Subtherapeutic serum quetiapine concentrations after absorption inhibition by binding resins: a case report

Hoge, R. H. L.; Arbouw, Maurits; Radstake, S. D. W. S.; Laar, I. R. van Berlo – van F. de

doi:10.1111/jcpt.12265

Cited by 5 publications

(14 citation statements)

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“…In vitro experiments, to assess binding to resins, have been described in literature before. 21 , 23 , 32 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 The sensitivity of in vitro studies for identifying compounds binding to resins is high, but the specificity may be low. 32 Studies confirming that in vitro binding is also clinically relevant in vivo have been described for different drug–resin combinations.…”

Section: Discussionmentioning

confidence: 99%

“… 32 Studies confirming that in vitro binding is also clinically relevant in vivo have been described for different drug–resin combinations. 21 , 22 , 32 , 39 , 40 , 42 , 43 However, there are also several studies in which in vitro binding could not be confirmed in vivo to the same extent. 32 , 34 , 36 , 41 , 44 , 45 , 46 This can be explained by the fact that drug absorption from the gastrointestinal tract is affected by many different factors such as absorptive surface area, pH, food effects, co‐medication, intestinal transit time, passive intestinal permeability, intestinal transporters, and enzymes that are not accounted for in vitro .…”

Section: Discussionmentioning

confidence: 99%

“…Clinical studies and case reports have shown that sevelamer binds to levothyroxine, ciprofloxacin, mycophenolic acid, tacrolimus, cyclosporine, vitamin D analogues, lipid soluble vitamins like vitamins A, E, and K, folic acid, quetiapine, furosemide, and levetiracetam. 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 For polystyrene sulfonate, binding interactions have been described with lithium, quetiapine, and levothyroxine. 21 , 22 , 23 CKD patients often use many different drugs (average of eight drugs a day), and the prevalence of potential drug–drug interactions in CKD patients is high (75%–91%).…”

Section: Introductionmentioning

confidence: 99%

“… 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 For polystyrene sulfonate, binding interactions have been described with lithium, quetiapine, and levothyroxine. 21 , 22 , 23 CKD patients often use many different drugs (average of eight drugs a day), and the prevalence of potential drug–drug interactions in CKD patients is high (75%–91%). 24 , 25 , 26 , 27 , 28 , 29 , 30 Therefore, probably more drug binding interactions with sevelamer and/or polystyrene sulfonate than already described in literature may be of clinical relevance.…”

Section: Introductionmentioning

confidence: 99%

“…3 Because of their binding properties, resins are known to bind other drugs in the gastrointestinal tract, decreasing their bioavailability and clinical effectiveness.Clinical studies and case reports have shown that sevelamer binds to levothyroxine, ciprofloxacin, mycophenolic acid, tacrolimus, cyclosporine, vitamin D analogues, lipid soluble vitamins like vitamins A, E, and K, folic acid, quetiapine, furosemide, and levetiracetam. [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] For polystyrene sulfonate, binding interactions have been described with lithium, quetiapine, and levothyroxine. [21][22][23] CKD patients often use many different drugs (average of eight drugs a day), and the prevalence of potential drug-drug…”

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confidence: 99%

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Binding interactions with sevelamer and polystyrene sulfonate in vitro

Laar

Prins-Can

Lange

et al. 2021

Pharmacology Res & Perspec

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This study explored the binding of 28 drugs, which were selected based on frequency of concomitant use and chemical properties, to sevelamer and polystyrene sulfonate in vitro . The relative binding was determined by dissolving the investigated drugs alone (=control), together with 800 mg of sevelamer and 15 g of polystyrene sulfonate at different pH levels (1.5, 5.5, and 7.4), respectively. After incubation at 37℃ and shaking for 60 min, the solutions were diluted and centrifuged, and the drug concentrations were quantified with validated analytical assays. The binding assays were performed in threefold. The mean relative binding (MRB) at each pH level was calculated, with a MRB >20% for at least one pH level to be considered as relevant binding. Fourteen and 23 potentially new binding interactions were identified with sevelamer and polystyrene sulfonate, respectively. These potentially new binding interactions have to be studied in vivo to assess their clinical relevance.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Binding interactions with sevelamer and polystyrene sulfonate in vitro

Laar

Prins-Can

Lange

et al. 2021

Pharmacology Res & Perspec

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

et al. 2021

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BackgroundSevelamer and polystyrene sulfonate are used for treating hyperphosphatemia and hyperkalaemia in chronic kidney disease patients. Because of their binding properties, these resins potentially bind other drugs in the gastrointestinal tract, thereby decreasing their bioavailability and clinical effectiveness. AimThe aim of this study was to explore co-dispensed drug use in patients on sevelamer or polystyrene sulfonate to identify potential novel binding interactions. MethodIn this in silico study, the 100 drugs most frequently co-dispensed with sevelamer/polystyrene sulfonate in the period 2000-2018 from the University Groningen IADB.nl database were extracted. Drugs dispensed to < 5% of patients, drugs not orally administered, drugs administered once daily before bedtime and drugs for which information on binding interactions with sevelamer or polystyrene was already available were excluded. The likelihood of an interaction (yes or no) of the included drugs was assessed based on pKa-and Log P values. For sevelamer, drugs with a pKa (acid) between 1.5 and 7.4 and or a Log P value > 2.0 were identi ed as potential interacting drug. For polystyrene sulfonate, drugs with a pKa (base) > 1.5 were identi ed as potential interacting drug. ResultsOf the top 100 drugs most frequently co-dispensed with sevelamer/polystyrene sulfonate, 22 and 27 potentially clinically relevant new interacting drugs were identi ed for sevelamer and polystyrene sulfonate respectively. ConclusionSeveral potentially relevant novel binding interactions for sevelamer and polystyrene sulfonate were identi ed based on dispensing data and assessment of chemical properties for which further interaction research is warranted. Impacts Of Findings On Practice StatementsSevelamer and polystyrene sulfonate, resins used to treat hyperphosphatemia and hyperkalaemia in chronic kidney disease patients, may bind other drugs in the gastrointestinal tract decreasing their bioavailability and clinical effectiveness For sevelamer, 22 potentially clinically relevant new interacting drugs were identi ed based on dispensing data and pKa-and Log P-values For polystyrene sulfonate, 27 potentially clinically relevant new interacting drugs were identi ed accordingly.Further in vitro and in vivo interaction research is necessary to con rm these ndings and to assess the clinical relevance

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Subtherapeutic serum quetiapine concentrations after absorption inhibition by binding resins: a case report

Abstract: Polystyrene sulfonate and sevelamer are able to bind quetiapine. Healthcare professionals should be aware of this potential drug-drug interaction as this could lead to antipsychotic treatment failure.

Cited by 5 publications

References 8 publications

Binding interactions with sevelamer and polystyrene sulfonate in vitro

Binding interactions with sevelamer and polystyrene sulfonate in vitro

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

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

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