Assessing the binding interaction of polystyrene sulfonate with amitriptyline in healthy volunteers: a cross-over...

Polystyrene sulfonate is used for binding potassium in patients with chronic kidney disease (CKD). Because of its binding properties, it can potentially bind other medications and thereby decrease their bioavailability and effectiveness. Amitriptyline, often used by CKD patients for neuropathic pain, shows significant binding to polystyrene sulfonate in vitro. The purpose of this study was to determine the effect of polystyrene sulfonate on the exposure of amitriptyline in vivo when taken concomitantly in healthy volunteers.

We performed a prospective cross-over study in nine healthy volunteers. Participants were 18 years of age or older, did not use any medication, and had no known allergy to amitriptyline or polystyrene sulfonate. Participants visited Deventer Teaching Hospital twice. Once they received a single dose of amitriptyline 50 mg and once they received a single dose of both polystyrene sulfonate 15 g and amitriptyline 50 mg taken concomitantly, with a wash out period of at least 1 week. After intake of the medication, six blood samples were collected, at 2, 3, 4, 5, 6, and 8 h. Blood samples were analysed to determine maximum concentration (Cmax) and area under the curve 0-8 h after intake (AUC_0-8 h). Difference in Cmax and AUC_0-8 h was analysed with a paired T-test or Wilcoxon signed rank test, depending on normality of the data. A p-value < 0.05 was considered statistically significant.

Of the nine participants included, eight participants completed both visits to the hospital. Mean maximum concentration (Cmax) of amitriptyline was 35.61 µg l^-1 (95% CI 27.90-43.33 µg l^-1) when taken alone, compared to 9.25 µg l^-1 (95% CI 6.59-11.92 µg l^-1) when taken with polystyrene sulfonate (p < 0.001). Mean AUC_0-8 h of amitriptyline was 168.20 µg × h l^-1 (95% CI 139.95-196.45 µg × h l^-1) when taken alone and 45.78 µg × h l^-1 (95% CI 30.20-61.36 µg × h l^-1) when taken with polystyrene sulfonate (p < 0.0001).

These results show a significant decrease in exposure of amitriptyline of approximately 75% when taken concomitantly with polystyrene sulfonate, thereby probably compromising therapy efficacy. Patients using both amitriptyline and polystyrene sulfonate should be informed to separate intake of these medications.

NL8539 (17 April 2020).