Sex Differences in the Blood Concentration of Tacrolimus in Systemic Lupus Erythematosus and Rheumatoid Arthritis Patients with CYP3A5*3/*3.
The purpose of this study was to describe the impact of sex and cytochrome P450 3A5 (CYP3A5) variant on the blood concentration of tacrolimus in patients with systemic lupus erythematosus or rheumatoid arthritis. The blood concentration of tacrolimus (ng/mL) divided by the daily dose of tacrolimus (mg/day) and the patient's weight (kg) (C/D) was obtained from 55 patients. The C/D value was analysed according to genetic variation in CYP3A5 or ATP binding cassette subfamily B member 1 (ABCB1), sex, and age. The C/D value in the CYP3A5*3/*3 group was significantly higher than in the CYP3A5*1/*1 and *1/*3 groups (p < 0.05, effect size: d = 1.40). In the CYP3A5*3/*3 group, the concentration of tacrolimus was significantly higher in men than in women (p < 0.05, effect size: d = 1.78). Furthermore, in the CYP3A5*3/*3 group, the concentration of tacrolimus was significantly higher in women aged over 50 years than in women aged under 50 years (p < 0.05, effect size: d = 1.18). In contrast, ABCB1 genetic variations did not show any significant effect on the C/D value. Since the blood concentration of tacrolimus in patients with CYP3A5*3/*3 varies depending on sex and age, these factors should be considered when studying the difference of sex in CYP3A.
Department of Pharmacy, Gunma University Hospital, 3-39-15 Showa-machi, Maebashi, Gunma, 371-8511, Japan.|Department of Pharmacy, NTT Medical Center Tokyo, 5-9-22 Higashi-Gotanda, Shinagawa-ku, Tokyo, 141-8625, Japan.
Ayano
A
Ito
Faculty of Pharmacy, Takasaki University of Health and Welfare, 60 Ohrui-machi, Takasaki, Gunma, 370-0033, Japan.
Yuko
Y
Okada
Department of Pharmacy, Gunma University Hospital, 3-39-15 Showa-machi, Maebashi, Gunma, 371-8511, Japan. thashita@phar.nagoya-cu.ac.jp.|Department of Clinical Pharmacology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan. thashita@phar.nagoya-cu.ac.jp.|Center for Medical Education, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan. thashita@phar.nagoya-cu.ac.jp.|Department of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, 467-8603, Japan. thashita@phar.nagoya-cu.ac.jp.
Tadahiro
http://orcid.org/0000-0001-7521-145X
T
Hashita
Department of Pharmacy, Gunma University Hospital, 3-39-15 Showa-machi, Maebashi, Gunma, 371-8511, Japan.|Department of Clinical Pharmacology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan.|Center for Medical Education, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan.|Center for Social Pharmacy and Pharmaceutical Care Sciences, Division of Pharmaceutical Care Sciences, Keio University Faculty of Pharmacy, 1-5-30 Shibakoen, Minato-ku, Tokyo, 105-8512, Japan.
Tohru
T
Aomori
Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan.
Keiju
K
Hiromura
Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan.
Yoshihisa
Y
Nojima
Department of Pharmacy, Gunma University Hospital, 3-39-15 Showa-machi, Maebashi, Gunma, 371-8511, Japan.|Department of Clinical Pharmacology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan.|Center for Social Pharmacy and Pharmaceutical Care Sciences, Division of Pharmaceutical Care Sciences, Keio University Faculty of Pharmacy, 1-5-30 Shibakoen, Minato-ku, Tokyo, 105-8512, Japan.
Tomonori
T
Nakamura
Department of Pharmacy, Gunma University Hospital, 3-39-15 Showa-machi, Maebashi, Gunma, 371-8511, Japan.|Department of Clinical Pharmacology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan.
Takuya
T
Araki
Department of Pharmacy, Gunma University Hospital, 3-39-15 Showa-machi, Maebashi, Gunma, 371-8511, Japan.|Department of Clinical Pharmacology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan.
Koujirou
K
Yamamoto
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism*; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood* / Q000493:pharmacokinetics / Q000494:pharmacology; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012737:Sex Factors; D016559:Tacrolimus / Q000097:blood* / Q000493:pharmacokinetics / Q000494:pharmacology; D014018:Tissue Distribution; D055815:Young Adult
D015415:Biomarkers; D007166:Immunosuppressive Agents; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus
ABCB1; CYP3A4; CYP3A5; Sex difference; Tacrolimus