Table 4:
Gastrointestinal system, hepatic enzymes and transporter changes during normal pregnancy.
| Gastrointestinal changes | Direction and magnitude of change in pregnancy |
|---|---|
|
| |
| Transporter changes in the gut | Decreased [122] |
| ABC | Increased BRCP expression in pregnant mice (30–55%) [123] |
| BCRP | GLUT2 is increased during pregnancy |
| GLUT2 | Increased expression of P-gp in pregnant mice [120] |
| MDR1 (P-gp) | Decreased MRP1 expression in pregnant mice (30–40%) [123] |
| MRP1 | Decreased MRP2 expression in pregnant mice (30–40%) [123] |
| MRP2 | Decreased expression of MRP3 in pregnant mice |
| MRP3 | No change in OSTα expression [123] |
| OST alpha | No change/minimal increase in OSTβ expression [123] |
| OST beta | No change in expression of intestinal CYP3A4 [120, 124] |
| CYP3A4 | No change in expression of intestinal CYP3A5 [120, 124] |
| CYP3A5 | |
|
| |
| Hepatic changes | Direction and magnitude of change in pregnancy |
|
| |
| CYP expression in the liver | Decrease in CYP1A2 during pregnancy [94] |
| CYP1A2 | Increases |
| CYP2B6 | Increases |
| CYP2C9 | Decrease in CYP2C19 during pregnancy |
| CYP2C19 | Increases in CYP2D6 during pregnancy [94] |
| CYP2D6 | Increases |
| CYP2E16 | Increases [94] |
| CYP3A3 | Increases [94] |
| CYP3A4 | Increases [94] |
| CYP3A5 | Increases [94] |
| CYP3A7 | Increases [125] |
| UGT activity | Expression of cathepsin A increase during pregnancy [17] |
| Cathepsin A | Expression of CES1 is unchanged during pregnancy [18] |
| Carboxyesterase type 1 (CES1) | >50% decrease in expression of ABCG5 in hepatocytes of pregnant mice [88] |
| Hepato-biliary transporter changes | |
| ABCG5 | >50% decrease in expression of ABCG8 in hepatocytes of pregnant mice [88] |
| ABCG8 | ATP8B1 decrease in pregnant mice [88] and women with cholestasis [126] |
| ATP8B1 | Decreased expression in hepatocytes of pregnant mice [88] |
| BRCP (ABCG2) | Decreases expression of BSEP in hepatocytes of pregnant mice [88] |
| BSEP – Bile salt export pump | >50% decreased expression of ENT1 in pregnant mice [88] |
| ENT1 | Decreased expression of ENT2 in pregnancy |
| ENT2 | Decreased expression in pregnant mice [88] |
| MATE1 | Bile acid transporter (MDR3) |
| MDR3 | Unchanged in hepatocytes of pregnant rats [127] |
| MRP1 | Decreased expression of MRP2 in biliary system of pregnant rats [119]. |
| MRP2 (ABCC2) – Bile acid transporter | 50% decreased expression of MRP3 in hepatocytes of pregnant rats [127] |
| MRP3 (ABCB4) – Bile acid transporter | 63% increased expression of MRP4 in hepatocytes of pregnant rats [88] |
| MRP4 – Bile acid transporter | 60% decreased expression of MRP6 in hepatocytes of pregnant rats [127] |
| MRP6 | 70% increased expression of OAT2 in hepatocytes of pregnant mice [88] |
| OAT2 | OAT7 is only found in the liver (hepatic specific). |
| OAT7 | Relatively unchanged of OATP1B1 in hepatocytes of pregnant rats and humans [19, 127] |
| OATP1B1 | 50% decreased expression of OATP1B2 in hepatocytes of pregnant rats [127] |
| OATP1B2 | Decreased expression of OAT1B3 in pregnant women with cholestasis [19] |
| OATP1B3 | Decreased expression of OATP2B1 in hepatocytes of pregnant mice [88] |
| OATP2B1 | >50% decreased expression of OCT1 in hepatocytes of mice [88] |
| OCT1 | Decreased expression of OST (alpha and beta) during pregnancy |
| OST – Bile acid transporter | Unchanged MRD1 expression in the liver [120] |
| P-gp (MRD1) | |
ABC, ATP binding cassette; ABCG, ATP-binding cassette super-family G; BCRP, Breast cancer receptor protein; CYP, cytochrome P450; ENT, equilibrative nucleoside transporters; GLUT, glucose transporter; MATE, Multiantimicrobial extrusion protein; MDR, multi-drug resistance mutation, MRP, multidrug resistance protein; OAT, organic anionic transporter; OCT, organic cationic transporter; OST, Organic solute and steroid transporter; UGT, uridine 5′-diphospho-glucuronosyltransferase.