Effect of grapefruit juice on the pharmacokinetics of tolvaptan, a non-peptide arginine vasopressin antagonist, in healthy subjects.
Purpose: Tolvaptan is a selective vasopressin V2 receptor antagonist that can be given orally once daily for treatment of clinically significant hypervolemic and euvolemic hyponatremia (US and Europe) or extracellular volume expansion despite taking other diuretics (Japan). In vitro studies indicate...
| Publicado en: | European Journal of Clinical Pharmacology Vol. 68; no. 2; pp. 207 - 212 |
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| Autores principales: | , , |
| Formato: | research tables/charts randomized controlled trial Journal Article |
| Publicado: |
Springer Nature
Feb2012
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=104626825&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 104626825 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00316970 NP9 jtl: European Journal of Clinical Pharmacology issn: 00316970 maglogo: N pubinfo: dt: Feb2012 vid: 68 iid: 2 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 104626825 70247451 10.1007/s00228-011-1106-4 NLM21853290 104626825 ppf: 207 ppct: 5 formats: fmt: @attributes: type: P tig: atl: Effect of grapefruit juice on the pharmacokinetics of tolvaptan, a non-peptide arginine vasopressin antagonist, in healthy subjects. aug: au: Shoaf, Susan Mallikaarjun, Suresh Bricmont, Patricia affil: Clinical Pharmacology, Otsuka Pharmaceutical Development & Commercialization, Inc., 2440 Research Boulevard Rockville 20850 USA sug: subj: Heterocyclic Compounds Pharmacokinetics Grapefruit Pharmacokinetics Fruit Juices Vasopressins Antagonists and Inhibitors Hyponatremia Drug Therapy Drug-Food Interactions Random Assignment Crossover Design Heterocyclic Compounds Administration and Dosage Heterocyclic Compounds Blood Biological Availability Human Male Female Adult Chromatography, High Pressure Liquid Mass Spectrometry Data Analysis Software Descriptive Statistics Analysis of Variance Confidence Intervals Heterocyclic Compounds Adverse Effects Heterocyclic Compounds Urine Funding Source Randomized Controlled Trials Adult: 19-44 years Male Female ab: Purpose: Tolvaptan is a selective vasopressin V2 receptor antagonist that can be given orally once daily for treatment of clinically significant hypervolemic and euvolemic hyponatremia (US and Europe) or extracellular volume expansion despite taking other diuretics (Japan). In vitro studies indicated that tolvaptan was a CYP3A4 substrate. Methods: A single-center, randomized, crossover trial of 60-mg tolvaptan with 240 mL of water or with 240 mL of reconstituted grapefruit juice (washout period of 72 h between doses) was conducted in 20 healthy subjects. Blood samples for tolvaptan plasma concentrations were obtained for 48 h postdose. Results: All subjects completed the trial. Following co-administration with grapefruit juice, tolvaptan concentrations were elevated compared with tolvaptan alone for only 16 h postdose; consequently, the mean elimination half-life of tolvaptan was unchanged, 5.7 vs 5.1 h respectively. The mean maximal plasma concentration (C) and the area under the curve (AUC) of tolvaptan were increased 1.86- and 1.56-fold respectively when co-administered with grapefruit juice. Conclusions: It appears that grapefruit juice increases the bioavailability of tolvaptan, but does not affect its systemic elimination. The adverse event profile was consistent with the aquaretic effect of tolvaptan as urinary frequency, thirst, and dry mouth were the most frequently reported events. 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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