Mechanism of triamterene transfer across the human placenta.
The diuretic, triamterene, had been regarded to be a drug which was actively transported by the placenta from fetus to mother. In the present study, the transfer of triamterene across the isolated perfused human placenta was examined. Placentas obtained at cesarean section were perfused for up to 2 hr from both maternal and fetal sides in either single-pass or recycling constant flow systems. In single-pass experiments, the placental clearance of triamterene (400 ng/ml) from mother to fetus or from fetus to mother was examined (n = 8). Antipyrine (20 micrograms/ml) and l-leucine (0.25 mM) were used as reference compounds. The transplacental clearance index (i.e., clearance relative to antipyrine clearance) of triamterene from mother to fetus (0.85 +/- 0.10) was similar to the clearance index from fetus to mother (0.74 +/- 0.08, P greater than .10), indicating rapid transfer across the placenta, but no active fetal to maternal transport. In contrast, the l-leucine clearance index from mother to fetus (0.62 +/- 0.05) was substantially greater than that from fetus to mother (0.27 +/- 0.03, P less than .01), consistent with active maternal to fetal transport. In recycling experiments (n = 5), with test compounds added in equal concentration to both maternal and fetal circuits, the equilibrium fetal/maternal perfusate concentration ratios were 1.41 +/- 0.02 for l-leucine and 0.98 +/- 0.01 for antipyrine. The slightly lower value for triamterene (0.92 +/- 0.02) probably reflected minor differences in protein binding between maternal and fetal circuits.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Medicine, Austin Hospital, Melbourne, Victoria, Australia.
M S
MS
Ching
M A
MA
Czuba
G W
GW
Mihaly
D J
DJ
Morgan
K M
KM
Hyman
J D
JD
Paull
R A
RA
Smallwood
D004232:Diuretics / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007930:Leucine / Q000493:pharmacokinetics; D008431:Maternal-Fetal Exchange; D010477:Perfusion; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D014223:Triamterene / Q000493:pharmacokinetics*
D004232:Diuretics; D007930:Leucine; D014223:Triamterene