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

KEY POINTS

Combination therapy with oxylanthanum carbonate+tenapanor led to greater reductions in urinary phosphate excretion than either drug alone. We demonstrated dose-dependent and sizable reductions in urinary phosphate excretion in response to oxylanthanum carbonate monotherapy.

BACKGROUND

This study evaluated the combined effects of oxylanthanum carbonate (OLC), an investigational phosphate binder, and tenapanor, an approved sodium/hydrogen exchanger 3 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 per 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/d (12.5%) lower compared with 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 12.1 mg/d (17.7%) lower compared with the vehicle group. Compared with vehicle, urinary phosphate excretion was 28.1 mg/d (41.3%) lower in the combination OLC+tenapanor groups ( = 0.016). Bliss model of independence assessing the statistical significance between observed and predicted results indicated that combination OLC+tenapanor was synergistic ( = 0.009 for 0.75% OLC+tenapanor and = 0.010 for 1.5% OLC+tenapanor).

CONCLUSIONS

We demonstrated sizable 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.