Selection of the candidate compound at an early stage of new drug development: retrospective pharmacokinetic and metabolic evaluations of valsartan using common marmosets / Shogo Matsumoto, Shotaro Uehara, Hidetaka Kamimura, Naoki Cho, Hiroshi Ikeda, Satoshi Maeda, Kensuke Kagiyama, Atsunori Miyata, Hiroshi Suemizu, Kazumasa Fukasawa
Abstract Valsartan is an antihypertensive drug that was developed using common marmosets ( Callithrix jacchus ) in pivotal toxicity studies as a non-rodent species. The aim of the present study was to investigate the utility of marmosets in the candidate selection of this drug from a pharmacokinetic and metabolic viewpoint. Valsartan, as well as three other angiotensin II type-I receptor blockers, assumed as competitive candidates, were administered to common marmosets. Human pharmacokinetic parameters predicted by single-species allometric scaling and Wajima superposition suggested that valsartan may exhibit promising pharmacokinetic properties in humans. In vitro metabolic studies of valsartan using isolated rat, dog, marmoset, cynomolgus monkey, and human hepatocytes revealed that the marmoset was the most relevant animal species to humans presenting with the most abundant human metabolite, 4-hydroxyvalsartan. Oral administration of an elevated dose of valsartan to a common marmoset demonstrated that the level of 4-hydroxyvalsartan in the plasma was comparable to that in clinical practice and suggested that safety of the human metabolite might have been confirmed in the toxicity studies using common marmosets. These results suggest that common marmosets, the small, non-human primates, had been a suitable species for the development of valsartan.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:52 |
|---|---|
| Enthalten in: |
Xenobiotica - 52(2022), 6, Seite 613-624 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Matsumoto, Shogo [VerfasserIn] |
|---|
| Links: |
FID Access [lizenzpflichtig] |
|---|
| Themen: |
Allometry |
|---|
| Umfang: |
1 Online-Ressource (12 p) |
|---|
| doi: |
10.1080/00498254.2022.2127131 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
KFL011135859 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | KFL011135859 | ||
| 003 | DE-627 | ||
| 005 | 20230713210905.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 230609s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1080/00498254.2022.2127131 |2 doi | |
| 035 | |a (DE-627)KFL011135859 | ||
| 035 | |a (KFL)prod_LgpH_10.1080/00498254.2022.2127131 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 084 | |a PHARM |q DE-84 |2 fid | ||
| 100 | 1 | |a Matsumoto, Shogo |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Selection of the candidate compound at an early stage of new drug development: retrospective pharmacokinetic and metabolic evaluations of valsartan using common marmosets |c Shogo Matsumoto, Shotaro Uehara, Hidetaka Kamimura, Naoki Cho, Hiroshi Ikeda, Satoshi Maeda, Kensuke Kagiyama, Atsunori Miyata, Hiroshi Suemizu, Kazumasa Fukasawa |
| 264 | 1 | |c 2022 | |
| 300 | |a 1 Online-Ressource (12 p) | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 520 | |a Abstract Valsartan is an antihypertensive drug that was developed using common marmosets ( Callithrix jacchus ) in pivotal toxicity studies as a non-rodent species. The aim of the present study was to investigate the utility of marmosets in the candidate selection of this drug from a pharmacokinetic and metabolic viewpoint. Valsartan, as well as three other angiotensin II type-I receptor blockers, assumed as competitive candidates, were administered to common marmosets. Human pharmacokinetic parameters predicted by single-species allometric scaling and Wajima superposition suggested that valsartan may exhibit promising pharmacokinetic properties in humans. In vitro metabolic studies of valsartan using isolated rat, dog, marmoset, cynomolgus monkey, and human hepatocytes revealed that the marmoset was the most relevant animal species to humans presenting with the most abundant human metabolite, 4-hydroxyvalsartan. Oral administration of an elevated dose of valsartan to a common marmoset demonstrated that the level of 4-hydroxyvalsartan in the plasma was comparable to that in clinical practice and suggested that safety of the human metabolite might have been confirmed in the toxicity studies using common marmosets. These results suggest that common marmosets, the small, non-human primates, had been a suitable species for the development of valsartan | ||
| 653 | |a Allometry | ||
| 653 | |a common marmoset | ||
| 653 | |a compound optimisation | ||
| 653 | |a metabolic profile | ||
| 653 | |a MIST guidance | ||
| 653 | |a prediction | ||
| 653 | |a total clearance | ||
| 653 | |a volume of distribution | ||
| 700 | 1 | |a Uehara, Shotaro |e verfasserin |4 aut | |
| 700 | 1 | |a Kamimura, Hidetaka |e verfasserin |4 aut | |
| 700 | 1 | |a Cho, Naoki |e verfasserin |4 aut | |
| 700 | 1 | |a Ikeda, Hiroshi |e verfasserin |4 aut | |
| 700 | 1 | |a Maeda, Satoshi |e verfasserin |4 aut | |
| 700 | 1 | |a Kagiyama, Kensuke |e verfasserin |4 aut | |
| 700 | 1 | |a Miyata, Atsunori |e verfasserin |4 aut | |
| 700 | 1 | |a Suemizu, Hiroshi |e verfasserin |4 aut | |
| 700 | 1 | |a Fukasawa, Kazumasa |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Xenobiotica |d Abingdon : Taylor & Francis Group, 1971 |g 52(2022), 6, Seite 613-624 |h Online-Ressource |w (DE-627)KFL000005959 |w (DE-600)1485113-1 |w (DE-576)079719163 |x 1366-5928 |7 nnns |
| 773 | 1 | 8 | |g volume:52 |g year:2022 |g number:6 |g pages:613-624 |
| 856 | 4 | 0 | |u http://pharmazie.proxy.fid-lizenzen.de/fid/tandf-ejournals-pharmazie/doi.org/10.1080/00498254.2022.2127131 |m X:KFL |x Resolving-System |y FID Access |z lizenzpflichtig |
| 912 | |a ZDB-1-TFE | ||
| 912 | |a GBV_KFL | ||
| 912 | |a FID-PHARM | ||
| 935 | |i IMPORT_0628_prod_LgpH_05 | ||
| 951 | |a AR | ||
| 952 | |d 52 |j 2022 |e 6 |h 613-624 | ||