更新于：2024-11-01

P-gp x HLA class I抗原

更新于：2024-11-01

基本信息

关联

项与 P-gp x HLA class I抗原相关的药物

C3B3-DB

靶点

HLA class I抗原 x P-gp

作用机制

HLA class I抗原调节剂 [+1]

在研机构-

原研机构

Chugai Pharmaceutical Co., Ltd.

在研适应症-

非在研适应症

血液肿瘤

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 P-gp x HLA class I抗原相关的临床结果

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100 项与 P-gp x HLA class I抗原相关的转化医学

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0 项与 P-gp x HLA class I抗原相关的专利（医药）

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项与 P-gp x HLA class I抗原相关的文献（医药）

2024-05-01·Clinical Pharmacology & Therapeutics

Model‐Based Prediction of Irinotecan‐Induced Grade 4 Neutropenia in Cancer Patients: Influence of Incorporating Germline Genetic Factors in the Model

Article

作者: Bies, Robert R ; Innocenti, Federico ; Forrest, Alan ; Wiltshire, Tim ; van Schaik, Ron H N ; Karas, Spinel ; Mathijssen, Ron H J

Neutropenia is the major dose‐limiting toxicity of irinotecan‐based therapy. The objective of this study was to assess whether inclusion of germline genetic variants into a population pharmacokinetic/pharmacodynamic model can improve prediction of irinotecan‐induced grade 4 neutropenia and identify novel variants of clinical value. A semimechanistic population pharmacokinetic/pharmacodynamic model was used to predict neutrophil response over time in 197 patients receiving irinotecan. Covariate analysis was performed for demographic/clinical factors and 4,781 genetic variants in 84 drug response‐ and toxicity‐related genes to identify covariates associated with neutrophil response. We evaluated the predictive value of the model for grade 4 neutropenia reflecting different clinical scenarios of available data on identified demographic/clinical covariates, baseline and post‐treatment absolute neutrophil counts (ANCs), individual pharmacokinetics, and germline genetic variation. Adding 8 genetic identified covariates (rs10929302 (UGT1A1), rs1042482 (DPYD), rs2859101 (HLA‐DQB3), rs61754806 (NR3C1), rs9266271 (HLA‐B), rs7294 (VKORC1), rs1051713 (ALOX5), and ABCB1 rare variant burden) to a model using only baseline ANCs improved prediction of irinotecan‐induced grade 4 neutropenia from area under the receiver operating characteristic curve (AUC‐ROC) of 50–64% (95% confidence interval (CI), 54–74%). Individual pharmacokinetics further improved the prediction to 74% (95% CI, 64–84%). When weekly ANC was available, the identified covariates and individual pharmacokinetics yielded no additional contribution to the prediction. The model including only ANCs at baseline and at week 1 achieved an AUC‐ROC of 78% (95% CI, 69–88%). Germline DNA genetic variants may contribute to the prediction of irinotecan‐induced grade 4 neutropenia when incorporated into a population pharmacokinetic/pharmacodynamic model. This approach is generalizable to drugs that induce neutropenia and ultimately allows for personalized intervention to enhance patient safety.

2023-04-01·Pharmacogenomics

Pharmacogenomics of Oxcarbazepine in the Treatment of Epilepsy

Review

作者: Yan, Xinjing ; Yuan, Yangyang ; Zhang, Linlin ; Zhang, Shuang ; Yuan, Yujie ; Ran, Yun Wei

Oxcarbazepine (OXC) is one of the preferred drugs for partial seizures and generalized tonic-clonic seizures. However, clinical studies have found that there are considerable differences among different populations in OXC therapeutic efficacy or safety that result from the function changes of metabolic enzymes, transporters and other receptors involved in pharmacokinetics and pharmacodynamics in vivo. The authors collected all the information on the clinically reported associations between variants of common genes (e.g., UGT1A9, HLA-B, ABCB1) and OXC. In conclusion, these associations based on variants are beneficial for adjusting the medication regimen, which could be useful for individualized treatment with OXC.

2023-01-02·Expert Opinion on Drug Metabolism & Toxicology

Pharmacogenomics in Asians: Differences and similarities with other human populations

Review

作者: Jinda, Pimonpan ; Sukasem, Chonlaphat ; Biswas, Mohitosh

INTRODUCTIONVarious pharmacogenomic (PGx) variants differ widely in different ethnicities. and clinical outcomes associated with these variants may also be substantially varied. Literature was searched in different databases, i.e. PubMed, ScienceDirect, Web of Science, and PharmGKB, from inception to 30 June 2022 for this review.AREAS COVEREDCertain PGx variants were distinctly varied in Asian populations compared to the other human populations, e.g. CYP2C19*2,*3,*17; CYP2C9*2,*3; CYP2D6*4,*5,*10,*41; UGT1A1*6,*28; HLA-B*15:02, HLA-B*15:21, HLA-B*58:01, and HLA-A*31:01. However, certain other variants do not vary greatly between Asian and other ethnicities, e.g. CYP3A5*3; ABCB1, and SLCO1B1*5. As evident in this review, the risk of major adverse cardiovascular events (MACE) was much stronger in Asian patients taking clopidogrel and who inherited the CYP2C19 loss-of-function alleles, e.g. CYP2C19*2 and*3, when compared to the western/Caucasian patients. Additionally, the risk of carbamazepine-induced severe cutaneous adverse drug reactions (SCARs) for the patients inheriting HLA-B*15:02 and HLA-B*15:21 alleles varied significantly between Asian and other ethnicities. In contrast, both Caucasian and Asian patients inheriting the SLCO1B1*5 variant possessed a similar magnitude of muscle toxicity, i.e. myopathy.EXPERT OPINIONAsian countries should take measures toward expanding PGx research, as well as initiatives for the purposes of obtaining clinical benefits from this newly evolving and economically viable treatment model.