DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

Table 5–4
ABC Transporters Involved in Drug Absorption, Distribution, and Excretion Processes (Continued)
TRANSPORTER TISSUE PHYSIOLOGICAL
NAME DISTRIBUTION FUNCTION SUBSTRATES
MRP4 Ubiquitous ? Characteristics: Nucleotide analogs
(ABCC4) (Kidney, Anticancer drugs: 6-mercaptopurine, methotrexate
Prostate, Lung,
Glucuronide conjugates: estradiol-17-D-glucuronide
Muscle, Pancreas,
Sulfate conjugates: dehydroepiandrosterone sulfate
Testis, Ovary,
Cyclic nucleotides: cAMP, cGMP
Bladder,
Diuretics: furosemide, trichlormethiazide
Gallbladder,
BBB, BCSFB)
Antiviral drugs: adefovir, tenofovir
Antibiotics: cefazolin, ceftizoxime
Others: folate, leucovorin, taurocholate (with GSH)
MRP5 Ubiquitous ? Characteristics: Nucleotide analogs
(ABCC5)
Anticancer drugs: 6-mercaptopurine
Cyclic nucleotides: cAMP, cGMP
HIV protease inhibitors: adefovir
MRP6 Liver ? Anticancer drugs: doxorubicin*, etoposide*
(ABCC6) Kidney Glutathione conjugates: leukotriene C 4
Other: BQ-123 (cyclic peptide)
BCRP Liver Normal heme Anticancer drugs: methotrexate, mitoxantrone,
(MXR) Intestine metabolism/ camptothecins SN-38, topotecan, imatinib
(ABCG2) BBB transport during
maturation of
erythrocytes?
Glucuronide conjugates: 4-methylumbelliferone
glucuronide, estradiol-17-D-glucuronide
Sulfate conjugates: dehydroepiandrosterone sulfate,
estrone-3-sulfate
Antibiotics: nitrofurantoin, fluoroquinolones
Statins: pitavastatin, rosuvastatin
Others: cholesterol, estradiol, dantrolene, prazosin,
sulfasalazine, phytoestrogens, PhIP, pheophorbide A
MDR3 Liver Excretion of Characteristics: Phospholipids
(ABCB4)
phospholipids
into bile
BSEP Liver Excretion of bile Characteristics: Bile salts
(ABCB11)
salts into bile
ABCG5 and Liver Excretion of plant Characteristics: Plant sterols
ABCG8 Intestine sterols into bile
and intestinal
lumen
Representative substrates and cytotoxic drugs with increased resistance (*) are included in this table (cytotoxicity with increased resistance is usually
caused by the decreased accumulation of the drugs). Although MDR3 (ABCB4), BSEP (ABCB11), ABCG5 and ABCG8 are not directly involved in
drug disposition, inhibition of these physiologically important ABC transporters will lead to unfavorable side effects.
BBB, blood-brain barrier; BTB, blood-testis barrier; BPB, blood-placental barrier; BCSFB, blood-cerebrospinal fluid barrier.
MRP4 accepts negatively charged molecules, including cytotoxic
compounds (e.g., 6-mercaptopurine and methotrexate), cyclic
nucleotides, antiviral drugs (e.g., adefovir and tenofovir), diuretics
(e.g., furosemide and trichlorothiazide), and cephalosporins (e.g.,
ceftizoxime and cefazolin). Glutathione enables MRP4 to accept taurocholate
and leukotriene B 4
.
MRP5 has a narrower substrate specificity and accepts
nucleotide analog and clinically important anti–human immunodeficiency
virus (HIV) drugs. Although some transport substrates have
been identified for MRP6, no physiologically important endogenous
substrates have been identified that explain the mechanism of the
MRP6-associated disease, pseudoxanthoma.