The Effect of Paracetamol and Codeine Analgesic Combination on Serum Alanine Aminotransferase and Aspartate Aminotransferase Levels in Male Wistar Rats


  • Satrio Adi Wicaksono Department of Anesthesiology and Intensive Care, Faculty of Medicine, Diponegoro University, Semarang, Indonesia
  • Andi Muhammad Fatwa Mardin Department of Medicine, Faculty of Medicine, Diponegoro University, Semarang, Indonesia
  • Sulistiyati Bayu Utami Department of Cardiology and Vascular Medicine, Faculty of Medicine, Diponegoro University, Semarang, Indonesia



Analgesic, Paracetamol, Codeine, Alanine aminotransferase, Aspartate aminotransferase


BACKGROUND: Paracetamol and codeine are classified as different analgesic categories with different mechanism. The combination of both paracetamol and codeine as an analgesic works synergistically and may give better outcome in pain management in moderate-to-severe degree. However, the combination of those analgesics might bring side effects in liver.

AIM: This study was to determine the effect of analgesic combination of paracetamol and codeine on alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels of Wistar rats.

METHODS: This study was an experimental study with a pre- and post-test control group design. The study objects were 20 male Wistar rats with certain criteria, which were randomly divided into four groups, that is, control group (C), group with paracetamol therapy alone (32 mg/kgBW), group with codeine therapy alone (1.9 mg/kgBW), and group with combination therapy of paracetamol (32 mg/kgBW) and codeine (1.9 mg/kgBW). Analgesic drugs were administered orally 4 times a day for 28 days with gastric sonde. On the 29th day, blood samples were collected through retro-orbital blood vessels for measuring ALT and AST levels. Statistical tests used were one-way ANOVA and Kruskal–Wallis test.

RESULTS: They showed that there were no differences in ALT levels between C, P1, P2, and P3 in both at baseline and post-treatment. However, there were significant increases in ALT levels after treatment in comparison to baseline in the control group (C) (87.2 ± 18.43 vs. 40.6 ± 5.02; p < 0.05), P1 (78.9 ± 8.52 vs. 44.4 ± 1.14; p < 0.05), and P3 (86.4 ± 17.22 vs. 44.0 ± 1.00; p < 0.05). There were no differences in AST levels between C, P1, P2, and P3 at baseline, but there were significantly higher AST levels in P1, P2, and P3 in comparison to control at post-treatment (p < 0.05). There were no differences in AST levels between P1, P2, and P3 at post-treatment (p > 0.05). There were also significant increases in AST levels after treatment in comparison to baseline in the control group (C) (93.9 ± 1.10 vs. 37.7 ± 1.69; p < 0.05), P1 (97.6 ± 1.85 vs. 36.3 ± 1.22; p < 0.05), P2 (97.6 ± 1.70 vs. 37.7 ± 1.73; p < 0.05), and P3 (98.6 ± 0.79 vs. 36.4 ± 1.20; p < 0.05).

CONCLUSION: The combination therapy of paracetamol and codeine might not bring difference in serum ALT and AST levels compared to paracetamol therapy alone or codeine therapy alone.


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How to Cite

Wicaksono SA, Mardin AMF, Utami SB. The Effect of Paracetamol and Codeine Analgesic Combination on Serum Alanine Aminotransferase and Aspartate Aminotransferase Levels in Male Wistar Rats. Open Access Maced J Med Sci [Internet]. 2022 Sep. 30 [cited 2023 Mar. 21];10(B):2267-72. Available from: