Table 2.
Altered Transporter-Mediated Drug Disposition in Liver Disease Resulting in Changes in Pharmacokinetics and/or Efficacy
| Liver Disease | Drug | Drug Class | Altered Drug Disposition | Implicated Transport Protein | References |
|---|---|---|---|---|---|
|
|
|
|
|
|
|
| Cholestasis | Doxorubicin | Chemotherapeutic | ↑ systemic concentrations | Mrp2 (rodent) | 100 |
| Metformin | Antidiabetic | ↓ systemic clearance and hepatic uptake; ↓ suppression of glucose production | Oct1 (rodent) | 99 | |
|
|
|
|
|
|
|
| HCV | Nelfinavir | Antiretroviral | ↑ systemic concentrations | P-gp (human) | 115 |
| 99mTc-mebrofenin | Hepatobiliary imaging agent | ↓ hepatic uptake, ↑ Tmax, ↓ hepatic excretion | OATP, MRP2(human) | 116 | |
|
|
|
|
|
|
|
| HCC | Gd-EOB-DTPA | Hepatobiliary contrast agent | ↑ or ↓ signal intensity | OATP1B1 (human) OATP1B3(human) MRP2 (human) |
19,20 |
| Methotrexate | Antimetabolite | ↑ or ↓ systemic concentrations | OATP1B1 (transgenic mice) | 208 | |
|
|
|
|
|
|
|
| HIV | Indinavir, Nelfinavir, Saquinavir | Protease inhibitors | ↑ or ↓ systemic concentrations | Mdr1a (rodent) | 209 |
|
|
|
|
|
|
|
| NASH | APAP/APAP-glucuronide | Analgesic | ↑ systemic concentrations; ↓ biliary excretion | MRP3 (human); Mrp2/Mrp3 (rodent) | 74 |
| Morphine/morphine-glucuronide | Analgesic | ↑ systemic concentrations | MRP3 (human) | 183 | |
| 99mTc-mebrofenin | Hepatobiliary imaging agent | ↑ systemic concentrations; ↑ hepatic exposure | OATP, MRP2, MRP3 (human) | 2 | |
| Gd-EOB-DTPA | Hepatobiliary contrast agent | ↑ hepatic exposure | Mrp2 (rodent) | 184 | |
| Methotrexate | Chemotherapeutic | ↑ liver and ↑ GI toxicity | Mrp1–4, Mdr1 P-gp, Bcrp (rodent) | 207 | |
| Pemetrexed | Chemotherapeutic | ↑ systemic concentrations; ↓ biliary excretion | Mrp2 (rodent) | 210 | |
| Simvastatin | Cholesterol-lowering | ↑ systemic concentrations | Oatp (rodent) | 175 | |
|
|
|
|
|
|
|
| PBC/cirrhosis | Gd-EOB-DTPA | Hepatobiliary contrast agent | ↓ hepatic signal intensity | OATP (human) | 192 |
Abbreviations: data not available (-); hepatocellular carcinoma (HCC); hepatitis C virus (HCV); human immunodeficiency virus (HIV); nonalcoholic steatohepatitis (NASH); primary biliary cholangitis (PBC), ↑ increased, ↓ decrease