AGE- AND GENDER-RELATED DIFFERENCES IN XENOBIOTIC TRANSPORTER EXPRESSION - Drug Transporters: Molecular Characterization and Role in Drug Disposition - page 597

TABLE 20.1. Hepatic Transporter Ontogeny Patterns
Fetal

Birth Early Middle Late

Function Transporters ( − 2) (0) (5-10) (15-23) (30 → )

Liver uptake Oatp1a1 ∗

Oatp1a4 ∗

Oatp1a6 ∗

Oatp1b2 ∗

Oatp2a1 ∗

Oatp2b1 ∗

Ent1 ∗ ∗

Ntcp ∗

∗

Oat2

∗

Oct1

Liver efflux into bile Mrp2 ∗

Mate1 ∗

Mate2 ∗

Mdr1b
Mdr2 ∗ ∗

Bcrp ∗

Bsep ∗

Abcg5 ∗ ∗

Abcg8 ∗ ∗

Liver efflux into blood Mrp3 ∗

Mrp4 ∗

Mrp6 ∗

Ost ∗

Ost ∗

∗ Approximately adult levels.

20.3.2. Renal Uptake from Blood

The kidney contains numerous transporters for the uptake of chemicals into proximal
tubule cells, efflux into filtrate, reabsorption from the filtrate, and efflux back into
blood (Figure 20.5). In kidney, organic anion transporters (Oats), in general, are most
important for uptake of organic anions from blood. 51 , 52 As noted in Figure 20.6, Oat1
and 3 mRNA in mouse kidney are less at birth than in adults. Oat1begins to increase at
30 days of age and reaches adult levels by 40 days of age. Oat1 exhibits gender differ-
ences in mRNA expression; higher expression is observed in kidneys of male mice at
30 days of age and older. Oat3 reaches adult levels of expression in mice at 35 days of
age. In rats, Oat3 matured at the youngest age, Oat1 at an intermediate age, and Oat2 at
a later age. 23 The expression of Oat1 is male-predominant in rat kidneys as in mice. 23 , 51
Oatp4c1 transports xenobiotics, such as digoxin, from blood into proximal tubule
cells. 53 Its expression is relatively constant from before birth until 2 weeks of age,
when it more than doubles, to adult levels. 17