Group 1: drugs involved in clinical cholestasis | | | | |
BOS | Antihypertensive | Aminotransferase elevation; increase in serum BAs | BSEP inhibitiona; substrate for OATP, NTCP, and MRP2b | Fattinger et al. (2001), Mano et al. (2007), Treiber et al. (2007), LiverTox website (http://livertox.nih.gov/) |
CPZ | Antipsychotic | Intrahepatic cholestasis; hepatocellular necrosis; phospholipidosis | Oxidative stress; mitochondrial membrane potential loss; pericanalicular F-actin disorganization | Velayudham and Farrell (2003), Padda et al. (2011), Anthérieu et al. (2013), LiverTox website (http://livertox.nih.gov/) |
CsA | Immunosuppressant | Cholestasis; hyperbilirubinemia; aminotransferase elevation | Oxidative stress; BSEP, MRP2, and MDR1 inhibitionb; BA transport alteration; pericanalicular F-actin disorganization | Mihatsch et al. (1998), Sharanek et al. (2015) |
NEF | Antidepressant | Cholestasis hepatitis; hepatocellular necrosis | Inhibition of mitochondrial respiration; BSEP inhibitiona | Spigset et al. (2003), Kostrubsky et al. (2006), Dykens et al. (2008), Morgan et al. (2010), LiverTox website (http://livertox.nih.gov/) |
TRO | Antidiabetic | Serious idiosyncratic liver injury; hepatocyte necrosis; cholestatic hepatitis | BA transporter inhibition; mitochondrial dysfunction; BSEP inhibitiona | Watkins and Whitcomb (1998), Morgan et al. (2010), LiverTox website (http://livertox.nih.gov/) |
Group 2: drugs involved in rare cases of clinical cholestasis | | | | |
CIM | Histamine 2-receptor antagonist | Hepatocellular/cholestatic injury | BSEP inhibitiona | Mohi-ud-din and Lewis (2004), Pedersen et al. (2013), LiverTox website (http://livertox.nih.gov/) |
DIC | NSAID | Cholestasis; aminotransferase elevation | BSEP inhibitiona; BSEP and MRP2 inhibitionb | Banks et al. (1995), Pedersen et al. (2013), LiverTox website (http://livertox.nih.gov/), P. Krajcsi (unpublished data) |
ENT | Antiparkinsonian | Mild jaundice and cholestatic pattern; aminotransferase elevation | BSEP and NTCP inhibitiona; mitochondrial dysfunction | Fisher et al. (2002), Longo et al. (2016), LiverTox website (http://livertox.nih.gov/), P. Krajcsi (unpublished data) |
MET | Antidiabetic | Cholestatic hepatitis; mixed hepatocellular and cholestatic injury | BA accumulation; liver mitochondria injury; BSEP inhibitiona | Nammour et al. (2003), Saadi et al. (2013), LiverTox website (http://livertox.nih.gov/), P. Krajcsi (unpublished data) |
PER | Prophylactic antianginal | Steatohepatitis; rare cases of cholestasis | ROS formation; lipid peroxidation; BSEP and NTCP inhibitiona | Feuer and Di Fonzo (1992), P. Krajcsi (unpublished data) |
TAC | Immunosuppressant | Cholestasis after transplantation (Infant); moderate aminotransferase elevation | BSEP inhibitiona; BSEP and NTCP inhibitionb; BSEP internalizationb | Mihatsch et al. (1998), Sharanek et al. (2014), LiverTox website (http://livertox.nih.gov/) |
TOL | Antiparkinsonian | Aminotransferase elevation; intrahepatic cholestasis | ROS formation; mitochondrial toxicity; NTCP, BSEP, MRP2, MRP3, and MRP4 inhibitiona; reactive metabolite | Smith et al. (2003), Morgan et al. (2013), Longo et al. (2016), P. Krajcsi (unpublished data) |
Group 3: drugs not involved in clinical cholestasis | | | | |
AMI | Antiarrhythmic | Steatosis; phospholipidosis; aminotransferase elevation | Phospholipidosis; steatosis | Fromenty and Pessayre (1995), Anthérieu et al. (2011) |
APAP | Analgesic and antipyretic | Acute liver failure; aminotransferase elevation | Lactate dehydrogenase increase; mitochondrial damage | McGill et al. (2012), Toyoda et al. (2012) |
BUS | Hypnotic | Rare aminotransferase elevation with no link to clinically apparent liver injury | No inhibition of mitochondrial respiration | Kostrubsky et al. (2006), Dykens et al. (2008), LiverTox website (http://livertox.nih.gov/) |
FIA | Antiviral | Liver failure associated with lactic acidosis; mitochondrial toxicity | Mitochondrial and cellular toxicity | Tujios and Fontana (2011) |
PIO | Antidiabetic (PPAR-γ agonist) | No aminotransferase elevation | MRP2 stimulation; BSEP and MRP4 inhibitiona | Morgan et al. (2010), LiverTox website (http://livertox.nih.gov/) |
XIM | Anticoagulant | Immune toxicity: aminotransferase elevation | No formation of reactive metabolites | Kenne et al. (2008), Keisu and Andersson (2010) |