Exploring co-dispensed drug use in patients on sevelamer or polystyrene sulfonate to identify potential novel binding interactions: a cross sectional in silico study

Laar, Inge R F van Berlo-van de; Prins-Can, I; Schuiling-Veninga, Catharina C M; Taxis, Kstja; Jansman, Frank G A

doi:10.1007/s11096-021-01355-7

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“…A previous study of our research group identified several new potential binding interactions with polystyrene sulfonate, based on their chemical structure, one of which was the tricyclic antidepressant amitriptyline. Amitriptyline is positively charged in the gastrointestinal tract and thereby susceptible to binding to the negatively charged polystyrene sulfonate [15]. Amitriptyline is usually used as an analgesic for neuropathic pain in patients with CKD and haemodialysis [16,17].…”

Section: Introductionmentioning

confidence: 99%

Assessing the binding interaction of polystyrene sulfonate with amitriptyline in healthy volunteers: a cross-over design — The BIND study

Prins-Can

Laar

Zeeman

et al. 2022

Eur J Clin Pharmacol

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Purpose 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. Methods 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. Results 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). Conclusion 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. Trial registration NL8539 (17 April 2020).

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Section: Introductionmentioning

confidence: 99%