title: 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.
authors.affiliation: Department of Hospital Pharmacy, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Ishida
authors.affiliation: Department of Hospital Pharmacy, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan. Electronic address: naitou@hama-med.ac.jp.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Naito
authors.affiliation: Department of Hospital Pharmacy, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: Hikaru
authors.initials: H
authors.lastname: Sato
authors.affiliation: Department of Hospital Pharmacy, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Kawakami
mesh_terms: D000368:Aged; D000701:Analgesics, Opioid / Q000097:blood* / Q000627:therapeutic use; D000072716:Cancer Pain / Q000097:blood* / Q000188:drug therapy; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D005260:Female; D005283:Fentanyl / Q000097:blood* / Q000627:therapeutic use; D005838:Genotype; D006801:Humans; D006888:Hydroxycholesterols / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012727:Sex Characteristics
chemical_list: D000701:Analgesics, Opioid; D006888:Hydroxycholesterols; C099828:cholest-5-ene-3,4-diol; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D005283:Fentanyl
keywords: 4β-Hydroxycholesterol; CYP3A5; Cancer pain; Fentanyl; Gender; Pharmacokinetics; Transdermal system