Disease Information

General Information of the Disease (ID: DIS00110)

• Name: Agranulocytosis
• ICD: ICD-11: 4B00

Type(s) of Resistant Mechanism of This Disease

  IDUE: Irregularity in Drug Uptake and Drug Efflux

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Clozapine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [1]

• Resistant Disease: Agranulocytosis [ICD-11: 4B00.0]
• Molecule Alteration: Missense mutation; 3435CC genotype
• Resistant Drug: Clozapine
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: PCR
• Mechanism Description: It was shown that 3435CC genotype carriers require greater doses of clozapine to achieve same plasma concentrations compared with 3435CT and 3435TT carriers. Similarly, a study carried out in Switzerland reported that 3435TT carriers had higher clozapine plasma concentrations.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [1]

• Sensitive Disease: Agranulocytosis [ICD-11: 4B00.0]
• Molecule Alteration: Missense mutation; 3435TT genotype
• Sensitive Drug: Clozapine
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: PCR
• Mechanism Description: It was shown that 3435CC genotype carriers require greater doses of clozapine to achieve same plasma concentrations compared with 3435CT and 3435TT carriers. Similarly, a study carried out in Switzerland reported that 3435TT carriers had higher clozapine plasma concentrations.

References

• Ref 1: Relation of the Allelic Variants of Multidrug Resistance Gene to Agranulocytosis Associated With Clozapine. J Clin Psychopharmacol. 2016 Jun;36(3):257-61. doi: 10.1097/JCP.0000000000000495.