A clinical survey on the electrocardiogram after intravenous granisetron hydrochloride administration in clinically normal dogs


Keywords:
Granisetron hydrochloride QTc JTc Electrocardiogram Dog
H GHAEMI
H SALARI SEDIGH
M SELK GHAFFARI
Abstract

Cardiac side effect of 5-hydroxytryptamine-3 receptor antagonists has been a concern for clinicians. There is a substantial need for greater clarity about the safety of granisetron hydrochloride, an antiemetic agent of this class used in oncological and parvoviral gastroenteritis with acute vomiting in dogs. This study aimed to assess the electrocardiographic effects of a single dose of intravenous granisetron. We randomly assigned 16 adult crossbreed female healthy dogs into two groups of intervention and control and injected them intravenously with granisetron and normal saline, respectively, at a dose of 0.5 ml/kg over one minute. Standard electrocardiography (ECG) was recorded at the baseline, as well as 5, 15, 30, 60, 120, 360, and 720 minutes after the intervention. Heart rate and ECG parameters (PR intervals, QRS duration, ST-segment, T-wave amplitudes, QT, JT, QTc and JTc intervals) were evaluated in lead II.No significant difference was observed between the intervention and the control groups in any of the measured variables at any of the time-points. Mean values of measured parameters showed no significant difference compared with baseline values in the control group, while the granisetron group saw statistically significant but clinically asymptomatic changes in heart rate, PR, QRS, QT, JT, and QTc at different time-points, compared to the baseline values (P<0.05). In conclusion, Granisetron administration was not associated with clinically significant adverse effects on ECG variables or heart rate. Thus, it can be regarded as a relatively safe drug.

Article Details
  • Section
  • Research Articles
Downloads
Download data is not yet available.
References
Boike SC, ILson B, Zariffa N, Jorkasky DK (1997) Cardiovascular effects of iv granisetron at two administration rates and of ondansetron in healthy adults American journal of health-system pharmacy 54:1172-1176.
Buyukavci M, Olgun H, Ceviz N (2005) The effects of ondansetron and granisetron on electrocardiography in children receiving chemotherapy for acute leukemia American journal of clinical oncology 28:201-204.
Cakir F, Yapar O, Canpolat C, Akalin F, Berrak S (2012) Cardiac effects of granisetron in a prospective crossover randomized dose comparison trial Supportive Care in Cancer 20:2451-2457.
Chevallier B (1993) on behalf of the Granisetron Study Group: The control of acute cisplatin-induced emesis. A comparative study of granisetron and a combination regimen of high-dose metoclopramide and dexamethasone Br J Cancer 68:176-180.
Coop AJ (2003) Comment: electrocardiographic and cardiovascular effects of the 5-hydroxytryptamine-3 receptor antagonists Annals of Pharmacotherapy 37:1918-1918.
Dennis S, Wotton P, Boswood A, Flaherty D (2007) Comparison of the effects of thiopentone and propofol on the electrocardiogram of dogs The Veterinary Record 160:681-686.
Ghaffari MS, Moghaddassi AP, Khorami N (2010) The acute effects of ondansetron on the electrocardiogram in clinically normal dogs Comparative clinical pathology 19:499-502.
Goddard A, Leisewitz AL (2010) Canine parvovirus Veterinary Clinics: Small Animal Practice 40:1041-1053.
Gomez-de-Segura IA, Grande AG, De Miguel E (1998) Antiemetic effects of Lerisetron in radiation-induced emesis in the dog Acta Oncologica 37:759-763.
Gralinski MR (2003) The dog’s role in the preclinical assessment of QT interval prolongation Toxicologic pathology 31:11-16.
Gregory RE, Ettinger DS (1998) 5-HT3 receptor antagonists for the prevention of chemotherapy-induced nausea and vomiting Drugs 55:173-189.
Grunberg SM (1993) Potential for combination therapy with the new antiserotonergic agents European Journal of Cancer 29:S39-S41.
Harris DG (2010) Nausea and vomiting in advanced cancer British medical bulletin 96:175-185.
Hsu ES (2010) A review of granisetron, 5-hydroxytryptamine3 receptor antagonists, and other antiemetics American journal of therapeutics 17:476-486.
Hunt TL, Cramer M, Shah A, Stewart W, Benedict CR, Hahne WF (1995) A Double-Blind, Placebo-Controlled, Dose-Ranging Safety Evaluation of Single-Dose Intravenous Dolasetron in Healthy Male Volunteers The Journal of Clinical Pharmacology 35:705-712.
Janelsins MC, Tejani MA, Kamen C, Peoples AR, Mustian KM, Morrow GR (2013) Current pharmacotherapy for chemotherapy-induced nausea and vomiting in cancer patients Expert opinion on pharmacotherapy 14:757-766.
Jantunen IT, Kataja VV, Muhonen TT, Parviainen T (1996) Effects of granisetron with doxorubicin or epirubicin on ECG intervals Cancer chemotherapy and pharmacology 37:502-504.
Keefe DL (2002) The cardiotoxic potential of the 5-HT3 receptor antagonist antiemetics: is there cause for concern? The Oncologist 7:65-72.
Kuryshev YA, Brown AM, Wang L, Benedict CR, Rampe D (2000) Interactions of the 5-hydroxytryptamine 3 antagonist class of antiemetic drugs with human cardiac ion channels Journal of Pharmacology and Experimental Therapeutics 295:614-620.
Mason J, Moon TE, O’Boyle E, Dietz AJ (2013) Comparison of the effects of subcutaneous APF530, intravenous granisetron, moxifloxacin, and placebo on the QT interval in humans. American Society of Clinical Oncology,
Mason JW, Moon TE, O’Boyle E, Dietz A (2014) A randomized, placebo-controlled, four-period crossover, definitive QT study of the effects of APF530 exposure, high-dose intravenous granisetron, and moxifloxacin on QTc prolongation Cancer management and research 6:181.
Mason JW, Selness DS, Moon TE, O’Mahony B, Donachie P, Howell J (2012) Pharmacokinetics and repolarization effects of intravenous and transdermal granisetron Clinical Cancer Research 18:2913-2921.
Nandi S, Kumar M (2010) Canine parvovirus: current perspective Indian Journal of Virology 21:31-44.
Navari RM, Koeller JM (2003) Electrocardiographic and cardiovascular effects of the 5-hydroxytryptamine3 receptor antagonists Annals of Pharmacotherapy 37:1276-1286.
Pınarlı F, Elli M, Daǧdemir A, Baysal K, Acar S (2006) Electrocardiographic findings after 5-HT3 receptor antagonists and chemotherapy in children with cancer Pediatric blood & cancer 47:567-571.
Schnell FM (2003) Chemotherapy-induced nausea and vomiting: the importance of acute antiemetic control The oncologist 8:187-198.
Spartinou A, Nyktari V, Papaioannou A (2017) Granisetron: a review of pharmacokinetics and clinical experience in chemotherapy induced-nausea and vomiting Expert opinion on drug metabolism & toxicology 13:1289-1297.
Tricco AC et al. (2016) Comparative safety and effectiveness of serotonin receptor antagonists in patients undergoing chemotherapy: a systematic review and network meta-analysis BMC Medicine 14:216 doi:10.1186/s12916-016-0761-9
Williams PD, Cohen ML, Turk JA (1991) Electrocardiographic effects of zatosetron and ondansetron, two 5HT3 receptor antagonists, in anesthetized dogs Drug development research 24:277-284.
Woods C, Pollock R, Carmichael L (1980) Canine parvoviral enteritis .
Journal of the American Animal Hospital Association 16:171-179
Xiao L, Zhang L, Han W, Wang Z, Nattel S (2006) Sex-based transmural differences in cardiac repolarization and ionic-current properties in canine left ventricles American Journal of Physiology-Heart and Circulatory Physiology 291:H570-H580.
Yamakuni H et al. (2000) Probable Involvement of the 5-Hydroxytryptamine4Receptor in Methotrexate-Induced Delayed Emesis in Dogs Journal of Pharmacology and Experimental Therapeutics 292:1002-1007.