ArticleMedical science monitor : international medical journal of experimental and clinical research2015
Serum alanine transaminase total bilirubin concentrations predict CYP3A activity as measured by midazolam and 1'-hydroxylation.
Article in Medical science monitor : international medical journal of experimental and clinical research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed, 8 citations in OpenAlex.
- CYP3A4*1B and CYP3A5*3 SNPs significantly impact the response of Egyptian candidates to high-intensity statin therapy to atorvastatin.European journal of medical research · 2024Article
- Resistance to Neuromuscular Blockade by Rocuronium in Surgical Patients with Spastic Cerebral Palsy.Journal of personalized medicine · 2021Article
- Vitamin D3 Is Transformed into 1,25(OH)2D3 by Triggering CYP3A11(CYP3A4) Activity and Hydrolyzing Midazolam.Medical science monitor : international medical journal of experimental and clinical research · 2019Article
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3 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundMicrosomal enzyme P450 (CYP450) plays an important role in metabolism of most xenobiotics. The activity of CYP3A decreases in patients with liver dysfunction. However, whether serum concentrations of liver enzymes reflect the activity of CYP3A is unclear. We aimed to search for a new clue to predict the activity of CYP3A and guide clinical medication. MATERIAL AND
methodsForty-five patients undergoing surgery under general anesthesia were enrolled in the study, including 15 cases with normal liver function (Group N), 15 cases with moderate fatty liver according to both the results of ultrasonic diagnosis of moderate fatty liver and the laboratory results of elevated alanine transaminase less than 3 times the normal (Group M), and 15 cases with end-stage liver disease (Group S). Each patient received a single dose of 5 mg midazolam intravenously. CYP3A activity was measured by plasma 1'hydroxymidsazolam/midazolam (1'-OH-MDZ/MDZ) ratio at 2 h after administration of midazolam.
resultsThey was no significant difference in CYP3A activity between the patients with normal liver function and moderate fatty liver (P=0.332). The activity of CYP3A in Group S was lower than in Group N and Group M (P=0.000). Multiple linear regression analysis showed a statistically significant linear relationship between the activity of CYP3A and alanine transaminase (ALT, R2=0.682, P=0.000), and total bilirubin (TB, R2=0.519, P=0.002). There were no other factors, including albumin (ALB, P=0.881) and alkaline phosphatase (ALP, P=0.497), correlated with the activity of CYP3A.
conclusionsWe conclude that the activity of CYP3A in patients with end-stage liver disease decreased. The decrease in the activity of CYP3A was determined by the increase in the serum concentration of ALT and TB and not by patient's age or body weight. ALT and TB therefore might have predictive value for the activity of CYP3A. An abnormal liver function test likely gives the clinician a hint about dosage adjustment.
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