Alterations of CYP3A4 and P-glycoprotein activity in vivo with time in renal graft recipients
| Autor: | Kirstin Verbeke, Bart Maes, Wim Lemahieu, Yves Vanrenterghem |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Nephrology
Male medicine.medical_specialty CYP3A4 Time Factors medicine.drug_class Urinary system P-glycoprotein Excretion Intestinal mucosa Cytochrome P-450 Enzyme System Internal medicine medicine Cytochrome P-450 CYP3A Humans ATP Binding Cassette Transporter Subfamily B Member 1 Postoperative Period Intestinal Mucosa Kidney business.industry breath test Kidney Transplantation Calcineurin Transplantation medicine.anatomical_structure Endocrinology Liver Case-Control Studies Corticosteroid Female business transplantation steroids |
| Zdroj: | Kidney international. 66(1) |
| ISSN: | 0085-2538 |
| Popis: | Alterations of CYP3A4 and P-glycoprotein activity in vivo with time in renal graft recipients. Background Catabolism by intestinal and hepatic cytochrome P450 3A4 (CYP3A4), and excretion by P-glycoprotein (PGP), has a major influence on oral bioavailability of calcineurin inhibitors. In this study, the activity of intestinal and hepatic CYP3A4 and PGP in vivo was assessed in renal transplant recipients during the first year after transplantation (Tx). Methods Stable Caucasian renal transplant patients were tested at 1 week, 3 months, and 1 year after Tx, and compared with the results obtained in drug-free healthy volunteers. Intestinal and hepatic CYP3A4 and PGP activity were determined by measurement of 14 C-excretion dynamics in breath and urine after oral and intravenous administration of [N-methyl- 14 C]-erythromycin. Results Compared with 1 week after Tx, intestinal and hepatic CYP3A4 activity significantly decreased at 3 months and 1 year after Tx (-33% and -45%; -7% and -33%, respectively). Compared with the healthy volunteers, intestinal and hepatic CYP3A4 activity of the patients was significantly increased at 1 week after Tx, but normalized at 1 year after Tx. A similar pattern, though not significant, was seen for intestinal PGP activity. Conclusion Phenotypic expression of hepatic and intestinal CYP3A4 was increased immediately after Tx, but gradually decreased to basal levels toward the end of the first year after Tx. The most plausible explanation for this evolution was the tapering of corticosteroid (CS) doses. These findings may also explain the increasing bioavailability of tacrolimus with time after Tx. |
| Databáze: | OpenAIRE |
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