title: African American renal transplant recipients (RTR) require higher tacrolimus doses to achieve target levels compared to white RTR: does clotrimazole help?
abstract: The number of African Americans (AAs) on the kidney waiting list is increasing in the United States. Several studies showed that AAs are at higher risk for rejection and graft loss. Because of genetic polymorphisms, AAs may metabolize calcineurin inhibitors faster than Caucasian (C) individuals. The goal of this study is to evaluate the tacrolimus (TAC) dose required to reach therapeutic levels and to assess the impact of clotrimazole on TAC metabolism in AAs compared to C patients. One hundred forty-two AA renal transplant recipients (RTRs) were compared to 309 C RTRs. Demographics were similar in both groups. Induction therapy and maintenance immunosuppression were similar in both groups and included TAC, mycophenolate acid (MPA), and steroids. The goal in all RTRs was to maintain a 12-hour trough level of 10 to 15 ng/mL in the first 3 months, 8 to 10 ng/mL for the first year, and 5 to 8 ng/mL thereafter. To achieve these levels, AA RTRs require a significantly higher dosage of TAC compared to C patients (5.9 ± 2.9 vs 3.6 ± 2 mg/d, respectively, P < .0001). By multivariate analysis, TAC dose requirements were not affected by age, gender, MPA or prednisone dose, diabetes, and renal function. Adding clotrimazole (CTM) to the RTR regimen significantly reduced the TAC dose requirements in all RTRs. When CTM was used, the TAC dose requirement was not statistically significantly different between AA and C patients (2.6 ± 1.2 mg/d vs 1.8 ± 1.5 mg/d, P = .07). We conclude that AAs required a higher TAC dose to reach the desired trough level in RTRs compared to C RTRs. The use of CTM eliminates the need for higher doses of TAC in AA RTRs. Thus, CTM may aid AA RTRs in achieving therapeutic TAC levels while reducing drug costs.
authors: Department of Surgery, The State University of New York at Buffalo, Buffalo, New York. Electronic address: mlaftavi@buffalo.edu.
authors: M R
authors: MR
authors: Laftavi
authors: O
authors: O
authors: Pankewycz
authors: S
authors: S
authors: Patel
authors: N
authors: N
authors: Nader
authors: R
authors: R
authors: Kohli
authors: L
authors: L
authors: Feng
authors: M
authors: M
authors: Said
authors: M
authors: M
authors: Dayton
mesh_terms: D001741:Black or African American; D000890:Anti-Infective Agents / Q000008:administration & dosage*; D001711:Biotransformation; D016009:Chi-Square Distribution; D003022:Clotrimazole / Q000008:administration & dosage*; D054796:Drug Dosage Calculations; D004347:Drug Interactions; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation / Q000009:adverse effects / Q000401:mortality; D015999:Multivariate Analysis; D009173:Mycophenolic Acid / Q000008:administration & dosage; D011241:Prednisone / Q000008:administration & dosage; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D016559:Tacrolimus / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D044465:White People
chemical_list: D000890:Anti-Infective Agents; D007166:Immunosuppressive Agents; D003022:Clotrimazole; D009173:Mycophenolic Acid; D011241:Prednisone; D016559:Tacrolimus