Pharmacokinetics of Digoxin Cross-Reacting Substances in Patients With Acute Yellow Oleander (Thevetia peruviana) Poisoning, Including the Effect of Activated Charcoal

Abstract

Intentional self-poisonings with seeds from the yellow oleander tree (Thevetia peruviana) are widely reported. Activated charcoal has been suggested to benefit patients with yellow oleander poisoning by reducing absorption and/or facilitating elimination. Two recent randomised controlled trials (RCTs) assessing the efficacy of activated charcoal reported conflicting outcomes in terms of mortality. The effect of activated charcoal on the pharmacokinetics of Thevetia cardenolides has not been assessed. This information may be useful for determining whether further studies are necessary. Serial blood samples were obtained from patients enrolled in a RCT assessing the relative efficacy of single dose (SDAC) and multiple doses (MDAC) of activated charcoal compared to no activated charcoal (NoAC). The concentration of Thevetia cardenolides was estimated using a digoxin immunoassay. The effect of activated charcoal on cardenolide pharmacokinetics was compared between treatment groups using the AUC 24 , the 24h Mean Residence Time (MRT 24 ), and regression lines obtained from serial concentration points adjusted for exposure. Erratic and prolonged absorption patterns were noted in each patient group. The apparent terminal half-life was highly variable, with a median time of 42.9h. There was a reduction in MRT 24 and the apparent terminal half-life estimated from linear regression in patients administered activated charcoal compared to the control group (NoAC). This effect was approximately equal in patients administered MDAC or SDAC. Activated charcoal appears to favourably influence the pharmacokinetic profile of Thevetia cardenolides in patients with acute self-poisoning, which may have clinical benefits. Given the conflicting clinical outcomes noted in previous RCTs, this mechanistic data supports the need for further studies to determine whether a subgroup of patients (eg. those presenting soon after poisoning) will benefit from activated charcoal.

Rapid Detection of Oleander Poisoning by Digoxin III, a New Digoxin Assay

“…13,14 Recently, the pharmacokinetics of digoxin cross-reacting substances in patients poisoned with oleander was studied using the FPIA for digoxin. 18 In recent years, the use of complementary and herbal medicines has become more popular with the general population and several herbal products also contain oleander extract. Oleander extract has been shown to have selective cytotoxicity to tumor cells as opposed to normal cells, and Anvirzel (Ozelle Pharmaceuticals, San Antonio, TX), a patented medicine prepared from oleander, is in a clinical trial as a potential anticancer drug.…”

Eating seeds from the ‘be still’ tree, yet having lucky nut poisoning: a case of acute yellow oleander poisoning

“…In addition to these symptoms, patients can also present with cardiac arrhythmias ranging from sinus bradycardia to third degree atrioventricular block 3 4. These effects are derived from the structural and chemical similarities between the yellow oleander cardenolide-oleandrin and digitalis cardenolides derived from foxglove 5. These chemical similarities allow for some cross reactivity and detection by immunoassays utilised for measuring serum digoxin levels, with variable sensitivities 6 7.…”

“…These chemical similarities allow for some cross reactivity and detection by immunoassays utilised for measuring serum digoxin levels, with variable sensitivities 6 7. Ingestion of any part of the plant can result in poisoning with variable pharmacokinetics depending on the cardiac glycoside concentration of the different parts of the plant and the time following ingestion 3 5. There are reports of poisonous ingestion ranging from herbal teas to ingestion of a meal containing snail stew from a snail tissue with traces of oleandrin 8 9.…”

Dogbane Family and Cardenolides

“…The effi cacy of digoxin -specifi c Fab fragments for yellow oleander poisoning is variable, with improvement of the cardiac abnormalities in some, but not all patients with serious yellow oleander poisoning. 51 59 Her rhythm did not revert to normal sinus rhythm until 16 hours after ingestion despite the administration of an additional 190 mg digoxin -specifi c Fab antibody fragments.…”

“…51 The apparent terminal half -life of Thevetia cardenolides as estimated by a digoxin immunoassay in patients receiving supportive care and no activated charcoal was also highly variable with a median time of 42.9 hours (range: 13.27 -94.24 hours). Toxicokinetic data from a clinical study of 104 patients with Thevetia intoxication indicated that the absorption of Thevetia cardenolides is highly variable and prolonged with the time to maximum concentration exceeding 24 hours in some patients.…”