Evidence of increased CPY3A4 activity in African Americans.

Abstract

Clinical Pharmacology & Therapeutics (1996) 59, 158–158; doi:

The pharmacokinetics and metabolic disposition of tacrolimus: A comparison across ethnic groups

“…11,13,26 However, the results of pharmacokinetic studies in which other CYP3A substrates were compared across different ethnic groups are inconsistent. 16,[19][20][21] Our study showed statistically significant differences between the absolute F and C max of tacrolimus in subjects from three different ethnic backgrounds. African American subjects had a significantly lower C max than either Latin American or white subjects, as well as a significantly lower F than the white subjects in our study.…”

“…Most studies that have reported ethnic differences in the pharmacokinetic disposition of the immunosuppressant cyclosporine have attributed these differences to a greater activity of CYP3A enzymes 11 , 13 , 26 . However, the results of pharmacokinetic studies in which other CYP3A substrates were compared across different ethnic groups are inconsistent 16 , 19 , 20 , 21…”

“…11 In several of these studies, African American patients specifically were characterized as patients with highly variable cyclosporine (INN, ciclosporin) pharmacokinetics and a correspondingly higher incidence of rejection than white patients with transplants. [12][13][14][15] Lang et al 16 suggested that African American people are characterized by more active CYP3A enzymes than white people, on the basis of triazolam pharmacokinetics. This may result in a lower and more variable oral bioavailability, as well as an increased clearance in African American patients in comparison with white patients.…”

A Comparison of the Pharmacokinetics and Pharmacodynamics of Docetaxel between African-American and Caucasian Cancer Patients: CALGB 9871

“…Ethnic differences in apparent oral drug clearance were also suggested by studies of age-and weight-matched African-American and Caucasian healthy volunteer subjects (n = 8, both groups) who received oral triazolam. The mean triazolam area under the plasma concentration versus time curve (AUC) was 4.5 times higher in Caucasian subjects compared with African-American subjects (15). The apparent oral clearance of methylprednisolone in African-American renal transplant patients was also reported to be significantly increased compared with that in Caucasian renal transplant patients (16).…”

The effect of aprepitant and race on the pharmacokinetics of cyclophosphamide in breast cancer patients

“…More DCE formation may be due to genetic polymorphisms as all studied African Americans carried variant alleles in at least two genotypes of CYP3A4, CYP3A5, and/or CYP2B6. Several other studies have observed that African Americans have altered PK of many CYP3A4/5 substrates including cyclosporine, triazolam, and methylprednisolone [25][26][27][28]. In patients receiving combination chemotherapy containing fluorouracil, epirubicin, and cyclophosphamide (FEC), slightly higher incidence of grade 2 or higher non-hematologic toxicity was seen in African Americans (75%) than in Caucasians (64%), although a slightly higher incidence of hematologic toxicity was seen in Caucasians (36%) than African Americans (25%) [29].…”