Pharmacokinetics and pharmacodynamics of ticagrelor in subjects on hemodialysis and subjects with normal renal function.
Purpose: This single-dose, randomized, open-label, parallel-group, and crossover study assessed pharmacokinetics (PK), pharmacodynamics (PD), and safety of ticagrelor in subjects on hemodialysis versus healthy subjects.Methods: Hemodialysis subjects were randomized, receiving a single ticagrelor 90-...
| Published in: | European Journal of Clinical Pharmacology Vol. 74; no. 9; pp. 1141 - 1149 |
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| Main Authors: | , , , , , |
| Format: | research tables/charts randomized controlled trial Journal Article |
| Published: |
Springer Nature
Sep2018
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=131207664&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 131207664 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00316970 NP9 jtl: European Journal of Clinical Pharmacology issn: 00316970 maglogo: N pubinfo: dt: Sep2018 vid: 74 iid: 9 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 131207664 131207664 131207664 10.1007/s00228-018-2484-7 131207664 ppf: 1141 ppct: 8 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Pharmacokinetics and pharmacodynamics of ticagrelor in subjects on hemodialysis and subjects with normal renal function. aug: au: Teng, Renli Muldowney, Sharen Zhao, Yonggang Berg, Jolene Kay Lu, Jonathan Khan, Naeem D. affil: AstraZeneca, Gaithersburg, MD, USA sug: subj: Platelet Aggregation Inhibitors Pharmacokinetics Platelet Aggregation Inhibitors Pharmacodynamics Dialysis Patients Platelet Aggregation Inhibitors Administration and Dosage Patient Safety Kidney Metabolism Kidney Drug Effects Human Randomized Controlled Trials Crossover Design Creatine Blood Platelet Aggregation Inhibitors Blood ab: Purpose: This single-dose, randomized, open-label, parallel-group, and crossover study assessed pharmacokinetics (PK), pharmacodynamics (PD), and safety of ticagrelor in subjects on hemodialysis versus healthy subjects.Methods: Hemodialysis subjects were randomized, receiving a single ticagrelor 90-mg dose 1 day post-hemodialysis or just before hemodialysis, with an intervening washout of ≥ 7 days. Healthy subjects (creatinine clearance ≥ 90 mL/min) received a single ticagrelor 90-mg dose. PK, PD (P2Y12 reaction units [PRU], inhibition of platelet aggregation [IPA]), and safety were evaluated.Results: Twenty-seven subjects (14 hemodialysis, 13 healthy) received ticagrelor. The mean maximum plasma concentration (Cmax) and area under the plasma concentration curve from time zero to infinity (AUC0-∞) of ticagrelor were 598.4 ng/mL and 3256.1 ng·h/mL, respectively, in pre-hemodialysis subjects; 560.3 ng/mL and 3015.1 ng·h/mL, respectively, in post-hemodialysis subjects; and 370.8 ng/mL and 2188.8 ng·h/mL, respectively, in healthy subjects. Cmax and AUC0-∞ of AR-C124910XX, the active metabolite, were 152.3 ng/mL and 1144.2 ng·h/mL, respectively, in pre-hemodialysis subjects; 130.8 ng/mL and 1127.8 ng·h/mL, respectively, in post-hemodialysis subjects; and 111.7 ng/mL and 1000.4 ng·h/mL, respectively, in healthy subjects. Mean IPA time curves over 24 h post-dose were almost indistinguishable for all three treatments. The greatest reduction in mean PRU occurred approximately 2 h post-dose for all three treatments. No safety or tolerability issues were identified.Conclusion: Hemodialysis resulted in modestly higher exposure to ticagrelor and AR-C124910XX, with no clinically significant effect on PD or tolerability. Accordingly, no dose adjustment is required for hemodialysis patients. Timing of hemodialysis has little impact on ticagrelor PK, or the effect of ticagrelor on IPA. pubtype: Academic Journal doctype: research tables/charts randomized controlled trial Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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