Excess fluid distribution affects tacrolimus absorption in peritoneal dialysis patients
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
Excess fluid distribution is a common disorder in peritoneal dialysis (PD) patients. Tacrolimus malabsorption may also occur in PD patients, and may lead to acute allograft rejection after transplantation. The purpose of this study was to evaluate the relationship between tacrolimus pharmacokinetics and excess fluid distribution according to pre-transplant dialysis modality.
We retrospectively analyzed 41 adult living-donor kidney transplantations, including nine PD patients and 32 hemodialysis (HD) patients. We examined tacrolimus pharmacokinetics in the peri-operative period and determined the association between the tacrolimus absorption rate and body weight reduction. The absorption efficacy of tacrolimus was evaluated as the dose-normalized tacrolimus absorption rate. Tacrolimus concentrations in PD effluent were measured by high-performance liquid chromatography.
The tacrolimus absorption rate on the day before kidney transplantation tended to be lower in PD patients than in HD patients; however, the rate improved after kidney transplantation and was similar in both groups of patients. The peak tacrolimus concentration time was later in PD patients than in HD patients. The body weight reduction after kidney transplantation was greater in PD patients than in HD patients, and was significantly associated with the change in tacrolimus absorption rate (p = 0.04, r = 0.32). Only 0.002 % of the oral tacrolimus dose was removed by PD itself.
Excess fluid distribution in PD patients appears to contribute to tacrolimus malabsorption rather than PD itself. We should consider the risk of tacrolimus malabsorption in patients with possible excess fluid distribution, particularly in PD patients.
- Laupacis A, Keown P, Pus N, et al. A study of the quality of life and cost-utility of renal transplantation. Kidney Int. 1996;50:235–42. CrossRef
- Edwards EB, Bennett LE, Cecka JM. Effect of HLA matching on the relative risk of mortality for kidney recipients: a comparison of the mortality risk after transplant to the mortality risk of remaining on the waiting list. Transplantation. 1997;64:1274–7. CrossRef
- Burra P, De Bona M. Quality of life following organ transplantation. Transpl Int. 2007;20:397–409. CrossRef
- Snyder JJ, Kasiske BL, Gilbertson DT, Collins AJ. A comparison of transplant outcomes in peritoneal and hemodialysis patients. Kidney Int. 2002;62:1423–30. CrossRef
- Konings CJ, Kooman JP, Schonck M, et al. Fluid status, blood pressure, and cardiovascular abnormalities in patients on peritoneal dialysis. Perit Dial Int. 2002;22:477–87.
- John B, Tan BK, Dainty S, Spanel P, Smith D, Davies SJ. Plasma volume, albumin, and fluid status in peritoneal dialysis patients. Clin J Am Soc Nephrol. 2010;5:1463–70. CrossRef
- Plum J, Schoenicke G, Kleophas W, et al. Comparison of body fluid distribution between chronic haemodialysis and peritoneal dialysis patients as assessed by biophysical and biochemical methods. Nephrol Dial Transplant. 2001;16:2378–85. CrossRef
- Van Biesen W, Williams JD, Covic AC, et al. Fluid status in peritoneal dialysis patients: the European Body Composition Monitoring (EuroBCM) study cohort. PLoS One. 2011;6:e17148. CrossRef
- Crone CC, Gabriel GM. Treatment of anxiety and depression in transplant patients: pharmacokinetic considerations. Clin Pharmacokinet. 2004;43:361–94. CrossRef
- Morrissey PE, Gohh R, Shaffer D, et al. Correlation of clinical outcomes after tacrolimus conversion for resistant kidney rejection or cyclosporine toxicity with pathologic staging by the Banff criteria. Transplantation. 1997;63:845–8. CrossRef
- Coto E, Tavira B. Pharmacogenetics of calcineurin inhibitors in renal transplantation. Transplantation. 2009;88:S62–7. CrossRef
- Mourad M, Wallemacq P, De Meyer M, et al. Biotransformation enzymes and drug transporters pharmacogenetics in relation to immunosuppressive drugs: impact on pharmacokinetics and clinical outcome. Transplantation. 2008;85:S19–24. CrossRef
- Anglicheau D, Verstuyft C, Laurent-Puig P, et al. Association of the multidrug resistance-1 gene single-nucleotide polymorphisms with the tacrolimus dose requirements in renal transplant recipients. J Am Soc Nephrol. 2003;14:1889–96. CrossRef
- Tsuchiya N, Satoh S, Tada H, et al. Influence of CYP3A5 and MDR1 (ABCB1) polymorphisms on the pharmacokinetics of tacrolimus in renal transplant recipients. Transplantation. 2004;78:1182–7. CrossRef
- MacPhee IA, Fredericks S, Tai T, et al. The influence of pharmacogenetics on the time to achieve target tacrolimus concentrations after kidney transplantation. Am J Transplant. 2004;4:914–9. CrossRef
- Bekersky I, Dressler D, Mekki Q. Effect of time of meal consumption on bioavailability of a single oral 5 mg tacrolimus dose. J Clin Pharmacol. 2001;41:289–97. CrossRef
- Kimikawa M, Kamoya K, Toma H, Teraoka S. Effective oral administration of tacrolimus in renal transplant recipients. Clin Transplant. 2001;15:324–9. CrossRef
- Sofue T, Inui M, Kiyomoto H, et al. Pre-existing arteriosclerotic intimal thickening in living-donor kidneys reflects allograft function. Am J Nephrol. 2012;36:127–35. CrossRef
- Jaeger JQ, Mehta RL. Assessment of dry weight in hemodialysis: an overview. J Am Soc Nephrol. 1999;10:392–403.
- Solez K, Colvin RB, Racusen LC, et al. Banff 07 classification of renal allograft pathology: updates and future directions. Am J Transplant. 2008;8:753–60. CrossRef
- Rudant E, Bezie Y, Bonhomme-Faivre L, et al. Study of the correlation between MEIA and ELISA methods for FK 506 determination in liver transplant recipients. J Clin Pharm Ther. 1997;22:135–40. CrossRef
- Macphee IA, Fredericks S, Mohamed M, et al. Tacrolimus pharmacogenetics: the CYP3A5*1 allele predicts low dose-normalized tacrolimus blood concentrations in whites and South Asians. Transplantation. 2005;79:499–502. CrossRef
- Iwasaki K, Shiraga T, Nagase K, et al. Isolation, identification, and biological activities of oxidative metabolites of FK506, a potent immunosuppressive macrolide lactone. Drug Metab Dispos. 1993;21:971–7.
- Chen YL, Hirabayashi H, Akhtar S, Pelzer M, Kobayashi M. Simultaneous determination of three isomeric metabolites of tacrolimus (FK506) in human whole blood and plasma using high performance liquid chromatography–tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2006;830:330–41. CrossRef
- Shimomura M, Masuda S, Saito H, et al. Roles of the jejunum and ileum in the first-pass effect as absorptive barriers for orally administered tacrolimus. J Surg Res. 2002;103:215–22. CrossRef
- Tamura S, Tokunaga Y, Ibuki R, Amidon GL, Sezaki H, Yamashita S. The site-specific transport and metabolism of tacrolimus in rat small intestine. J Pharmacol Exp Ther. 2003;306:310–6. CrossRef
- Sattler M, Guengerich FP, Yun CH, Christians U, Sewing KF. Cytochrome P-450 3A enzymes are responsible for biotransformation of FK506 and rapamycin in man and rat. Drug Metab Dispos. 1992;20:753–61.
- Excess fluid distribution affects tacrolimus absorption in peritoneal dialysis patients
Clinical and Experimental Nephrology
Volume 17, Issue 5 , pp 743-749
- Cover Date
- Print ISSN
- Online ISSN
- Springer Japan
- Additional Links
- Peritoneal dialysis
- Excess fluid distribution
- Tacrolimus pharmacokinetics
- Living-donor kidney transplantation
- Industry Sectors
- Author Affiliations
- 1. Division of Nephrology and Dialysis, Department of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-Cho, Kita-Gun, Kagawa, 761-0793, Japan
- 2. Department of Urology, Faculty of Medicine, Kagawa University, Kagawa, Japan
- 3. Division of Nephrology, Endocrinology and Vascular Medicine, Department of Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
- 4. Department of Pharmacy, Kagawa University Hospital, Kagawa, Japan
- 5. Shiga Pharmaceutical Association Proof Center, Kusatsu, Japan
- 6. Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, Japan