The aim of this study was to assess removal dynamics of paracetamol (PAR), as an extraordinary chromophore in spent dialysate, upon the optical monitoring of dialysis of end-stage renal disease patients with inflammation complications. Seven dialysis sessions of different patients were followed to whom PAR was used as a pain reliever or antipyretic. Spent dialysate was sampled hourly and analyzed using HPLC with MS/MS and UV detection. Quantitative calculations were made on the basis of the peak areas on the chromatograms at 280？nm for uric acid (UA) and 254？nm for PAR and its metabolites (PAR-M). Peaks of UA, PAR, PAR-glucuronide, and PAR-sulphate were identified on the basis of specific mass spectra. Removal of PAR was found to be proportional to that of uric acid if intake of the drug by patient occurred half a day before dialysis. But disturbances of the UV-absorbance curves at 280？nm were observed related to rise of UA concentration in spent dialysate when PAR was taken by patients in the course of dialysis. The mechanism of such relation remains unknown. It was concluded that possible benefits and risks of treatment of uremic patients with paracetamol-containing drugs may need to be reassessed. 1. Introduction Uric acid (UA) is known as a normal final product of human metabolism of purines, essential constituents of nucleic acids, and is normally excreted by kidney with urine [1]. High concentration of UA in serum often associates with severe chronic pathologies, such as arthritis, hypertension, and so forth [2]. Many recommendations have been published for such patients listing purine-rich food products to be avoided as well as some drugs, which are known to be associated with a raise of UA in blood, but paracetamol (PAR), a worldwide used analgesic and antipyretic drug [3], is not usually included into such lists. Paracetamol (PAR) is known as a potent enhancer of the effect of many other drugs [4] and its combination with analgesic drugs as pain reliever, including treatment of acute gout-like arthritis associated with high level of UA in blood [5]. Some observations have been published in the older literature concerning elevated analytical results of UA in serum following PAR administration, but this effect was found to be caused by interference of PAR with phosphotungstate reduction method of UA analysis only and an alternative uricase method did not confirm relationship between UA concentration and PAR administration [6, 7]. Since no strong limitation is known, PAR is dosed sometimes also to patients with renal failure as an analgesic or
References
[1]
B. álvarez-Lario and J. Macarrón-vicente, “Is there anything good in uric acid?” QJM, vol. 104, no. 12, Article ID hcr159, pp. 1015–1024, 2011.
[2]
T. R. Merriman, “Editorial,” Current Rheumatology Reviews, vol. 7, no. 2, pp. 94–96, 2011.
[3]
L. Zhao and G. Pickering, “Paracetamol metabolism and related genetic differences,” Drug Metabolism Reviews, vol. 43, no. 1, pp. 41–52, 2011.
[4]
A. Li Wan Po and W. Y. Zhang, “Systematic overview of co-proxamol to assess analgesic effects of addition of dextropropoxyphene to paracetamol,” British Medical Journal, vol. 315, no. 7122, pp. 1565–1571, 1997.
[5]
C. Y. Man, I. T. F. Cheung, P. A. Cameron, and T. H. Rainer, “Comparison of oral prednisolone/paracetamol and oral indomethacin/paracetamol combination therapy in the treatment of acute goutlike arthritis: a double-blind, randomized, controlled trial,” Annals of Emergency Medicine, vol. 49, no. 5, pp. 670–677, 2007.
[6]
P. Wilding and D. A. Heath, “Effect of paracetamol on uric acid determination,” Annals of Clinical Biochemistry, vol. 12, no. 4, pp. 142–144, 1975.
[7]
M. Smith and R. B. Payne, “Re-examination of effect of paracetamol on serum uric acid measured by phosphotungstic acid reduction,” Annals of Clinical Biochemistry, vol. 16, no. 2, pp. 96–99, 1979.
[8]
M. Luman, J. Jerotskaja, K. Lauri, and I. Fridolin, “Dialysis dose and nutrition assessment by optical on-line dialysis adequacy monitor,” Clinical Nephrology, vol. 72, no. 4, pp. 303–311, 2009.
[9]
A. Castellarnau, M. Werner, R. Günthner, and M. Jakob, “Real-time Kt/V determination by ultraviolet absorbance in spent dialysate: technique validation,” Kidney International, vol. 78, no. 9, pp. 920–925, 2010.
[10]
K. Lauri, J. Arund, J. Holmar, R. Tanner, M. Luman, and I. Fridolin, “Optical dialysis adequacy monitoring: small uremic toxins and contribution to UV-absorbance studied by HPLC,” in Progress in Hemodialysis—From Emergent Biotechnology to Clinical Practice, A. Carpi, C. Donadio, and G. Tramonti, Eds., pp. 143–160, InTech, 2011.
[11]
J. Jerotskaja, F. Uhlin, I. Fridolin, K. Lauri, M. Luman, and A. Fernstr？m, “Optical online monitoring of uric acid removal during dialysis,” Blood Purification, vol. 29, no. 1, pp. 69–74, 2010.
[12]
J. Arund, R. Tanner, F. Uhlin, and I. Fridolin, “Do only small uremic toxins—chromophores contribute to the online dialysis dose monitoring by UV absorbance,” Toxins, vol. 4, no. 10, pp. 849–861, 2012.
[13]
K. Lauri, R. Tanner, J. Jerotskaja, M. Luman, and I. Fridolin, “HPLC study of uremic fluids related to optical dialysis adequacy monitoring,” International Journal of Artificial Organs, vol. 33, no. 2, pp. 96–104, 2010.
[14]
A. K. Hewavitharana, S. Lee, P. A. Dawson, D. Markovich, and P. N. Shaw, “Development of an HPLC-MS/MS method for the selective determination of paracetamol metabolites in mouse urine,” Analytical Biochemistry, vol. 374, no. 1, pp. 106–111, 2008.
[15]
R. J. Johnson, P. Andrews, S. A. Benner, and W. Oliver, “Theodore E. Woodward award. The evolution of obesity: insights from the mid-Miocene,” Transactions of the American Clinical and Climatological Association, vol. 121, pp. 295–308, 2010.
[16]
M. Koelsch, R. Mallak, G. G. Graham et al., “Acetaminophen (paracetamol) inhibits myeloperoxidase-catalyzed oxidant production and biological damage at therapeutically achievable concentrations,” Biochemical Pharmacology, vol. 79, no. 8, pp. 1156–1164, 2010.
[17]
D. G. Wickens, A. G. Norden, J. Lunec, and T. L. Dormandy, “Fluorescence changes in human gamma-globulin induced by free-radical activity,” Biochimica et Biophysica Acta, vol. 742, no. 3, pp. 607–616, 1983.
[18]
Y. Y. Sautin, T. Nakagawa, S. Zharikov, and R. J. Johnson, “Adverse effects of the classic antioxidant uric acid in adipocytes: NADPH oxidase-mediated oxidative/nitrosative stress,” American Journal of Physiology, vol. 293, no. 2, pp. C584–C596, 2007.
[19]
R. Mohandas and R. J. Johnson, “Uric acid levels increase risk for new-onset kidney disease,” Journal of the American Society of Nephrology, vol. 19, no. 12, pp. 2251–2253, 2008.
[20]
R. P. Obermayr, C. Temml, G. Gutjahr, M. Knechtelsdorfer, R. Oberbauer, and R. Klauser-Braun, “Elevated uric acid increases the risk for kidney disease,” Journal of the American Society of Nephrology, vol. 19, no. 12, pp. 2407–2413, 2008.
[21]
F. C. Meotti, G. N. L. Jameson, R. Turner et al., “Urate as a physiological substrate for myeloperoxidase: implications for hyperuricemia and inflammation,” The Journal of Biological Chemistry, vol. 286, no. 15, pp. 12901–12911, 2011.
