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. 2020 Jul 27;72(5):1173–1194. doi: 10.1007/s43440-020-00139-6

Table 2.

Summary of drug transporter studies in pathological states

Transporter Model/patients mRNA Protein Function References
Kidney failure
 ABCB1/P-gp Caco2, IS, CMPF – – ↓ Cyclosporine transport [18]
 ABCB1/P-gp Caco2, plasma from CRF rats – – ↓ 1.5-fold Rho123 transport [15]
 Mdr1/P-gp Enterocytes, rat – ↓ Twofold – [17]
 ABCB1/P-gp Caco2, plasma from CRF rats – – ↓ 1.4-fold Rho123 transport [16]
 Mdr1/P-gp Enterocytes, rat, plasma from CRF rats – ↓ 1.3-fold, WB – [16]
 Mdr1/P-gp Rat, gentamycin induced ARF – –

↓ 1.4-fold Rho123 exsorption clearance

↓ 1.1-fold cyclosporine A exsorption clearance, duodenal loop

 [18]
 Mdr1a/P-gp Rat, 7/8 nephrectomy  ↔ Jejunum, cPCR  ↔ Intestine, ELISA ↓ Rho123 transport, everted gut sac [20]
 Mdr1a/P-gp Rat, 5/6 nephrectomy  ↔ Intestine, qRT-PCR ↓ 2.8-fold, intestine, WB ↓ 1.4-fold, Rho123 transport, everted gut [16]
 Mdr1a/P-gp Rat, cisplatin induced ARF – –

↑ 1.3-fold tacrolimus bioavailability,

↑ 1.8-fold tacrolimus AUC0–30 in situ loop method—upper intestine

 [21]
 ABCC2/MRP2 Caco2, plasma from CRF rats – – ↓ 1.3-fold, CDF transport [16]
 ABCC2/MRP2 Enterocytes, rat, plasma from CRF rats – ↓ 1.3-fold, WB – [16]
 Abcc2/Mrp2 Rat, 5/6 nephrectomy  ↔ Intestine, qRT-PCR ↓ 2.5 fold, intestine, WB ↓ 1.3-fold, CDF transport, everted gut [16]
 Abcc3/Mrp3 Rat, 5/6 nephrectomy  ↔ Ileum, qRT-PCR  ↔ Ileum, WB – [26]
 Abcg2/Bcrp Rat, 5/6 nephrectomy

 ↔ Duodenum,

 ↔ Jejunum,

↑ 1.5-fold, ileum,

 ↔ Colon, qRT-PCR

 – – [22]
 Slco1a5/Oatp1a5 Enterocytes, rat –  ↔  – [17]
 Slco2/Oatp2 Rat, 5/6 nephrectomy –  ↔ Intestine, WB – [16]
 Slco3/Oatp3 Rat, 5/6 nephrectomy  ↔ Intestine, qRT-PCR  ↔ Intestine, WB – [16]
 Slc10a2/Asbt Rat, 5/6 nephrectomy  ↔ Ileum, qRT-PCR  ↔ Ileum, WB [26]
 Slc15a1/Pept1 Rat, 5/6 nephrectomy

 ↔ Duodenum

 ↔ Jejunum

 ↔ Ileum, cPCR

↑ Duodenum

 ↔ Jejunum

 ↔ Ileum, WB

↑ 2.3-fold AUC glycylsarcosine

↑ 1.8-fold AUC ceftibuten

 [27]
 Slc51a/OSTα Rat, 5/6 nephrectomy  ↔ Ileum, qRT-PCR  ↔ Ileum, WB – [26]
 Slc51b/Ostβ Rat, 5/6 nephrectomy  ↔ Ileum, qRT-PCR  ↔ Ileum, WB – [26]
Liver failure
 Abcb1/Mdr1 Caco2, plasma from ALF rats – – ↓ 1.4-fold rhodamine transport [32]
 Abcb1/Mdr1 Caco2, plasma from ALF rats – – ↓ 1.3-fold rhodamine transport [28]
 Abcb1/Mdr1 Rat, ALF, thioacetamide – ↑ 2.9-fold, intestine, WB

↑ 1.6-fold AUC, zidovudine,

↑ 1.7-fold, accumulative absorption, rhodamine 123

 [30]
 Abcb1/Mdr1 Rat, ALF, carbon tetrachloride –  ↔ Lower intestine, WB

↑ 3.4-fold digoxin absorption in vivo,

↓ 1.7-fold digoxin exsorption in everted intestinal sac

 [29]
 Abcg2/Bcrp Rat, ALF, thioacetamide –  ↔ Intestine, WB – [30]
 Abcc2/Mrp2 Rat, ALF, carbon tetrachloride – ↓ 2.4-fold jejunum, WB ↓ 3.3-fold, DNP-GSH transport in everted intestinal sac [31]
Cholestasis
 Abcb1a/Mdr1a Mice C57BL/6, BDL  ↔ , Ileum, WB [33]
 Abcg2/Bcrp Mice C57BL/6, BDL ↑ 1.6-fold, ileum, WB [33]
 Slc10a2/Asbt Mice C57BL/6, BDL  ↔ , Ileum, WB [33]
 Slc51a/OSTα Mice C57BL/6, BDL ↓ 1.7-fold, ileum, WB [33]
 Slc51b/Ostβ Mice C57BL/6, BDL ↓ 5.0-fold, ileum, WB [33]
Hyperthyroidism
 ABCB1/P-gp Caco2, T4 ↑ 5.5-fold, RT-PCR ↑ WB [35]
 ABCB1/P-gp LS180V, T4 ↑ 25.0-fold, RT-PCR [35]
 ABCB1/P-gp Caco2, T3 ↑ 10.0-fold, cPCR ↑ 2.5-fold, WB ↑ Tenfold transcellular transport, digoxin [34]
 mdr1a/mdr1b Rat, T4  ↔ Jejunum, ileum, cPCR  ↔ Jejunum, ileum, WB – [36]
 mdr1a/mdr1b Rat, T4 (8 µg/kg, p.o., 3 weeks)

↑ 2.0-fold,

 ↔ Jejunum,

 ↔ Ileum, RT-PCR

↑ 2.0-fold,

 ↔ Jejunum,

 ↔ Ileum, WB

 ↔ PK, cyclosporin A (10 mg/kg, i.v.)

↓ Fivefold AUC, cyclosporin A (10 mg/kg, p.o.)

 [37]
 ABCB1/P-gp Human (immunotherapy patients), T4 (100 µg, p.o., over 3 months) – – Significant ↓ in cyclosporin A (p.o.) blood concentrations [37]
 ABCB1/P-gp Human (volunteers), T4 (200 µg, p.o., 17 days) ↑ 1.4-fold, duodenum, cPCR ↑ 3.8-fold, duodenum, ICH  ↔ PK, talinolol (30 mg i.v., 100 mg, p.o.) [38]
 SLC15A1/PEPT1 Caco2, T3 ↓ 4.0-fold, cPCR ↓ 3.5-fold, WB ↓ Twofold Vmax, [14C]glycylsarcosine [39]
 Slc15a1/Pept1 Rat, T4 ↓ 1.4-fold, cPCR ↓ 1.4-fold, WB

↓ 1.2-fold [14C]glycylsarcosine transport, intestinal loop

↓ 1.9-fold Vmax of [14C]glycylsarcosine

 [40]
Hyperparathyroidism
 ABCG2/BCRP Caco2, PTH (1–34)  ↔ RT-PCR ↓ 1.3-fold, plasma membrane, WB, ICH, FC – [41]
 Abcg2/Bcrp Rat, SHPT –

 ↔ Tissue homogenate, intestine, WB

↓, Plasma membrane, intestine, WB

 – [41]
Cushing syndrome (iatrogenic)
 ABCB1/P-gp Rat, dexamethasone ↓ 2.0-fold, intestine, qPCR ↓ 1.3-fold, intestine, WB – [32]
 ABCC4/MRP4 HT-29, prednisone ↑ 14-fold, RT-PCR – – [42]
 ABCC4/MRP4 HT-29, hydrocortisone  ↔ , RT-PCR – – [42]
Diabetes mellitus
 ABCB1/P-gp Mice ddY, STZ – ↓ 2.0-fold, ileum, WB ↓ 1.3-fold Rho123 excreting activity [44]
 ABCB1/P-gp Mice ddY, STZ –

↓ 2.5-fold, duodenum

↓ 3.0-fold, jejunum

↓ 1.7-fold, ileum, WB

 – [43]
 ABCB1/P-gp Mice ddY, MSG

 ↔ Duodenum, ileum;

↑ 2.2-fold, jejunum, WB

 [43]
 ABCB1/P-gp Human, diabetes mellitus t.2  ↔ Duodenum, RT-PCR – – [45]
 ABCG2/BCRP Human, diabetes mellitus t.2  ↔ Duodenum, RT-PCR – – [45]
 SLC15A1/PEPT1 Caco2, insulin  ↔ cPCR ↑ 1.8-fold, membrane, WB ↑ 1.8-fold glycylglutamine transport [46]
 SLCO2B1/OATP2B1 Human, diabetes mellitus t.2 ↑ 1.3-fold, duodenum, RT-PCR – – [45]
Obesity
 ABCB1/P-gp Rat, high-fat diet – ↓ 1.2-fold, intestine, WB ↑ 1.2-fold nelfinavir bioavailability [47]
 ABCB1/P-gp Human, obese – 1.22 ± 0.37 fmol/μg protein, jejunum (LC–MS/MS) – [48]
 ABCC1/MRP1 Human, obese – 0.58 ± 0.20 fmol/μg protein, jejunum (LC–MS/MS) – [49]
 ABCC2/MRP2 Human, obese – 0.12 ± 0.04 fmol/μg protein, jejunum (LC–MS/MS) – [48]
 ABCC3/MRP3 Human, obese – 1.9 ± 0.74 fmol/μg protein (LC–MS/MS) – [48]
 ABCC4/MRP4 Human, obese – 0.31 ± 0.11 fmol/μg protein, jejunum (LC–MS/MS) – [49]
 ABCC5/MRP5 Human, obese – 0.05 ± 0.02 fmol/μg protein, jejunum (LC–MS/MS) – [49]
 ABCC6/MRP6 Human, obese – 0.30 ± 0.11 fmol/μg protein, jejunum (LC–MS/MS) – [49]
 ABCG2/BCRP Human, obese – 1.25 ± 0.54fmol/μg protein, jejunum (LC–MS/MS) – [49]
 SLC7A8/LAT2 Human, obese – 5.09 ± 1.00 fmol/μg protein, jejunum (LC–MS/MS) – [49]
 SLC15A1/PEPT1 Caco2, leptin  ↔ cPCR

↑ 2.2-fold, membrane

↓ 2.0-fold, intracellular, WB

↑ 3.0-fold glycylsarcosine transport

↑ 2.2-fold cephalexin transport

 [50]
 Slc15a1/Pept1 Rat, leptin – – ↑ 1.5-fold cephalexin transport [50]
 SLC15A1/PEPT1 Human, obese – 1.60 ± 0.71 fmol/μg protein, jejunum (LC–MS/MS) – [49]
 SLC16A1/MCT1 Human, obese – 1.85 ± 0.63 fmol/μg protein, jejunum (LC–MS/MS) – [49]
 SLC16A4/MCT4 Human, obese – 0.47 ± 0.10 fmol/μg protein, jejunum (LC–MS/MS) – [49]
 SLC22A4/OCTN1 Human, obese – 0.08 ± 0.01 fmol/μg protein, jejunum (LC–MS/MS) – [49]
 SLC28A2/CNT2 Human, obese – 0.84 ± 0.52 fmol/μg protein, jejunum (LC–MS/MS) – [49]
 SLC51A/OSTα Human, obese – 4.45 ± 1.35 fmol/μg protein, jejunum (LC–MS/MS) – [49]
 SLC51B/OSTβ Human, obese – 3.87 ± 1.02 fmol/μg protein, jejunum (LC–MS/MS) – [49]
 SLCO2A1/OATP2A1 Human, obese – 0.11 ± 0.05 fmol/μg protein, jejunum (LC–MS/MS) – [49]
 SLCO2B1/OATP2B1 Human, obese – 0.54 ± 0.13 fmol/μg protein, jejunum (LC–MS/MS) – [49]
General inflammation
 ABCB1/P-gp Caco2, TNF-α, IFN-ɣ

↓ 2.0-fold, TNF-α

↑ 2.5-fold IFN-ɣ, cPCR

 ↑ 1.5-fold IFN-ɣ (24 h), WB

↓ Rhodamine 123 transport, TNF-α

 ↔ Rhodamine 123 transport, IFN-ɣ

 [51]
 mdr1a/P-gp Rat, LPS

↓ 2.0-fold, duodenum

↓ 2.0-fold, jejunum

↓ 2.0-fold, ileum

↓ 2.0-fold, colon, RT-PCR

 – ↓ 1.8-fold AUC0–90 min, digoxin, Ussig chamber [53]
 mdr1a/P-gp Rat, adjuvant arthritis  ↔ (RT-PCR) – – [52]
 Abcc2/mrp2 Rat, LPS

↓ 2.0-fold, jejumum,

RT-PCR

 – ↓ 2.7-fold AUC0–90 min, 5-carboxyfluorescein, Ussig chamber [53]
 Abcc3/mrp3 Rat, LPS  ↔ RT-PCR – – [53]
 ABCC4/MRP4 HT-29, TNF-α, LPS

↑ Tenfold, TNF-α

↓ 3.3-fold, LPS, RT-PCR

 – – [42]
 ABCC4/MRP4 Human, intestinal tuberculosis ↓ 3.7-fold, RT-PCR – – [42]
 oatp1a1, oatp1b2, oatp2b1, oatp4a1, oat2, oat3, oct1, bsep, mrp1, mrp3, mrp6 Rat, adjuvant arthritis  ↔ RT-PCR – – [52]
Inflammatory bowel disease
 ABCB1/P-gp Human, UC ↓ 2.9-fold, colon, qRT-PCR  ↔ Colon, LC–MS/MS – [55]
 ABCB1/P-gp Human, IBD

 ↔ Colon (CD),

↓ 5.9-fold, colon (UC)

qRT-PCR

 – – [56]
 ABCB1/P-gp Human, UC ↓ 3.0-fold, sigmoid, qRT-PCR ↓ 7.8-fold, sigmoid, WB – [59]
 ABCB1/P-gp Human, UC ↓ 2.7-fold, colon, qRT-PCR ↓ 6.7-fold, colon, ICH – [58]
 ABCB1/P-gp Human, UC

↓ 1.2-fold, colon,

↓ 1.5-fold, rectum, qRT-PCR

 ↓ Colon, WB – [54]
 ABCB1/P-gp Human, UC –

↑ 1.9-fold, colon, CD

↑ 1.4-fold, colon, UC, ICH

 – [57]
 ABCC1/MRP1 Human, UC ↑ 1.6-fold, colon, qRT-PCR  ↔ Colon, LC–MS/MS – [55]
 ABCC2/MRP2 Human, UC ↑ 1.8-fold, sigmoid, qRT-PCR – – [59]
 ABCC2/MRP2 Human, UC  ↔ Colon, qRT-PCR – – [54]
 ABCC3/MRP3 Human, UC  ↔ Colon, qRT-PCR  ↔ Colon, LC–MS/MS – [55]
 ABCC3/MRP3 Human, IBD

 ↔ Colon (CD),

↓ 2.0-fold, colon (UC), qRT-PCR

 – – [56]
 ABCC4/MRP4 Human, UC ↑ 1.6-fold, colon, qRT-PCR  ↔ Colon, LC–MS/MS – [55]
 ABCC4/MRP4 Human, IBD

↓ 1.7-fold, colon (UC)

qRT-PCR

 – – [56]
 ABCC4/MRP4 Human, UC ↓ 4.0-fold, colon, qRT-PCR – – [42]
 ABCG2/BCRP Human, UC ↓ 5.6-fold, colon, qRT-PCR BLQ – [55]
 ABCG2/BCRP Human, UC ↓ 1.8-fold, colon (CD), qRT-PCR – – [56]
 ABCG2/BCRP Human, UC ↓ 2.8-fold, colon, qRT-PCR ↓ 2.9-fold, colon, ICH – [58]
 ABCG2/BCRP Human, UC

↓ 1.1-fold, colon,

↓ 1.2-fold, rectum, qRT-PCR

 ↓ Colon, WB – [54]
 ABCG2/BCRP Human, UC ↓ 1.5-fold, sigmoid, qRT-PCR – – [59]
 SLC10A2/ASBT Human, UC ↓ 2.8-fold, colon (CD), qRT-PCR – – [56]
 SLC15A1/PEPT1 Human, IBD  ↔ (CD), qRT-PCR – – [67]
 SLC15A1/PEPT1 Human, UC  ↔ Colon, qRT-PCR BLQ, LC–MS/MS – [55]
 SLC16A1/MCT1 Human, IBD ↓ 2.0-fold, colon, qRT-PCR

↓ 3.9-fold, colon,

LC–MS/MS

 [55]
 SLC22A3/OCT3 Human, IBD ↓ 4.3-fold, colon, qRT-PCR BLQ, LC–MS/MS [55]
 SLC22A4/OCTN1 Human, IBD  ↔ Ileum (CD), qRT-PCR – – [67]
 SLC22A4/OCTN1 Human, IBD –  ↔ Ileum, colon (CD), (WB)  ↔ Carnitine transport (CD) [68]
 SLC22A5/OCTN2 Human, IBD ↓ 50.0-fold (CD), ileum, qRT-PCR, – – [67]
 SLC22A5/OCTN2 Human, IBD –  ↔ Ileum, colon (CD), (WB)  ↔ Carnitine transport (CD) [68]
 SLC22A5/OCTN2 Human, UC  ↔ Colon, qRT-PCR BLQ, LC–MS/MS – [55]
 SLC28A2/CNT2 Human, IBD

 ↔ Ileum (CD),

qRT-PCR

 – – [67]
 SLC29A1/ENT1 Human, IBD ↑ 2.5-fold (CD), qRT-PCR – – [67]
 SLC29A2/ENT2 Human, IBD ↑ Fourfold (CD), qRT-PCR – – [67]
 SLC51A/OSTα Human, IBD

 ↔ Colon (CD),

↓ 5.0-fold, colon (UC)

qRT-PCR

 – – [56]
 SLC51B/OSTβ Human, IBD

 ↔ Colon (CD),

↓ 3.4-fold, colon (UC)

qRT-PCR

 – – [56]
 SLCO1B1/OATP1B1 Human, UC ↑ 1.7-fold, sigmoid, qRT-PCR – – [59]
 SLCO1B3/OATP1B3 Human, UC ↑ 15.8-fold, sigmoid, qRT-PCR – – [59]
 SLCO2B1/OATP2B1 Human, IBD ↑ Sevenfold (CD), ileum, qRT-PCR – – [67]
 SLCO4A1/OATP4A1 Human, IBD ↑ Fourfold (CD), ↔ (UC), ileum, qRT-PCR – – [67]
Coeliac disease
 ABCB1/P-gp Human, pediatric

↑ 12.0-fold (treated),

↑7.0-fold (untreated), qRT-PCR

 – – [69]
Alzheimer disease
 Abcc2/mrp2 Mouse APP/PS1 – ↑ 2.3-fold, small intestine, QTAP – [70]
 Slc16a1/mct1 Mouse APP/PS1 – ↓ 1.9-fold, small intestine, QTAP – [70]
 Slc7a8/lat2 Mouse APP/PS1 – ↓ 2.0-fold, small intestine, QTAP – [70]

ALF acute liver failure, ARF acute renal failure, BDL bile duct ligation, BLQ below quantification range, CD Crohn disease, CDF 5-(and-6)-carboxy-2-,7-dichlorofluorescein, CMPF 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid, IS indoxyl sulfate, cPCR competitive PCR, CRF chronic renal failure, DNP-GSH 2,4-dinitrophenyl-S-glutathione, FC flow cytometry, IBD inflammatory bowel disease, ICH immunohistochemistry, LPS lipopolysaccharide, MGS monosodium glutamate, PK pharmacokinetics, PTH parathyroid hormone, QTAP quantitative targeted absolute proteomics, SHPT secondary parathyroidism, STZ streptozotocin, T3 3,5,3′-L-triiodothyronine, T4 levothyroxine, UC ulcerative colitis, WB Western blot