Tabata K

References (4)

Title : Application of a physiologically based pharmacokinetic model for the prediction of mirabegron plasma concentrations in a population with severe renal impairment - Konishi_2019_Biopharm.Drug.Dispos_40_176
Author(s) : Konishi K , Minematsu T , Nagasaka Y , Tabata K
Ref : Biopharmaceutics & Drug Disposition , 40 :176 , 2019
Abstract : We previously verified a physiologically based pharmacokinetic (PBPK) model for mirabegron in healthy subjects using the Simcyp Simulator by incorporating data on the inhibitory effect on cytochrome P450 (CYP) 2D6 and a multi-elimination pathway mediated by CYP3A4, uridine 5'-diphosphate-glucuronosyltransferase (UGT) 2B7 and butyrylcholinesterase (BChE). The aim of this study was to use this PBPK model to assess the magnitude of drug-drug interactions (DDIs) in an elderly population with severe renal impairment (sRI), which has not been evaluated in clinical trials. We first determined the system parameters, and meta-analyses of literature data suggested that the abundance of UGT2B7 and the BChE activity in an elderly population with sRI was almost equivalent to and 20% lower than that in healthy young subjects, respectively. Other parameters, such as the CYP3A4 abundance, for an sRI population were used according to those built into the Simcyp Simulator. Second, we confirmed that the PBPK model reproduced the plasma concentration-time profile for mirabegron in an sRI population (simulated area under the plasma concentration-time curve (AUC) was within 1.5-times that of the observed value). Finally, we applied the PBPK model to simulate DDIs in an sRI population. The PBPK model predicted that the AUC for mirabegron with itraconazole (a CYP3A4 inhibitor) was 4.12-times that in healthy elderly subjects administered mirabegron alone, and predicted that the proportional change in AUC for desipramine (a CYP2D6 substrate) with mirabegron was greater than that in healthy subjects. In conclusion, the PBPK model was verified for the purpose of DDI assessment in an elderly population with sRI.
ESTHER : Konishi_2019_Biopharm.Drug.Dispos_40_176
PubMedSearch : Konishi_2019_Biopharm.Drug.Dispos_40_176
PubMedID: 30985942

Title : Physiologically-based pharmacokinetic modeling for mirabegron: a multi-elimination pathway mediated by cytochrome P450 3A4, uridine 5'-diphosphate-glucuronosyltransferase 2B7, and butyrylcholinesterase - Konishi_2018_Xenobiotica__1
Author(s) : Konishi K , Minematsu T , Nagasaka Y , Tabata K
Ref : Xenobiotica , :1 , 2018
Abstract : 1. This was the first study to construct a physiologically-based pharmacokinetic (PBPK) model for mirabegron which incorporates the overall elimination pathways of metabolism by cytochrome P450 (CYP) 3A4, uridine 5'-diphosphate-glucuronosyltransferase (UGT) 2B7, and butyrylcholinesterase (BChE) and renal excretion. The objective was to assess the risk of drug-drug interactions (DDIs) by estimating the contribution of each elimination pathway and simulating the magnitude of the DDIs with UGT2B7 inhibitors. 2. A PBPK model for mirabegron was constructed to reproduce plasma concentration-time curves from a phase 1 study and the magnitude of the DDI with ketoconazole taking into account the overall elimination pathways. The PBPK model was subsequently verified using data from other DDI studies. 3. The constructed PBPK model estimated the contribution for each elimination pathway: 44% and 29% for CYP3A4 and UGT2B7 in the liver, 1.6% for UGT2B7 in the kidney, 3.2% for BChE in plasma, and 22% for renal excretion. 4. Co-administration of probenecid (an UGT2B7 inhibitor) or fluconazole (an UGT2B7 and CYP3A4 inhibitor) was predicted to increase area under the curve for mirabegron to 115% or 174%, respectively. 5. In conclusion, PBPK modeling and simulation revealed a low DDI risk for mirabegron following co-administration with BChE or UGT2B7 inhibitors.
ESTHER : Konishi_2018_Xenobiotica__1
PubMedSearch : Konishi_2018_Xenobiotica__1
PubMedID: 30301385

Title : Genetic Analysis and Characterization of Poly(aspartic acid) Hydrolase-1 from Sphingomonas sp. KT-1 - Hiraishi_2003_Biomacromolecules_4_80
Author(s) : Hiraishi T , Kajiyama M , Tabata K , Yamato I , Doi Y
Ref : Biomacromolecules , 4 :80 , 2003
Abstract : Sphingomonas sp. KT-1 hydrolyzes poly(aspartic acid) (PAA) containing alpha- and beta-amide units and has at least two different types of PAA hydrolases. The PAA hydrolase-1 hydrolyzes selectively beta-beta amide units in PAA. Molecular cloning of PAA hydrolase-1 from Sphingomonas sp. KT-1 has been carried out to characterize its gene products. Genetic analysis shows that the deduced amino acid sequence of PAA hydrolase-1 has a similarity with those of the catalytic domain of poly(3-hydroxybutyric acid) (PHB) depolymerases from Alcaligenes faecalis AE122 and Pseudomonas lemoignei. Site-specific mutation analysis indicates that (176)Ser is a part of a strictly conserved pentapeptide sequence (Gly-Xaa-Ser-Xaa-Gly), which is the lipase box, and plays as an active residue.
ESTHER : Hiraishi_2003_Biomacromolecules_4_80
PubMedSearch : Hiraishi_2003_Biomacromolecules_4_80
PubMedID: 12523851
Gene_locus related to this paper: 9sphn-q7wsc1

Title : Purification and characterization of poly(aspartic acid) hydrolase from Sphingomonas sp. KT-1 - Tabata_2001_Biomacromolecules_2_1155
Author(s) : Tabata K , Kajiyama M , Hiraishi T , Abe H , Yamato I , Doi Y
Ref : Biomacromolecules , 2 :1155 , 2001
Abstract : Poly(aspartic acid) (PAA) hydrolase was purified from Sphingomonas sp. KT-1 (JCM10459). The purified hydrolase degraded thermally synthesized PAA to oligomers. The molecular mass of PAA hydrolase was 30 kDa and the isoelectric point was 8.9. The optimum values of pH and temperature for PAA degradation were 10.0 and 40 degrees C, respectively. The investigation of the effect of inhibitors for the PAA-degrading activities has revealed that the PAA hydrolase is a serine-type hydrolase. The structural analysis of PAA-degraded products using (1)H and (13)C nuclear magnetic resonances has indicated that the purified enzyme hydrolyzes selectively the beta-amide linkage connecting with beta-aspartic acid units in PAA.
ESTHER : Tabata_2001_Biomacromolecules_2_1155
PubMedSearch : Tabata_2001_Biomacromolecules_2_1155
PubMedID: 11777387