Alterations of CYP3A4 and P-glycoprotein activity in vivo with time in renal graft recipients

Lemahieu, Wim P. D.; Maes, Bart D.; Verbeke, Kirstin; Vanrenterghem, Yves F. Ch.
July 2004
Kidney International;Jul2004, Vol. 66 Issue 1, p433
Academic Journal
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 14C-excretion dynamics in breath and urine after oral and intravenous administration of [N-methyl-14C]-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.


Related Articles

  • Lamivudine.  // Reactions Weekly;11/24/2007, Issue 1179, p22 

    The article describes the case of a 31-year old patient who developed acute rejection of a kidney transplant while receiving lamivudine. Biopsy revealed the cause of the acute rejection of the kidney transplant. The patient's kidney function and clinical state improved after receiving...

  • Impact of the CYP3A5, CYP3A4, COMT, IL-10 and POR Genetic Polymorphisms on Tacrolimus Metabolism in Chinese Renal Transplant Recipients. Li, Chuan-Jiang; Li, Liang; Lin, Li; Jiang, Hai-Xia; Zhong, Ze-Yan; Li, Wei-Mo; Zhang, Yan-Jun; Zheng, Ping; Tan, Xu-Hui; Zhou, Lin // PLoS ONE;Jan2014, Vol. 9 Issue 1, p1 

    Tacrolimus is a widely used immunosuppressive drug for preventing the rejection of solid organ transplants. The efficacy of tacrolimus shows considerable variability, which might be related to genetic variation among recipients. We conducted a retrospective study of 240 Chinese renal transplant...

  • Budget impact of switching from an immediate-release to a prolonged-release formulation of tacrolimus in renal transplant recipients in the UK based on differences in adherence. Muduma, Gorden; Odeyemi, Isaac; Pollock, Richard F.; Smith-Palmer, Jayne // Patient Preference & Adherence;2014, Vol. 8, p391 

    Background and aims: Advagraf is a once-daily prolonged-release formulation of tacrolimus with proven noninferiority to Prograf, a twice-daily immediate-release formulation of tacrolimus, in biopsy-proven acute rejection, graft survival and patient survival in renal transplant recipients....

  • Tacrolimus.  // Reactions Weekly;9/6/2008, Issue 1218, p31 

    The article describes the case of a 28-year-old woman who developed chronic diarrhoea and elevated creatinine levels during tacrolimus treatment. The patient with a renal transplant was treated with tacrolimus, azathioprine and prednisolone. During the first 4 months of antitubercular treatment,...

  • Tacrolimus interaction.  // Reactions Weekly;1/15/2005, Issue 1034, p13 

    Discusses research being done on the role of concomitant diltiazem, ritonavir and saquinavir in tacrolimus concentration. Reference to a study by G. Hardy et al., published in the October 2004 issue of the "European Journal of Clinical Pharmacology"; Drugs received by the patient for...

  • Tacrolimus.  // Reactions Weekly;9/6/2008, Issue 1218, p31 

    The article describes the case of an 8.5-year-old male renal transplant recipient who developed brachial neuritis during immunosuppression with tacrolimus. It notes that magnetic resonance imaging (MRI) results were suggestive of myelitis and right brachial plexitis. The tacrolimus dosage for...

  • Tacrolimus.  // Reactions Weekly;1/12/2008, Issue 1184, p33 

    The article describes the case of two renal transplant recipients who developed chronic sensorimotor polyneuropathy during immunosuppression with tacrolimus. An overview of the clinical history of the patient is presented, as well as a discussion on the physical and laboratory examinations...

  • CYP3A5 Genotype Markedly Influences the Pharmacokinetics of Tacrolimus and Sirolimus in Kidney Transplant Recipients. Renders, L.; Frisman, M.; Ufer, M.; Mosyagin, I.; Haenisch, S.; Ott, U.; Caliebe, A.; Dechant, M.; Braun, F.; Kunzendorf, U.; Cascorbi, I. // Clinical Pharmacology & Therapeutics;Feb2007, Vol. 81 Issue 2, p228 

    It is currently not clear whether the concentration–time curves of the immunosuppressants differ with respect to the CYP3A5, MDR1, or MRP2 genotype in dose-adapted stable kidney transplant patients. Dose/trough concentration ratios were obtained in 134 tacrolimus and 20 sirolimus-treated...

  • Tacrolimus.  // Reactions Weekly;5/21/2011, Issue 1352, p35 

    The article describes the case of a 20-year-old woman with a stable renal transplantation who experienced biopsy-proven acute rejection after receiving the Prograf brand of tacrolimus.


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics