Relationship between the plasma fentanyl and serum 4β-hydroxycholesterol based on CYP3A5 genotype and gender in patients with cancer pain

Abstract

This study aimed to evaluate the relationship between the concentrations of plasma fentanyl and serum 4β-hydroxycholesterol based on CYP3A5 genotype and gender in cancer patients. Thirty-three Japanese cancer patients treated with transdermal fentanyl were enrolled. The concentrations of plasma fentanyl and norfentanyl, and serum 4β-hydroxycholesterol and total cholesterol were determined at day 8 or later after starting the medication. The plasma fentanyl concentration was significantly higher in the CYP3A5*3/*3 group than in the *1 allele carrier group. The *3/*3 group had a lower metabolic ratio of fentanyl. The serum 4β-hydroxycholesterol concentration and its ratio to total cholesterol were significantly lower in the CYP3A5*3/*3 group than in the *1 allele carrier group. The concentrations of plasma fentanyl and serum 4β-hydroxycholesterol were significantly higher in women than in men. Gender did not affect the metabolic ratio of fentanyl or the concentration ratio of 4β-hydroxycholesterol. The plasma fentanyl concentration was not correlated with the serum 4β-hydroxycholesterol concentration, while the metabolic ratio of fentanyl was slightly correlated with the serum concentration ratio of 4β-hydroxycholesterol. In conclusion, CYP3A5*3 and gender affected the plasma fentanyl and serum 4β-hydroxycholesterol concentrations in cancer patients. However, the plasma disposition of fentanyl was not determined using the serum 4β-hydroxycholesterol concentration.

Impact of CYP3A5 genotype on tolvaptan pharmacokinetics and their relationships with endogenous markers of CYP3A activity and serum sodium level in heart failure patients

“…CYP3A5-deficient patients had close to double the plasma concentrations of some CYP3A5 substrates. 12,13 The CYP3A5 genotype had no relationship with the metabolic ratios of tolvaptan in the present study. These data indicate that CYP3A5 participates in both the production and elimination of the tolvaptan metabolites.…”

“…27 The CYP3A5*1 allele carriers had 1.5 times higher plasma 4β-OHC and 1.7 times higher plasma 4β-OHC/TC in cancer patients. 13 In the present study population, plasma 4β-OHC may not be useful for clear discrimination of the homozygous CYP3A5*3 allele. The plasma 25-OHD level was not different between the CYP3A5 genotypes.…”

“…11 The CYP3A5*3/*3 genotype, which is characterized as the almost complete absence of CYP3A5 protein, decreases drug clearances of CYP3A5 substrates such as tacrolimus and fentanyl in patients. 12,13 P-glycoprotein also has several SNPs affecting its transport activity. 14 The ABCB1 3435TT genotype elevates the plasma exposures of tacrolimus and digoxin through increased intestinal absorption in human beings.…”

“…17,18 Plasma 4β-OHC is also useful for the discrimination of patients with CYP3A5*3/*3. 13 Plasma 25-hydroxyvitamin D (25-OHD) is another promising biomarker of CYP3A activity. Vitamin D eventually contributes to the increase in mRNA expression and activity level of CYP3A, leading to high metabolism of CYP3A substrates.…”

Analyses of Respiratory Depression Associated with Opioids in Cancer Patients Based on the Japanese Adverse Drug Event Report Database

“…19,20) However, in a systematic review and meta-analysis, Gupta et al reported there was no significant association between postoperative opioid-induced respiratory depression and sex. 21) In the present study, the ROR trend for each opioid for sex varied. RORs of six opioids exceeded 1, suggesting respiratory depression related with these opioids may occur preferentially in males compared with females, while three opioids showed the opposite tendency.…”