[Therapeutic drug monitoring of immunosuppresants].
The pharmacokinetics and pharmacodynamics of tacrolimus were evaluated in the pediatric recipients of living-related liver transplant. The mean clearance for tacrolimus was estimated with large interindividual variability and was shown to change as a function of days after operation. The therapeutic blood concentration of tacrolimus ranges were concerned from nearly 10 to 20 ng/ml. We have examined whether the expression levels of the intestinal absorptive barriers, MDR1 gene product P-glycoprotein and cytochrome P450 IIIA4(CYP3A4), correlate with the trough levels of orally administered tacrolimus in a recipient of small bowel transplant for 4 months. Both the MDR1 and CYP3A4 mRNA levels changed markedly through out this period. The tacrolimus concentration/dose ratio correlated well with the mRNA expression level of MDR1, but not CYP3A4. Intestinal P-glycoprotein rather than CYP3A4 is a good probe to predict the intraindividual variation in the tacrolimus pharmacokinetics.
Hashida
T
T
Department of Pharmacy, Kyoto University Hospital, Kyoto 606-8507.
Inui
K
K
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D002648:Child; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D016903:Drug Monitoring; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D007421:Intestine, Small / Q000637:transplantation; D016031:Liver Transplantation; D006899:Mixed Function Oxygenases / Q000378:metabolism; D016559:Tacrolimus / Q000493:pharmacokinetics*; D013810:Therapeutic Equivalency
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007166:Immunosuppressive Agents; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D016559:Tacrolimus