Objectives. Ondansetron is a 5-hydroxytryptamine (5-HT3, serotonin) receptor antagonist used as antiemetic prophylaxis preceding chemotherapy administration. Hypokalemia is a rare complication of ondansetron, which may be underreported due to confounding emesis and chemotherapy-induced tubulopathy. We performed a prospective cohort study to determine if ondansetron caused significant hypokalemia independently as a result of renal potassium wasting. Methods. Twelve patients were recruited, with ten completing the study. Blood and urine samples were collected before and after ondansetron administration in patients admitted for intravenous (IV) hydration and chemotherapy. Dietary histories and IV records were analyzed to calculate sodium and potassium balances. Results. We observed an expected drop in urine osmolality, an increase in urine sodium, but no statistically significant change in sodium or potassium balance before and after ondansetron. Conclusion. Ondansetron does not cause significant potassium wasting in appropriately hydrated and nutritionally replete patients. Careful monitoring of serum potassium is recommended in patients with chronic nutritional or volume status deficiencies receiving this medication. 1. Introduction Ondansetron is an antiemetic used as an adjunctive to chemotherapy in pediatric oncology patients. It is a selective 5-HT3 receptor antagonist which has an excellent safety profile and is efficacious [1, 2]. A side effect infrequently reported is the development of hypokalemia [3]. Hypokalemia may be a result of ondansetron itself [3–5], an effect of chemotherapy on renal tubular function [6], a result of emesis-induced alkalosis [7], or a combination of factors. Based on in vitro data, ondansetron has the capacity to cause hypokalemia by affecting renal tubular physiology [4]. Ondansetron acts at two levels in the nephron. First, at the level of the Loop of Henle, ondansetron downregulates the Na+-K+-2Cl-(NKCC2) cotransporter, which results in increased sodium delivery to the distal nephron. This in turn necessitates K+ excretion, via the ROMK potassium channel to facilitate the electroneutral reabsorption of sodium via the epithelial sodium channel (ENaC) from the distal nephron, leading to K+ wasting. Second, throughout the nephron, and in particular the distal tubule, ondansetron upregulates the Na+-K+ ATPase. This exacerbates the renal K wasting by lowering intracellular sodium levels in distal tubular cells expressing ENaC thereby further increasing tubular sodium entry at this segment. This ultimately requires
References
[1]
M. T. Holdsworth, D. W. Raisch, and J. Frost, “Acute and delayed nausea and emesis control in pediatric oncology patients,” Cancer, vol. 106, no. 4, pp. 931–940, 2006.
[2]
M. Aapro, “5-HT3-receptor antagonists in the management of nausea and vomiting in cancer and cancer treatment,” Oncology, vol. 69, no. 2, pp. 97–109, 2005.
P. Behnam-Motlagh, P. E. Sandstr？m, R. Henriksson, and K. Grankvist, “Diverging effects of 5-HT3 receptor antagonists ondansetron and granisetron on estramustine-inhibited cellular potassium transport,” Pharmacology and Toxicology, vol. 88, no. 5, pp. 244–249, 2001.
[5]
S. R. Turner and M. Pinsk, “Ondansetron-associated hypokalemia in a 2-year-old with pre-B-cell ALL,” Journal of Pediatric Hematology/Oncology, vol. 30, no. 1, pp. 58–60, 2008.
[6]
S. G. Cunningham, “Fluid and electrolyte disturbances associated with cancer and its treatment,” Nursing Clinics of North America, vol. 17, no. 4, pp. 579–593, 1982.
[7]
A. Khanna and N. A. Kurtzman, “Metabolic alkalosis,” Journal of Nephrology, vol. 19, no. 9, pp. S86–S96, 2006.
[8]
P. Behnam-Motlagh, P. E. Sandstr？m, R. Henriksson, and K. Grankvist, “Ondansetron but not granisetron affect cell volume regulation and potassium ion transport of glioma cells treated with estramustine phosphate,” Journal of Cancer Research and Clinical Oncology, vol. 128, no. 8, pp. 449–455, 2002.
[9]
Bodyventures, Diet and Fitness today: online health and fitness. Bodyventures, 2010 [updated 2010, cited October, 2010], http://www.dietandfitnesstoday.com/.
[10]
J. Rodriguez-Soriano, M. Ubetagoyena, and A. Vallo, “Transtubular potassium concentration gradient: a useful test to estimate renal aldosterone bio-activity in infants and children,” Pediatric Nephrology, vol. 4, no. 2, pp. 105–110, 1990.
[11]
M. G. Nicholls, “Side effects and metabolic effects of converting-enzyme inhibitors,” Clinical and Experimental Hypertension A, vol. 9, pp. 653–664, 1987.
[12]
B. F. Palmer, “A physiologic-based approach to the evaluation of a patient with hypokalemia,” American Journal of Kidney Diseases, vol. 56, no. 6, pp. 1184–1190, 2010.
[13]
S. N. Thornton, “Thirst and hydration: physiology and consequences of dysfunction,” Physiology and Behavior, vol. 100, no. 1, pp. 15–21, 2010.
[14]
R. H. Sterns, M. Cox, P. U. Feig, and I. Singer, “Internal potassium balance and the control of the plasma potassium concentration,” Medicine, vol. 60, no. 5, pp. 339–354, 1981.
[15]
G. J. Schwartz, L. P. Brion, and A. Spitzer, “The use of plasma creatinine concentration for estimating glomerular filtration rate in infants, children, and adolescents,” Pediatric Clinics of North America, vol. 34, no. 3, pp. 571–590, 1987.
[16]
M. I. Wilde and A. Markham, “Ondansetron: a review of its pharmacology and preliminary clinical findings in novel applications,” Drugs, vol. 52, no. 5, pp. 773–794, 1996.
[17]
F. Roila and A. Del Favero, “Ondansetron clinical pharmacokinetics,” Clinical Pharmacokinetics, vol. 29, no. 2, pp. 95–109, 1995.
