A double-blind, randomized, placebo and positive-controlled study in healthy volunteers to evaluate pharmacokinetic and pharmacodynamic properties of multiple oral doses of cetagliptin
© 2021 British Pharmacological Society..
AIMS: This study investigated the pharmacokinetics and pharmacodynamics properties, safety and tolerability of cetagliptin.
METHODS: Forty-eight healthy subjects were enrolled in this study. Three cohorts were investigated in sequential order: 50, 100 and 200 mg cetagliptin. Positive control (sitagliptin 100 mg) was designed as open label. Blood samples were collected and analysed for pharmacokinetic and pharmacodynamic properties. Safety and tolerability were assessed throughout the study.
RESULTS: Following multiple oral doses, cetagliptin was rapidly absorbed and reached peak plasma concentrations after approximately 1.0-1.5 hours. Plasma cetagliptin concentrations increased at a rate greater than dose. Accumulation of cetagliptin was modest, and steady state was generally achieved at day 5. Doses ≥50 mg of cetagliptin administered once daily will result in sustained dipeptidyl peptidase-4 (DPP-4) inhibition (≥80%). The plasma concentration giving 50% of maximum drug effect of DPP-4 inhibition for cetagliptin (5.29 ng/mL) was lower than that of sitagliptin (7.03 ng/mL). Active glucagon-like-1 peptide (GLP-1) concentrations were significantly increased in the cetagliptin groups by 2.3- to 3.1-fold at day 1 and 3.1- to 3.6-fold at steady state compared with that of placebo, and active GLP-1 concentrations were increased with increasing dose. Compared with sitagliptin, doses ≥100 mg once daily of cetagliptin produced postprandial increases in active GLP-1 level and induced to long-lasting glucose-lowering efficacy. Cetagliptin was well tolerated across all doses studied.
CONCLUSION: Cetagliptin demonstrates the great potential for treatment with type 2 diabetes patients based on the inhibition of DPP-4, the increase in GLP-1 and insulin, the decrease in glucose, and might be more effective in DPP-4 inhibition than sitagliptin.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:88 |
|---|---|
| Enthalten in: |
British journal of clinical pharmacology - 88(2022), 6 vom: 29. Juni, Seite 2946-2958 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Lu, Jinmiao [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 17.05.2022 Date Revised 26.06.2022 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1111/bcp.15209 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM335014259 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM335014259 | ||
| 003 | DE-627 | ||
| 005 | 20231225224920.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1111/bcp.15209 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1116.xml |
| 035 | |a (DE-627)NLM335014259 | ||
| 035 | |a (NLM)34965609 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Lu, Jinmiao |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A double-blind, randomized, placebo and positive-controlled study in healthy volunteers to evaluate pharmacokinetic and pharmacodynamic properties of multiple oral doses of cetagliptin |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 17.05.2022 | ||
| 500 | |a Date Revised 26.06.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021 British Pharmacological Society. | ||
| 520 | |a AIMS: This study investigated the pharmacokinetics and pharmacodynamics properties, safety and tolerability of cetagliptin | ||
| 520 | |a METHODS: Forty-eight healthy subjects were enrolled in this study. Three cohorts were investigated in sequential order: 50, 100 and 200 mg cetagliptin. Positive control (sitagliptin 100 mg) was designed as open label. Blood samples were collected and analysed for pharmacokinetic and pharmacodynamic properties. Safety and tolerability were assessed throughout the study | ||
| 520 | |a RESULTS: Following multiple oral doses, cetagliptin was rapidly absorbed and reached peak plasma concentrations after approximately 1.0-1.5 hours. Plasma cetagliptin concentrations increased at a rate greater than dose. Accumulation of cetagliptin was modest, and steady state was generally achieved at day 5. Doses ≥50 mg of cetagliptin administered once daily will result in sustained dipeptidyl peptidase-4 (DPP-4) inhibition (≥80%). The plasma concentration giving 50% of maximum drug effect of DPP-4 inhibition for cetagliptin (5.29 ng/mL) was lower than that of sitagliptin (7.03 ng/mL). Active glucagon-like-1 peptide (GLP-1) concentrations were significantly increased in the cetagliptin groups by 2.3- to 3.1-fold at day 1 and 3.1- to 3.6-fold at steady state compared with that of placebo, and active GLP-1 concentrations were increased with increasing dose. Compared with sitagliptin, doses ≥100 mg once daily of cetagliptin produced postprandial increases in active GLP-1 level and induced to long-lasting glucose-lowering efficacy. Cetagliptin was well tolerated across all doses studied | ||
| 520 | |a CONCLUSION: Cetagliptin demonstrates the great potential for treatment with type 2 diabetes patients based on the inhibition of DPP-4, the increase in GLP-1 and insulin, the decrease in glucose, and might be more effective in DPP-4 inhibition than sitagliptin | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a cetagliptin | |
| 650 | 4 | |a dipeptidyl peptidase-4 | |
| 650 | 4 | |a pharmacodynamics | |
| 650 | 4 | |a pharmacokinetics | |
| 650 | 7 | |a Dipeptidyl-Peptidase IV Inhibitors |2 NLM | |
| 650 | 7 | |a Hypoglycemic Agents |2 NLM | |
| 650 | 7 | |a Glucagon-Like Peptide 1 |2 NLM | |
| 650 | 7 | |a 89750-14-1 |2 NLM | |
| 650 | 7 | |a Glucose |2 NLM | |
| 650 | 7 | |a IY9XDZ35W2 |2 NLM | |
| 650 | 7 | |a Sitagliptin Phosphate |2 NLM | |
| 650 | 7 | |a TS63EW8X6F |2 NLM | |
| 700 | 1 | |a Wang, Lu |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Sufeng |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Chen |e verfasserin |4 aut | |
| 700 | 1 | |a Xie, Lijun |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Juan |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Dong |e verfasserin |4 aut | |
| 700 | 1 | |a Tian, Xusheng |e verfasserin |4 aut | |
| 700 | 1 | |a Xie, Daosheng |e verfasserin |4 aut | |
| 700 | 1 | |a Ding, Juping |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Tong |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Qiang |e verfasserin |4 aut | |
| 700 | 1 | |a Ding, Jinsong |e verfasserin |4 aut | |
| 700 | 1 | |a Shao, Feng |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t British journal of clinical pharmacology |d 1974 |g 88(2022), 6 vom: 29. Juni, Seite 2946-2958 |w (DE-627)NLM000097799 |x 1365-2125 |7 nnns |
| 773 | 1 | 8 | |g volume:88 |g year:2022 |g number:6 |g day:29 |g month:06 |g pages:2946-2958 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1111/bcp.15209 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 88 |j 2022 |e 6 |b 29 |c 06 |h 2946-2958 | ||