Back to Search
Start Over
Antituberculosis Drug-Induced Adverse Events in the Liver, Kidneys, and Blood: Clinical Profiles and Pharmacogenetic Predictors.
- Source :
-
Clinical pharmacology and therapeutics [Clin Pharmacol Ther] 2018 Aug; Vol. 104 (2), pp. 326-334. Date of Electronic Publication: 2017 Nov 23. - Publication Year :
- 2018
-
Abstract
- Antituberculosis drug-induced adverse drug reactions (ATD-ADRs) are increasing globally, and it is key to identify candidate ATD-ADRs loci for clinical management. We prospectively enrolled 1,235 highly suspicious tuberculosis (TB) inpatients to investigate the profiles and genetic risk factors of ATD-ADRs in the liver, kidneys, and blood. Overall, 644 subjects were eligible and genotyped for seven polymorphisms in drug-metabolizing enzymes and transporter genes. Clinical follow-up and blood analysis were performed regularly. We found that a notable rate of ATD-ADRs (incidence: 16.5%, drug intervention rate: 10.4%), mainly involving hepatotoxicity (10.6%) and leukopenia (3.3%) in western China. CYP2D6 rs1135840 and NUDT15 rs116855232 increased the risks of hepatotoxicity and leukopenia with an odds ratio of 2.52 and 4.97, respectively. Both variants showed excellent negative predictive values (93.7% and 98.1%, respectively) but moderate sensitivities (72.7% and 52.4%, respectively). These data provide new insight into ATD-ADRs in the Chinese population and may offer future leads for diagnosis and treatment.<br /> (© 2017 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.)
- Subjects :
- Adult
Chemical and Drug Induced Liver Injury diagnosis
Chemical and Drug Induced Liver Injury epidemiology
China
Female
Humans
Incidence
Kidney Diseases diagnosis
Kidney Diseases epidemiology
Leukopenia diagnosis
Leukopenia epidemiology
Male
Middle Aged
Prospective Studies
Risk Assessment
Risk Factors
Young Adult
Antitubercular Agents adverse effects
Chemical and Drug Induced Liver Injury genetics
Cytochrome P-450 CYP2D6 genetics
Kidney Diseases chemically induced
Kidney Diseases genetics
Leukopenia chemically induced
Leukopenia genetics
Pharmacogenomic Variants
Polymorphism, Single Nucleotide
Pyrophosphatases genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1532-6535
- Volume :
- 104
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Clinical pharmacology and therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 29071720
- Full Text :
- https://doi.org/10.1002/cpt.924