Biomedical Engineering Reference
In-Depth Information
TABLE 15.2. Comparison of the Substrate Selectivities of hOAT1, hOAT2, hOAT3,
hOAT4, hOCT1, and hOCT2, as Determined in Stable Transfected S
2
Cells
Uptake
K
m
(
μ
M) via:
Labeled Compound
hOAT1
hOAT2
hOAT3
hOAT4
hOCT1
hOCT2
[
14
C]TEA
−
−
−
−
+
+
[
14
C]PAH
+
+
+
+
−
−
[
14
C]Glutarate
+
+
+
+
−
−
[
3
H]Estrone sulfate
+
+
+
+
−
−
[
14
C]Urate
+
−
+
+
−
−
[
14
C]Succinate
+
−
−
+
−
−
[
14
C]Azidothymidine
+
(45.9)
+
(26.8)
+
(145.1)
+
(151.8)
-
-
[
3
H]Acyclovir
+
(342.3)
−
−
−
+
(151.2)
−
[
3
H]Ganciclovir
+
(895.5)
−
−
−
+
(516.2)
−
[
3
H]Valaciclovir
−
−
+
−
−
−
[
3
H]PGE
2
+
+
+
+
+
+
[
3
H]PGF
2
+
+
+
+
+
+
[
14
H]Indomethacin
+
−
−
−
−
−
[
14
C]Salicylate
+
+
+
−
−
−
[
3
H]Cimetidine
+
−
+
−
+
−
[
3
H]Tetracycline
+
+
+
+
−
−
[
3
H]Methotrexate
+
−
+
−
−
−
[
3
H]cGMP
+
−
+
−
−
−
[
3
H]Ochratoxin A
+
−
+
+
−
−
[
3
H]DHEAS
−
−
+
+
−
−
Source
: 13,15,19,27,33,35-37,40,45,46,49,51,160 and unpublished observation (Anzai and Endou).
observed in S
2
-hOAT1 and S
2
-hOCT1. In contrast, uptake of valacyclovir, L-valyl
ester of ACV, was observed only in S
2
-hOAT3. On the other hand, AZT uptake was
observed in S
2
-hOAT1, S
2
-hOAT2, S
2
-hOAT3, and S
2
-OAT4.
15.5. MISCELLANEOUS ASPECTS OF RENAL DRUG TRANSPORTERS
15.5.1. Transporter-Mediated Drug-Drug Interactions
Drugs present in plasma could affect the transport of these drugs individually while
mutually influencing the pharmacokinetics of the drugs. A notable example is the con-
comitant use of probenecid and penicillin G; the half-life of penicillin G is prolonged
significantly when combined with probenecid compared with when it is adminis-
tered alone. It has also been reported that methotrexate (MTX) administration with
acidic drugs, such as NSAIDs, and
-lactam antibiotics, causes a severe suppression
of bone marrow. NSAIDs and
-lactam antibiotics inhibit the tubular secretion of
MTX, thereby reducing its renal clearance. As a consequence, unwanted side effects,
such as bone marrow suppression, could occur as a result of the increase in plasma
MTX levels.
46
,
168
These phenomena can be explained at the level of OAT1 and OAT3.
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