Combination Oxylanthanum Carbonate and Tenapanor Lowers Urinary Phosphate Excretion in Rats.

Abstract

Background: This study evaluated the combined effects of oxylanthanum carbonate (OLC), an investigational phosphate binder, and tenapanor, an approved sodium/hydrogen exchanger 3 (NHE3) inhibitor that reduces paracellular phosphate absorption, on urinary phosphate excretion in rats on a high phosphorus diet.

Methods: Sixty-four male Sprague Dawley rats were randomized into eight groups: vehicle; tenapanor (0.15 mg/kg) only; OLC (0.75%, 1.5%, and 3%) only; and combination OLC (0.75%, 1.5%, and 3%) + tenapanor (0.15 mg/kg). Vehicle and tenapanor were dosed orally twice/day whereas OLC was incorporated into diets. We collected 24-hour urine samples to measure urinary phosphate excretion, a proxy for intestinal phosphate absorption efficiency. Primary analyses compared pooled results in the three OLC dose groups.

Results: In the tenapanor 0.15 mg/kg group, mean urinary phosphate excretion from Days 9 to 11 was 8.5 mg/day (12.5%) lower compared to the vehicle group. In the OLC alone groups, mean urinary phosphate excretion (pooled across the 0.75, 1.5, and 3% OLC dose groups) was 12 mg/day (17.7%) lower compared to the vehicle group. Compared to vehicle, urinary phosphate excretion was 28.0 mg/day (41.3%) lower in the combination OLC + tenapanor groups (p=0.016). Bliss model of independence assessing the statistical significance between observed and predicted results indicated that combination OLC + tenapanor was synergistic (p=0.009 for 0.75% OLC + tenapanor and p=0.010 for 1.5% OLC + tenapanor).

Conclusions: In summary, we demonstrated sizeable reductions in urinary phosphate excretion in response to OLC monotherapy and the most pronounced reductions in urinary phosphate excretion when using OLC in combination with tenapanor.