Abstract: FR-PO219
In Vitro Evaluation of Drug-Drug Interactions of Patiromer With Common Renal and Cardiovascular Drugs
Session Information
- Pharmacology
November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Pharmacology (PharmacoKinetics‚ -Dynamics‚ -Genomics)
- 1900 Pharmacology (PharmacoKinetics‚ -Dynamics‚ -Genomics)
Authors
- Schmitt, Jörg Simon, Vifor Pharma Ltd, St Gallen, Switzerland, St Gallen, Switzerland
- Steck, Anna-Lena, Vifor Pharma Ltd, St Gallen, Switzerland, St Gallen, Switzerland
- Khoeiklang, Martin, Vifor Pharma Ltd, St Gallen, Switzerland, St Gallen, Switzerland
- Moreno Quinn, Carol Patricia, Vifor Pharma Ltd, St Gallen, Switzerland, St Gallen, Switzerland
- Kretz, Martin, Vifor Pharma Ltd, St Gallen, Switzerland, St Gallen, Switzerland
- Bauer, Michael, Vifor Pharma Ltd, St Gallen, Switzerland, St Gallen, Switzerland
- Li, Lingyun, Vifor Pharma Inc., Redwood City, Redwood City, California, United States
- Wilhelm, Maria, Vifor Pharma Ltd, St Gallen, Switzerland, St Gallen, Switzerland
Background
Patiromer (PAT) is a non-absorbed potassium binder approved for treatment of hyperkalemia (HK) and has the potential to bind off-target, positively charged molecules in the gastrointestinal tract (GIT), leading to drug–drug interactions (DDIs) with co-administered oral drugs. Generally, separation of administration by 3 hours between PAT and other oral medications is recommended. We sought to further extend the range of medications that can be administered simultaneously with PAT by evaluating drugs used to treat cardio-renal patients with hyperkalemia.
Methods
This study utilizes single- and gradient-pH (1.2, 4.5 and 6.8) in vitro models mimicking GIT passage to determine DDIs between PAT and 25 cardio-renal drugs. Resultant free test drug concentration was determined by liquid chromatography, and percentage recovery (mean [95% confidence interval]) was calculated from six replicates; <70% recovery with PAT compared with drug alone was deemed a significant DDI.
Results
At pH 1.2, <70% (mean [95% confidence interval]) recovery was observed with quinapril (68.0 [67.7–68.2]), telmisartan (9.9 [9.7–10.1]), losartan potassium (46.3 [45.9–46.7]), azilsartan (14.2 [12.8–15.5]), irbesartan (58.1 [57.0–59.2]), olmesartan medoxomil (58.9 [58.2–59.6]), carvedilol (1.3 [1.1–1.5]), nebivolol (5.5 [5.2–5.8]), finerenone (54.8 [54.0–55.6]) and torasemide (44.7 [44.4–45.1]). At pH 4.5, <70% recovery was observed with carvedilol, nebivolol and finerenone (5.4 [5.1–5.7], 15.8 [14.8–16.7], 69.6 [69.1–70.1], respectively), and at pH 6.8 with telmisartan (10.8 [10.5–11.1]), bisoprolol fumarate (67.6 [66.5–68.6]), carvedilol (1.6 [1.5–1.7]) and nebivolol (6.9 [6.1–7.6]). Binding was associated with charge and lipophilicity. In the gradient-pH model simulating overall GIT passage, >70% recovery of quinapril, losartan potassium, irbesartan, olmesartan medoxomil, azilsartan, finerenone and torasemide was observed.
Conclusion
Of the 25 drugs tested, 14 showed ≥70% recovery with PAT. 11 showed <70% recovery with PAT, mostly at pH 1.2. However, 7 drugs with DDIs at pH 1.2 showed no relevant interactions with patiromer at gradient pH, suggesting DDIs at low pH could be reversed as test drugs became neutral or negatively charged in the intestine, where most drugs are absorbed.
Funding
- Commercial Support –