Pharmacokinetic assessment of pyrazinamide and pyrazinoic acid in carbon tetrachloride-induced liver injury model in Wistar Rats
Background: We investigated the pharmacokinetic behavior of pyrazinamide (PZA) and pyrazinoic acid (PA) in the presence of carbon-tetrachloride (CCl4) plus antitubercular treatment (ATT) drug-induced liver injury (DILI) in rats. Methods: Thirty rats utilized in the experiment were separated equally...
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2023-01-01
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| Series: | Journal of Pharmacy and Bioallied Sciences |
| Subjects: | |
| Online Access: | http://www.jpbsonline.org/article.asp?issn=0975-7406;year=2023;volume=15;issue=3;spage=146;epage=151;aulast=Sharma |
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| author | Swati Sharma Vishal Sharma Sunil Taneja Alka Bhatia Aishwarya Anand Dibyajyoti Banerjee Amol N Patil |
| author_facet | Swati Sharma Vishal Sharma Sunil Taneja Alka Bhatia Aishwarya Anand Dibyajyoti Banerjee Amol N Patil |
| author_sort | Swati Sharma |
| collection | DOAJ |
| description | Background: We investigated the pharmacokinetic behavior of pyrazinamide (PZA) and pyrazinoic acid (PA) in the presence of carbon-tetrachloride (CCl4) plus antitubercular treatment (ATT) drug-induced liver injury (DILI) in rats. Methods: Thirty rats utilized in the experiment were separated equally into five groups. Each rat was injected with 0.5 ml/kg CCl4 intra-peritoneal injection on day zero. Group, I rats did receive only CCl4 (single i.p. injection, 0.5 ml/Kg in olive oil in a 1:1 ratio). Groups II, III, IV, and V did receive daily oral PZA, PZA plus isoniazid (INH), rifampicin (RMP) plus pyrazinamide (PZA), and three drugs together, respectively, for 21-days. Pharmacokinetic sampling was performed at 0, 0.5,1,3,6,12 and 24 hours post-dosing on day-20. Liver function test (LFT) was assessed at days 0,1,7, and 21 days after CCl4 and ATT administration, and rats were sacrificed on the last experiment day. Results: ATT treatment maintained the liver function changes initiated by CCl4 administration. An evidential LFT rise was observed in groups administered with pyrazinamide. Co-administration of Isoniazid caused a 2.02 and 1.78 times increase in Area-under-the-curve (AUC) values of PZA and PA, respectively (p < 0.05). Histological and oxidative-stress changes supported the biochemical and pharmacokinetic observations. Conclusion: The enzyme inhibitory capacity of isoniazid is well-preservd in CCl4-induced liver injury. |
| first_indexed | 2024-03-11T14:48:19Z |
| format | Article |
| id | doaj.art-0ac424f20fc14b51920cd638d3829199 |
| institution | Directory Open Access Journal |
| issn | 0975-7406 |
| language | English |
| last_indexed | 2024-03-11T14:48:19Z |
| publishDate | 2023-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Journal of Pharmacy and Bioallied Sciences |
| spelling | doaj.art-0ac424f20fc14b51920cd638d38291992023-10-30T10:31:30ZengWolters Kluwer Medknow PublicationsJournal of Pharmacy and Bioallied Sciences0975-74062023-01-0115314615110.4103/jpbs.jpbs_333_23Pharmacokinetic assessment of pyrazinamide and pyrazinoic acid in carbon tetrachloride-induced liver injury model in Wistar RatsSwati SharmaVishal SharmaSunil TanejaAlka BhatiaAishwarya AnandDibyajyoti BanerjeeAmol N PatilBackground: We investigated the pharmacokinetic behavior of pyrazinamide (PZA) and pyrazinoic acid (PA) in the presence of carbon-tetrachloride (CCl4) plus antitubercular treatment (ATT) drug-induced liver injury (DILI) in rats. Methods: Thirty rats utilized in the experiment were separated equally into five groups. Each rat was injected with 0.5 ml/kg CCl4 intra-peritoneal injection on day zero. Group, I rats did receive only CCl4 (single i.p. injection, 0.5 ml/Kg in olive oil in a 1:1 ratio). Groups II, III, IV, and V did receive daily oral PZA, PZA plus isoniazid (INH), rifampicin (RMP) plus pyrazinamide (PZA), and three drugs together, respectively, for 21-days. Pharmacokinetic sampling was performed at 0, 0.5,1,3,6,12 and 24 hours post-dosing on day-20. Liver function test (LFT) was assessed at days 0,1,7, and 21 days after CCl4 and ATT administration, and rats were sacrificed on the last experiment day. Results: ATT treatment maintained the liver function changes initiated by CCl4 administration. An evidential LFT rise was observed in groups administered with pyrazinamide. Co-administration of Isoniazid caused a 2.02 and 1.78 times increase in Area-under-the-curve (AUC) values of PZA and PA, respectively (p < 0.05). Histological and oxidative-stress changes supported the biochemical and pharmacokinetic observations. Conclusion: The enzyme inhibitory capacity of isoniazid is well-preservd in CCl4-induced liver injury.http://www.jpbsonline.org/article.asp?issn=0975-7406;year=2023;volume=15;issue=3;spage=146;epage=151;aulast=Sharmacarbon tetrachlorideliver injurypharmacokineticspharmacometabolomicspharmacometabonomicspyrazinamidepyrazines acidtherapeutic drug monitoring |
| spellingShingle | Swati Sharma Vishal Sharma Sunil Taneja Alka Bhatia Aishwarya Anand Dibyajyoti Banerjee Amol N Patil Pharmacokinetic assessment of pyrazinamide and pyrazinoic acid in carbon tetrachloride-induced liver injury model in Wistar Rats Journal of Pharmacy and Bioallied Sciences carbon tetrachloride liver injury pharmacokinetics pharmacometabolomics pharmacometabonomics pyrazinamide pyrazines acid therapeutic drug monitoring |
| title | Pharmacokinetic assessment of pyrazinamide and pyrazinoic acid in carbon tetrachloride-induced liver injury model in Wistar Rats |
| title_full | Pharmacokinetic assessment of pyrazinamide and pyrazinoic acid in carbon tetrachloride-induced liver injury model in Wistar Rats |
| title_fullStr | Pharmacokinetic assessment of pyrazinamide and pyrazinoic acid in carbon tetrachloride-induced liver injury model in Wistar Rats |
| title_full_unstemmed | Pharmacokinetic assessment of pyrazinamide and pyrazinoic acid in carbon tetrachloride-induced liver injury model in Wistar Rats |
| title_short | Pharmacokinetic assessment of pyrazinamide and pyrazinoic acid in carbon tetrachloride-induced liver injury model in Wistar Rats |
| title_sort | pharmacokinetic assessment of pyrazinamide and pyrazinoic acid in carbon tetrachloride induced liver injury model in wistar rats |
| topic | carbon tetrachloride liver injury pharmacokinetics pharmacometabolomics pharmacometabonomics pyrazinamide pyrazines acid therapeutic drug monitoring |
| url | http://www.jpbsonline.org/article.asp?issn=0975-7406;year=2023;volume=15;issue=3;spage=146;epage=151;aulast=Sharma |
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