Pharmacokinetic assessment of rifampicin and des-acetyl rifampicin in carbon tetrachloride induced liver injury model in Wistar rats.
J Complement Integr Med
; 21(1): 38-45, 2024 Mar 01.
Article
in En
| MEDLINE
| ID: mdl-38140744
ABSTRACT
OBJECTIVES:
Preclinical evidence is needed to assess drug-metabolite behaviour in compromised liver function for developing the best antitubercular treatment (ATT) re-introduction regimen in drug-induced liver injury (DILI). The pharmacokinetic behavior of rifampicin (RMP) and its active metabolite des-acetyl-rifampicin (DARP) in DILI's presence is unknown. To study the pharmacokinetic behavior of RMP and DARP in the presence of carbon tetrachloride (CCl4) plus ATT-DILI in rats.METHODS:
Thirty rats used in the experiment were divided equally into six groups. We administered a single 0.5â¯mL/kg CCl4 intraperitoneal injection in all rats. Groups II, III, IV, and V were started on daily oral RMP alone, RMP plus isoniazid (INH), RMP plus pyrazinamide (PZA), and the three drugs INH, RMP, and PZA together, respectively, for 21-days subsequently. Pharmacokinetic (PK) sampling was performed at 0, 0.5, 1, 3, 6, 12, and 24â¯h post-dosing on day 20. We monitored LFT at baseline on days-1, 7, and 21 and sacrificed the rats on the last day of the experiment.RESULTS:
ATT treatment sustained the CCl4-induced liver injury changes. A significant rise in mean total bilirubin levels was observed in groups administered rifampicin. The triple drug combination group demonstrated 1.43- and 1.84-times higher area-under-the-curve values of RMP (234.56±30.66 vs. 163.55±36.14⯵gâ¯h/mL) and DARP (16.15±4.50 vs. 8.75±2.79⯵gâ¯h/mL) compared to RMP alone group. Histological and oxidative stress changes supported underlying liver injury and PK alterations.CONCLUSIONS:
RMP metabolism inhibition by PZA, more than isoniazid, was well preserved in the presence of underlying liver injury.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Chemical and Drug Induced Liver Injury
/
Chemical and Drug Induced Liver Injury, Chronic
Limits:
Animals
Language:
En
Journal:
J Complement Integr Med
Year:
2024
Document type:
Article
Affiliation country:
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