-614.
29. Högstedt S, Lindberg B, Peng DR, Regårdh CG, and Rane A (1985) Pregnancy-induced increase in metoprolol metabolism. Clin Pharmacol Ther 37:688-692.
30. Hughes RC, Gardiner SJ, Begg EJ, and Zhang M (2006) Effect of pregnancy on the pharmacokinetics of metformin. Diabet Med 23:323-326.
31. Ke B, Nallani S, Zhao P, Rostami-Hodjegan A, and Unadkat J (2012) A PBPK model to predict disposition of cyp3a-metabolized drugs in pregnant women: verification and discerning the site of cyp3a induction. CPT: Pharmacomet Syst Pharmacol 1 DOI: 10.1038/psp.2012.2.
32. Koh KH, Jurkovic S, Yang K, Choi SY, Jung JW, Kim KP, Zhang W, and Jeong H (2012) Estradiol induces cytochrome P450 2B6 expression at high concentrations: implication in estrogen-mediated gene regulation in pregnancy. Biochem Pharmacol 84:93-103.
33. Kusuhara H, Ito S, Kumagai Y, Jiang M, Shiroshita T, Moriyama Y, Inoue K, Yuasa H, and Sugiyama Y (2011) Effects of a MATE protein inhibitor, pyrimethamine, on the renal elimination of metformin at oral microdose and at therapeutic dose in healthy subjects. Clin Pharmacol Ther 89:837-844.
34. Landon MB and Gabbe SG (2011) Gestational diabetes mellitus. Obstet Gynecol 118:1379-1393.
35. Little M, Lyerly A, and Faden R (2009) Pregnant women & medical research: a moral imperative. Bioeth Forum 2:60-64.
36. McGready R, Stepniewska K, Seaton E, Cho T, Cho D, Ginsberg A, Edstein MD, Ashley E, Looareesuwan S, and White NJ, et al. (2003) Pregnancy and use of oral contraceptives reduces the biotransformation of proguanil to cycloguanil. Eur J Clin Pharmacol 59:553-557. (Pubitemid 37363567)
37. Moodley J, Moodley D, Pillay K, Coovadia H, Saba J, van Leeuwen R, Goodwin C, Harrigan PR, Moore KH, and Stone C, et al. (1998) Pharmacokinetics and antiretroviral activity of lamivudine alone or when coadministered with zidovudine in human immunodeficiency virus type 1-infected pregnant women and their offspring. J Infect Dis 178:1327-1333.
38. Muller AE, DeJongh J, Oostvogel PM, Voskuyl RA, Dorr PJ, Danhof M, and Mouton JW (2008a) Amoxicillin pharmacokinetics in pregnant women with preterm premature rupture of the membranes. Am J Obstet Gynecol 198:108 e1-6.
39. Muller AE, Dörr PJ, Mouton JW, De Jongh J, Oostvogel PM, Steegers EA, Voskuyl RA, and Danhof M (2008b) The influence of labour on the pharmacokinetics of intravenously administered amoxicillin in pregnant women. Br J Clin Pharmacol 66:866-874.
40. Mwinyi J, Cavaco I, Pedersen RS, Persson A, Burkhardt S, Mkrtchian S, and Ingelman-Sundberg M (2010) Regulation of CYP2C19 expression by estrogen receptor a: implications for estrogen-dependent inhibition of drug metabolism. Mol Pharmacol 78:886-894.
41. Ohman I, Luef G, and Tomson T (2008) Effects of pregnancy and contraception on lamotrigine disposition: new insights through analysis of lamotrigine metabolites. Seizure 17: 199-202.
42. O'Sullivan MJ, Boyer PJ, Scott GB, Parks WP, Weller S, Blum MR, Balsley J, and Bryson YJ; Zidovudine Collaborative Working Group (1993) The pharmacokinetics and safety of zidovudine in the third trimester of pregnancy for women infected with human immunodeficiency virus and their infants: phase I acquired immunodeficiency syndrome clinical trials group study (protocol 082). Am J Obstet Gynecol 168:1510-1516. (Pubitemid 23153298)
43. Papageorgiou I, Grepper S, and Unadkat JD (2013) Induction of hepatic CYP3A enzymes by pregnancy-related Hormones: studies in human hepatocytes and hepatic cell lines. Drug Metab Dispos 41:281-290.
44. Philipson A (1977) Pharmacokinetics of ampicillin during pregnancy. J Infect Dis 136:370-376. (Pubitemid 8193979)
45. Pond SM, Kreek MJ, Tong TG, Raghunath J, and Benowitz NL (1985) Altered methadone pharmacokinetics in methadone-maintained pregnant women. J Pharmacol Exp Ther 233: 1-6. (Pubitemid 15083518)
46. Reece EA and Moore T (2012) The diagnostic criteria for gestational diabetes: to change or not to change? Am J Obstet Gynecol DOI: 10.1016/j.ajog.2012.10.887 [published ahead of print].
47. Roustit M, Jlaiel M, Leclercq P, and Stanke-Labesque F (2008) Pharmacokinetics and therapeutic drug monitoring of antiretrovirals in pregnant women. Br J Clin Pharmacol 66:179-195.
48. Ruiz ML, Rigalli JP, Arias A, Villanueva S, Banchio C, Vore M, Mottino AD, and Catania VA (2013) Induction of Hepatic Multidrug Resistance Associated Protein 3 by Ethynylestradiol is Independent of Cholestasis and Mediated by Estrogen Receptor. Drug Metab Dispos 41: 275-280.
49. Sharma S, Ellis EC, Gramignoli R, Dorko K, Tahan V, Hansel M, Mattison DR, Caritis SN, Hines RN, and Venkataramanan R, et al. (2013) Hepatobiliary disposition of 17-ohpc and taurocholate in fetal human hepatocytes: a comparison with adult human hepatocytes. Drug Metab Dispos 41:296-304.
50. Shuster DL, Bammler TK, Beyer RP, Macdonald JW, Tsai JM, Farin FM, Hebert MF, Thummel KE, and Mao Q (2013) Gestational age-dependent changes in gene expression of metabolic enzymes and transporters in pregnant mice. Drug Metab Dispos 41:332-342.
51. Tanihara Y, Masuda S, Sato T, Katsura T, Ogawa O, and Inui K (2007) Substrate specificity of MATE1 and MATE2-K, human multidrug and toxin extrusions/H(+)-organic cation antiporters. Biochem Pharmacol 74:359-371. (Pubitemid 46890818)
52. Tomson T, Lindbom U, Ekqvist B, and Sundqvist A (1994) Epilepsy and pregnancy: a prospective study of seizure control in relation to free and total plasma concentrations of carbamazepine and phenytoin. Epilepsia 35:122-130. (Pubitemid 24074475)
53. Topletz A, Le HN, Lee N, Chapman JD, Kelly EJ, Wang J, and Isoherranen N (2013) Hepatic Cyp2d and Cyp26a1 mRNAs and activities are increased during mouse pregnancy. Drug Metab Dispos 41:312-319.
54. Tracy TS, Venkataramanan R, Glover DD, and Caritis SN; National Institute for Child Health and Human Development Network of Maternal-Fetal-Medicine Units (2005) Temporal changes in drug metabolism (CYP1A2, CYP2D6 and CYP3A Activity) during pregnancy. Am J Obstet Gynecol 192:633-639. (Pubitemid 40215007)
55. Ververs FF, Voorbij HA, Zwarts P, Belitser SV, Egberts TC, Visser GH, and Schobben AF (2009) Effect of cytochrome P450 2D6 genotype on maternal paroxetine plasma concentrations during pregnancy. Clin Pharmacokinet 48:677-683.
56. Vyhlidal CA, Riffel AK, Haley KJ, Sharma S, Dai H, Tantisira KG, Weiss ST, and Leeder JS (2013) Cotinine in human placenta predicts induction of gene expression in fetal tissues. Drug Metab Dispos 41:305-311.
57. Watts DH, Brown ZA, Tartaglione T, Burchett SK, Opheim K, Coombs R, and Corey L (1991) Pharmacokinetic disposition of zidovudine during pregnancy. J Infect Dis 163:226-232.
58. Wendland EM, Torloni MR, Falavigna M, Trujillo J, Dode MA, Campos MA, Duncan BB, and Schmidt MI (2012) Gestational diabetes and pregnancy outcomes - a systematic review of the World Health Organization (WHO) and the International Association of Diabetes in Pregnancy Study Groups (IADPSG) diagnostic criteria. BMC Pregnancy Childbirth 12:23.
59. Wolff K, Boys A, Rostami-Hodjegan A, Hay A, and Raistrick D (2005) Changes to methadone clearance during pregnancy. Eur J Clin Pharmacol 61:763-768. (Pubitemid 41674263)
60. Yacovino LL, Gibson CJ, and Aleksunes LM (2013) Down-regulation of brush border efflux transporter expression in the kidneys of pregnant mice. Drug Metab Dispos 41:320-325.
61. Zhang H, Wu X, Wang H, Mikheev AM, Mao Q, and Unadkat JD (2008) Effect of pregnancy on cytochrome P450 3a and P-glycoprotein expression and activity in the mouse: mechanisms, tissue specificity, and time course. Mol Pharmacol 74:714-723.
62. Zheng S, Easterling TR, Umans JG, Miodovnik M, Calamia JC, Thummel KE, Shen DD, Davis CL, and Hebert MF (2012) Pharmacokinetics of tacrolimus during pregnancy. Ther Drug Monit 34:660-670.