Ondansetron, clinical development for postoperative nausea and vomiting: current studies and future directions

Abstract

SummaryThe clinical development of ondansetron for the prevention and treatment of postoperative nausea and vomiting has been progressing for 5 years, and continues as new directions of research are being addressed. Large multicentre studies have demonstrated the eficacy of ondansetron in the prevention and treatment of postoperative nausea and vomiting, but no large comparator studies have been reported. Several studies are now being undertaken to compare ondansetron with other currently used antiemetics such as droperidol and metoclopramide. assessing eficacy, safety, pharmacoeconomic. and quality of fife parameters. The majority of studies to date have been performed in gynaecological surgery patients receiving general anaesthesia-a population that experiences a high incidence of postoperative nausea and vomiting. Clinical development of ondansetron is therefore progressing to establish its eficacy in a wider surgical population, including paediatrics, the elderly, nongynaecological surgery, and as retreatment in patients with failed prophylactic antiemetic therapy. Key wordsPharmacology; ondansetron. Vomiting; antiemetics.Ondansetron is a selective antagonist of the actions of 5-hydroxytryptamine (5-HT; serotonin) at the 5-HT1 receptor [I], and was the first drug in this class to be introduced for the clinical management of emesis associated with chemotherapy and radiotherapy. The antiemetic activity of ondansetron is believed to be mediated through blockade of the SHT, receptors found on vagal afferent terminals and located centrally in the area postrema [1,2].Postoperative nausea and vomiting (PONV) is one of the more common undesirable consequences of surgery [3]. Its incidence is highly variable, with reported rates averaging approximately 30% during the 24 h following surgery [4]. The aetiology of PONV is complex and is dependent on a variety of factors, including the patient characteristics, type of surgery, type of anaesthetic, and postoperative course, including drugs employed for pain management (e.g. opioids) [5]. The exact pathophysiology of PONV is not known; however, common pathways and neurotransmitters probably exist between the neuronal circuits involved in the manifestation of PONV and other causes of emesis, such as in cancer patients receiving emetogenic chemotherapy or radio therapy.Ondansetron has been in clinical development for the prevention and treatment of PONV since 1988. Large multicentre studies have demonstrated that intravenously administered ondansetron 4 mg is effective in preventing [6] and treating established PONV [7l. In addition, a single oral dose of ondansetron 16 mg has recently been shown to be an effective prophylactic antiemetic [8].The clinical development of ondansetron for use in PONV is continuing, but many important clinical and scientific issues still need to be addressed. These issues and other areas for future clinical research with ondansetron are discussed in this paper. Comparator studiesTo date, all of the large multicentre studies of ondansetron in P...

There is no Difference in the Incidence of Postoperative Nausea and Vomiting (PONV) When Ondansetron (ZOFRAN) is Administered Prior to Induction or Emergence from General Anesthesia

“…The elimination half-life for ondansetron is approximately 3.5 to 5.5 hours in adults (ondansetron package insert, 1995). Because of the relatively short half-life, it may be reasonable to administer it near the end of the surgical procedure, especially for those longer than 2 hours duration (Joslyn, 1994). 4 …”

“…Currently, there are no treatments to prevent the stimulation of mechanoreceptors and touch receptors, however, there are a variety of medications which act as antagonists for emetic agents on chemoreceptors (Joslyn, 1994). Ondansetron, a newer drug used in the treatment of PONV, acts as an antagonist for emetics which act upon the CTZ via a specific class of serotonin receptor, the 5-hydroxytryptamine subtype 3 (5HT3) receptor.…”

“…administration is yet to be determined (Joslyn, 1994). The variability in the peak effect lends to the difficulty in determining the most appropriate time to administer ondansetron.…”

“…A comparison between postoperative pain medications administered to the two groups were evaluated as being used or not used. It is unclear if opioids prevent pain and therefore reduce the nausea associated with pain or if they are in themselves emetic agents which would cause PONV (Kenny, 1994;Joslyn, 1994). We assessed their use for postoperative pain control in the PACU to determine if there was an even distribution of their use between the two groups.…”

Quantitative determination of ondansetron in human plasma by enantioselective liquid chromatography-tandem mass spectrometry

“…1A), is a highly selective and potent 5-hydroxytryptamine type 3 (5-HT 3 ) receptor antagonist. It is effective in the treatment of nausea and vomiting during cancer chemotherapy and radiotherapy, and has reported anxiolytic and neuroleptic properties [1][2][3][4]. Ondansetron was the first member of 5-HT3 receptor antagonists to be marketed as a racemate mixture of the R-(−) and S-(+) enantiomers.…”