Evaluation of tacrolimus abbreviated area-under-the-curve monitoring in renal transplant patients who are potentially at risk for adverse events.
In a cohort of 32 renal transplant patients who are potentially at risk for adverse events, we compared tacrolimus (TAC) abbreviated AUC values calculated by a method developed in Asians (AUCw) with those derived for Caucasians (AUCa). The relationships between TAC trough (C0), abbreviated AUC, and biopsy results were also assessed. Forty-eight AUCs and 15 associated biopsies were evaluated. For AUCs obtained only from Caucasian patients, median AUCw value was lower than that of AUCa (104 vs. 115 ng×h/mL, n=29, p<0.0001). AUCs obtained from the two methods for all patients correlated with C0 (rs>0.72, n=48, p<0.0001). Median AUCw (72.9 vs. 174 ng×h/mL, p=0.043) and AUCa (81.0 vs. 203 ng×h/mL, p=0.043) were lower in patients experiencing biopsy-proven acute rejection (AR) than those with normal histology. C0 tended to be lower in biopsies showing AR>6 months post-transplant (5.80 vs. 11.0 ng/mL, p=0.110). Thus, lower abbreviated AUCs were obtained for Caucasians using a method developed in Asians. C0 correlated well with abbreviated AUCs. Lower C0 and AUC appeared to be associated with biopsy-proven AR>6 months post-transplant. Further prospective evaluation of TAC AUC and C0 monitoring in a larger cohort of patients is warranted.
Hon
Yuen Yi
YY
Pharmacy Department, Clinical Center, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. chon@cc.nih.gov
Chamberlain
Christine E
CE
Kleiner
David E
DE
Ring
Michael S
MS
Hale
Douglas A
DA
Kirk
Allan D
AD
Mannon
Roslyn B
RB
D000293:Adolescent; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D016903:Drug Monitoring; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D015996:Survival Rate; D016559:Tacrolimus / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D007166:Immunosuppressive Agents; D016559:Tacrolimus