Effects of food and ethnicity on the pharmacokinetics of venadaparib, a next-generation PARP inhibitor, in healthy Korean, Caucasian, and Chinese male subjects.
Aim: Venadaparib is a next-generation poly(ADP-ribose) polymerase inhibitor under development for treating gastric cancer. This study aimed to evaluate the effects of food and ethnicity on the pharmacokinetics (PKs) and safety of venadaparib after a single oral administration in healthy Korean, Cauc...
| Publicado en: | Investigational New Drugs Vol. 42; no. 1; pp. 80 - 89 |
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| Autores principales: | , , , , , , , , , |
| Formato: | research tables/charts randomized controlled trial Journal Article |
| Publicado: |
Springer Nature
Feb2024
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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=175636726&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 175636726 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 01676997 OH2 jtl: Investigational New Drugs issn: 01676997 maglogo: N pubinfo: dt: Feb2024 vid: 42 iid: 1 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 175636726 174230156 175636726 175636726 10.1007/s10637-023-01405-z 175636726 ppf: 80 ppct: 9 formats: tig: atl: Effects of food and ethnicity on the pharmacokinetics of venadaparib, a next-generation PARP inhibitor, in healthy Korean, Caucasian, and Chinese male subjects. aug: au: Kim, Hyun Chul Yang, Eunsol Lee, Soyoung Oh, Jaeseong Lee, Myongjae Lee, ChaeEun Ha, Kyoung Soo Lee, Won Sik Jang, In-Jin Yu, Kyung-Sang affil: https://ror.org/04h9pn542 Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, 101, Daehak-ro, Jongno-gu, 03080, Seoul, Republic of Korea sug: subj: Enzyme Inhibitors Pharmacokinetics Patient Safety Administration, Oral Enzyme Inhibitors Administration and Dosage Koreans White Persons Chinese Persons Food Drug-Food Interactions Drug Tolerance Human Crossover Design Randomized Controlled Trials Random Assignment Male Fasting Blood Specimen Collection Confidence Intervals Comparative Studies Descriptive Statistics Meals Adult Middle Age South Korea Funding Source Adult: 19-44 years Middle Aged: 45-64 years Male ab: Aim: Venadaparib is a next-generation poly(ADP-ribose) polymerase inhibitor under development for treating gastric cancer. This study aimed to evaluate the effects of food and ethnicity on the pharmacokinetics (PKs) and safety of venadaparib after a single oral administration in healthy Korean, Caucasian, and Chinese male subjects. Methods: In this randomized, open-label, single-dose, two-sequence, two-period, and crossover study, Korean and Caucasian subjects received venadaparib 80 mg in each period (fasted or fed state) with a seven-day washout. In an open-label, single-dose study, Chinese subjects received venadaparib 80 mg only in the fasted state. Serial blood samples were collected up to 72 h post-dosing. Results: Twelve subjects from each ethnic group completed the study. The geometric mean ratios (90% confidence intervals) of the maximum plasma concentration (Cmax) and area under the plasma concentration-time curve from time zero to the last measurable time point (AUClast) of venadaparib for the fed to fasted state were 0.82 (0.7457–0.9094) and 1.02 (0.9088–1.1339) in Koreans, and 0.77 (0.6871–0.8609) and 0.96 (0.9017–1.0186) in Caucasians, respectively. No statistically significant differences were observed in Cmax (P-value = 0.45) or AUClast (P-value = 0.30) among the three ethnic groups. A single venadaparib dose was well-tolerated. Conclusion: The overall systemic exposure of venadaparib was not affected by the high-fat meal, despite delayed absorption with a decreased Cmax in the fed state. The PK profiles were comparable among the Korean, Caucasian, and Chinese subjects. A single venadaparib 80 mg dose was safe and well-tolerated in both fasted and fed states. 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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