Moderation of buprenorphine therapy for cocaine dependence efficacy by variation of the Prodynorphin gene.
Eur J Clin Pharmacol
; 78(6): 965-973, 2022 Jun.
Article
em En
| MEDLINE
| ID: mdl-35218405
ABSTRACT
PURPOSE:
The aim of this secondary analysis was to identify prodynorphin (PDYN) genetic markers moderating the therapeutic response to treatment of cocaine dependence with buprenorphine/naloxone (Suboxone®; BUP).METHODS:
Cocaine-dependent participants (N = 302) were randomly assigned to a platform of injectable, extended-release naltrexone (XR-NTX) and one of three daily medication arms 4 mg BUP (BUP4), 16 mg BUP (BUP16), or placebo (PLB) for 8 weeks (Parent Trial Registration Protocol ID NIDA-CTN-0048, Clinical Trials.gov ID NCT01402492). DNA was obtained from 277 participants. Treatment response was determined from weeks 3 to 7 over each 1-week period by the number of cocaine-positive urines per total possible urines.RESULTS:
In the cross-ancestry group, the PLB group had more cocaine-positive urines than the BUP16 group (P = 0.0021). The interactions of genetic variant × treatment were observed in the rs1022563 A-allele carrier group where the BUP16 group (N = 35) had fewer cocaine-positive urines (P = 0.0006) than did the PLB group (N = 26) and in the rs1997794 A-allele carrier group where the BUP16 group (N = 49) had fewer cocaine-positive urines (P = 0.0003) than did the PLB group (N = 58). No difference was observed in the rs1022563 GG or rs1997794 GG genotype groups between the BUP16 and PLB groups. In the African American-ancestry subgroup, only the rs1022563 A-allele carrier group was associated with treatment response.CONCLUSION:
These results suggest that PDYN variants may identify patients who are best suited to treatment with XR-NTX plus buprenorphine for cocaine use disorder pharmacotherapy.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Buprenorfina
/
Cocaína
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Transtornos Relacionados ao Uso de Cocaína
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Transtornos Relacionados ao Uso de Opioides
Tipo de estudo:
Clinical_trials
/
Guideline
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article