# Lack of Modulation of In Vivo Activity of Organic Anion Transporters 1 and 3 in Pregnancy Using Furosemide as a Probe

## TL;DR

This study found that the activity of two kidney transporters, OAT1 and OAT3, remains unchanged during pregnancy when tested with furosemide, a diuretic drug.

## Contribution

The study is the first to use furosemide as a probe to assess OAT1/3 activity in vivo during pregnancy.

## Key findings

- Pregnant women showed lower drug exposure and urinary excretion of furosemide compared to non-pregnant women.
- Clearance parameters indicated increased non-renal and overall clearance but no significant change in OAT1/3-mediated renal secretion.
- The results suggest that intestinal absorption, not kidney transporters, may be affected during pregnancy.

## Abstract

Pregnancy induces physiological changes that can alter drug disposition, yet little is known about their impact on renal transporters such as organic anion transporters 1 and 3 (OAT1/3). This study aimed to evaluate the in vivo activity of OAT1/3 during pregnancy using furosemide as a probe substrate. Twelve healthy non‐pregnant women and 10 healthy pregnant women, mostly in the third trimester, received a single 40‐mg oral dose of furosemide under fasting conditions. Serial blood and urine samples were collected for up to 24 h. Pharmacokinetic parameters were estimated by non‐compartmental analysis, including time to maximum plasma concentration (tmax), maximum plasma concentration (Cmax), area under the plasma concentration–time curve (AUC), amount excreted in urine (Ae), fraction excreted unchanged in urine (fe), unbound plasma fraction (fu), apparent clearance (CL/F), renal clearance (CLR), non‐renal clearance (CLNR), secretory clearance (CLSEC), and metabolic clearance via furosemide glucuronide formation (CLM). Compared with non‐pregnant women, pregnant women exhibited significantly lower exposure, Cmax, Ae, and fe values, while CL/F and CLNR were significantly increased. In contrast, no significant differences were observed for CLR and CLSEC, indicating preserved OAT1/3 activity. These findings suggest unchanged OAT1/3‐mediated renal secretory activity during pregnancy contrast with the published literature for other OAT1/3 substrates, which have, in most cases, reported an increase in OAT1/3 activity during pregnancy. Instead, the data raise the hypothesis that changes in intestinal absorption of furosemide, possibly influenced by gestational regulation of intestinal transporters, may contribute to the lower exposure.