Effect of Hemodialysis on Efficacy and Pharmacokinetics of Sofosbuvir Coformulated with Either Daclatasvir or Ledipasvir in Patients with End-Stage Renal Disease.
Adult
Aged
Benzimidazoles
/ pharmacokinetics
Carbamates
/ pharmacokinetics
Clinical Trials as Topic
Drug Monitoring
Drug Therapy, Combination
Female
Fluorenes
/ pharmacokinetics
Hepatitis C, Chronic
/ complications
Humans
Imidazoles
/ pharmacokinetics
Kidney Failure, Chronic
/ complications
Male
Middle Aged
Pyrrolidines
/ pharmacokinetics
Renal Dialysis
/ adverse effects
Sofosbuvir
/ pharmacokinetics
Treatment Outcome
Valine
/ analogs & derivatives
Direct-acting antivirals
Hemodialysis
Hepatitis C
Pharmacokinetic
Removal
Journal
Blood purification
ISSN: 1421-9735
Titre abrégé: Blood Purif
Pays: Switzerland
ID NLM: 8402040
Informations de publication
Date de publication:
2020
2020
Historique:
received:
21
11
2018
accepted:
25
02
2019
pubmed:
15
4
2020
medline:
5
6
2021
entrez:
15
4
2020
Statut:
ppublish
Résumé
Direct-acting antivirals (DAAs) play a key role in the eradication of hepatitis C virus (HCV) infection. However, limited data are available on DAA for treating HCV infection in hemodialysis (HD) patients. This study was to evaluate the pharmacokinetic characteristics and effectiveness of daclatasvir/sofosbuvir (DAC/SOF) and ledipasvir/SOF (LDV/SOF) in HD patients. Seven patients were given SOF coadministered with DAC or LDV once daily for 12 weeks. The plasma concentrations of SOF007, DAC, and LDV were determined by high-performance liquid chromatography-electrospray ionization tandem mass spectrometry. A sustained virologic response in week 12 (SVR12) was achieved in 6 (100%) patients, except for 1 patient dying due to severe cerebral hemorrhage not related to antiviral therapy. The extraction ratio of SOF007 was 66.67%, and the estimated HD clearance of SOF007 was 5.65 L/h. The combination of SOF with either DAC or LDV is well tolerated and offers high SVR12 in HD patients.
Sections du résumé
BACKGROUND/AIMS
Direct-acting antivirals (DAAs) play a key role in the eradication of hepatitis C virus (HCV) infection. However, limited data are available on DAA for treating HCV infection in hemodialysis (HD) patients. This study was to evaluate the pharmacokinetic characteristics and effectiveness of daclatasvir/sofosbuvir (DAC/SOF) and ledipasvir/SOF (LDV/SOF) in HD patients.
METHODS
Seven patients were given SOF coadministered with DAC or LDV once daily for 12 weeks. The plasma concentrations of SOF007, DAC, and LDV were determined by high-performance liquid chromatography-electrospray ionization tandem mass spectrometry.
RESULTS
A sustained virologic response in week 12 (SVR12) was achieved in 6 (100%) patients, except for 1 patient dying due to severe cerebral hemorrhage not related to antiviral therapy. The extraction ratio of SOF007 was 66.67%, and the estimated HD clearance of SOF007 was 5.65 L/h.
CONCLUSION
The combination of SOF with either DAC or LDV is well tolerated and offers high SVR12 in HD patients.
Identifiants
pubmed: 32289799
pii: 000499161
doi: 10.1159/000499161
doi:
Substances chimiques
Benzimidazoles
0
Carbamates
0
Fluorenes
0
Imidazoles
0
Pyrrolidines
0
ledipasvir
013TE6E4WV
Valine
HG18B9YRS7
daclatasvir
LI2427F9CI
Sofosbuvir
WJ6CA3ZU8B
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
692-699Informations de copyright
© 2020 S. Karger AG, Basel.