Effect of intestinal P‐glycoprotein on daily tacrolimus trough level in a living‐donor small bowel recipient

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. By using a competitive...

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Bibliographic Details
Published in:Clinical pharmacology and therapeutics 2000-07, Vol.68 (1), p.98-103
Main Authors: Masuda, Satohiro, Uemoto, Shinji, Hashida, Tohru, Inomata, Yukihiro, Tanaka, Koichi, Inui, Ken‐ichi
Format: Article
Language:English
Subjects:
ATP Binding Cassette Transporter, Subfamily B, Member 1 - genetics
ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism
Biological and medical sciences
Child, Preschool
Cytochrome P-450 CYP3A
Cytochrome P-450 Enzyme System - genetics
Female
Humans
Ileum - metabolism
Ileum - transplantation
Immunomodulators
Immunosuppressive Agents - blood
Immunosuppressive Agents - pharmacokinetics
Intestinal Absorption
Medical sciences
Mixed Function Oxygenases - genetics
Pharmacology. Drug treatments
Polymerase Chain Reaction
RNA
RNA, Messenger - chemistry
Tacrolimus - blood
Tacrolimus - pharmacokinetics
Transplantation, Homologous
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Summary: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. By using a competitive polymerase chain reaction, the expression of MDR1 messenger RNA (mRNA) and CYP3A4 mRNA by intestinal cells in a part of the mucosa biopsy specimen was evaluated. The average mRNA expression levels of MDR1 and CYP3A4 were 8.6 and 39.6 amol/μg total RNA, respectively. Both the MDR1 and CYP3A4 mRNA levels changed markedly throughout this period. The tacrolimus concentration/dose ratio correlated well with the mRNA expression level of MDR1, but not CYP3A4. These results suggested that intestinal P‐glycoprotein rather than CYP3A4 is a good probe to predict the intraindividual variation in the tacrolimus pharmacokinetics during immunosuppressant therapy after small bowel transplantation. Clinical Pharmacology & Therapeutics (2000) 68, 98–103; doi: 10.1067/mcp.2000.107912
ISSN:0009-9236
1532-6535
DOI:10.1067/mcp.2000.107912