RiteeshGrandhi/sciclaimeval-shared-task huggingface dataset:
Conclusion
Crizotinib has a potent inhibitory effect on the metabolism of tramadol. Although short-term administration of crizotinib does not lead to toxicity in metabolic organs, the serum levels of ALT and AST increase significantly, accompanied by a reduction in CYP abundance. This collective data could aid in the precise administration of tramadol and crizotinib as personalized medicine.
Figure 1: Determine the interaction between representative tyrocine kinase inhibitors and tramadol.
(A) The inhibitory effect of 23 types of tyrosine kinase inhibitors on the production of O-desmethyl tramadol in RLM compared with the control group. (B) Evaluate the half-maximal inhibitory concentration (IC50) of crizotinib with various concentrations (0.01, 0.1, 1, 10, 25, 50 and 100 µM) on tramadol metabolism in RLM and HLM. Data are presented as the mean ± SD, n = 3.

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DOI: 10.7717/peerj.17446/fig-1
Figure 2: Primary lineweaver-Burk plot and secondary plot for Ki and αKi in the inhibition of tramadol metabolism by crizotinib with various concentrations in (A) RLM and (B) HLM, respectively.
Data are presented as the mean ± SD, n = 3.

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DOI: 10.7717/peerj.17446/fig-2
Figure 3: Mean concentration–time curve of tramadol and O-desmethyl tramadol in four groups.
(A) Evaluate the effect of a single dose (45 mg/kg) of crizotinib. (B) Evaluate the effect of multiple doses (45 mg/kg) of crizotinib for 7 days. Data are presented as the mean ± SD, n = 5.

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DOI: 10.7717/peerj.17446/fig-3
Figure 4: The effect of crizotinib on tissue morphology and liver function.
(A) The results of H&E staining of tissue sections for liver (a), kidney (b) and small intestine (c) in three groups. (B) The value of serum ALT (U/L) and AST (U/L) in three groups. Data are presented as the mean ± SD, n = 3; Vs Control, * P < 0.05, ** P < 0.01.

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DOI: 10.7717/peerj.17446/fig-4
Figure 5: Crizotinib suppressing the activities of CYP by reducing the abundance of CYP enzymes.
(A) The effect of crizotinib on the function of CYP2D1 (dextromethorphan as probe substrate) and CYP3A2 (midazolam as probe substrate) in the liver of three groups. (B) The chromatogram and (C) the total amount of CYP in rat liver microsomes quantified by CO quantitative method in three groups. Data are presented as the mean ± SD, n = 3; Vs Control, *** P < 0.001.

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DOI: 10.7717/peerj.17446/fig-5
The main pharmacokinetic parameters of tramadol and O-desmethyl tramadol in group A and group B.
The main pharmacokinetic parameters of tramadol and O-desmethyl tramadol in group C and group D.