Interindividual variation of maximal blood levels of tacrolimus after its oral administration in hematopoietic cell transplant recipients.
We investigated the pharmacokinetics of oral tacrolimus in 31 hematopoietic cell transplant recipients, identifying 2 subgroups based on the differences between C(0) (trough) and C(max) (maximal) levels: group A (n = 21; 68%) with a C(max)-C(0) value of <10 ng/mL, and group B (n = 10; 32%) with a C(max)-C(0) value of >or=10 ng/mL. Although the C(0) and C(12) values were not significantly different between the 2 groups, the mean area under the concentration curve for 12 hours (AUC(0-12)) was significantly greater in group B than group A (200.9 +/- 36.3 vs 155.1 +/- 43.1 ng.h/mL; P < .05), and the mean half-life was significantly shorter in group B than group A (13.55 +/- 6.70 vs 18.17 +/- 6.30 hours; P < .05). Thus after the oral administration of tacrolimus, we observed a notably high AUC due to high peak level, which we were unable to predict simply by measuring the trough level. A pharmacokinetic analysis of each patient was essential to optimize the oral tacrolimus dose.
Yamazaki
R
R
Division of Hematology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
Mori
T
T
Aisa
Y
Y
Kato
J
J
Nakamura
Y
Y
Nakazato
T
T
Mihara
A
A
Ikeda
Y
Y
Okamoto
S
S
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D001835:Body Weight; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D007938:Leukemia / Q000601:surgery; D008223:Lymphoma / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000601:surgery; D016559:Tacrolimus / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D055815:Young Adult
D007166:Immunosuppressive Agents; D016559:Tacrolimus