Biotransformation of the ipecac alkaloids cephaeline and emetine from ipecac syrup in rats

Abstract

The metabolism of cephaeline and emetine, which are the primary active components of ipecac syrup, were investigated in rats. Cephaeline-6'-O-glucuronide was found to be a biliary metabolite of cephaeline. Cephaeline (6'-O-demethylemetine) and 9-O-demethylemetine were observed to be enzyme-hydrolyzed biliary metabolites of emetine. Cephaeline was conjugated to glucuronide, while emetine was demethylated to cephaeline and 9-0-demethylemetine, and may be conjugated to glucuronides afterwards. Urine, feces and bile were collected from rats within 48 hours following the administration of ipecac syrup containing tritium (3H)--labeled cephaeline or emetine. Metabolites were separated and quantified by thin layer chromatography (TLC) or high-performance liquid chromatography (HPLC). Biliary and urinary excretion rates of 3H-cephaeline were 57.5% and 16.5% of the dose, respectively. Cephaeline-6'-O-glucuronide was comprised 79.5% of biliary radioactivity and 84.3% of urinary radioactivity. Unchanged cephaeline was detected in 42.4% of the dose in feces. Biliary excretion rate of 3H-emetine was 6.9% of the dose. Emetine, cephaeline and 9-0-demethylemetine comprised 5.8%, 43.2% and 13.6% in hydrolyzed bile, respectively. There were no emetine-derived metabolites in urine or feces. The occurrence of unchanged emetine was 6.8% and 19.7% of the dose in urine and feces, respectively.

Emetine, Ipecac, Ipecac Alkaloids and Analogues as Potential Antiviral Agents for Coronaviruses

“…Intramuscular administration of emetine has a number of advantages over oral dosing. Emetine undergoes metabolism by the liver [15]. Intramuscular administration would prevent any liver metabolism during oral absorption (the "first-pass effect").…”

Alkaloids from Marrubium vulgare L.: Antioxidant and Anti-Inflammatory Activities as a Function of Extraction Methods

“…In fact, the two studied compounds are quite similar, and Emetine can demethylated to get converted to Cephaeline. 51 Additionally, both alkaloids dispose of a topological polar surface area (TPSA) ranging from 20 Å to 130 Å as indicated by SwissADME software analysis. This confirms our approximation in section II, as these alkaloids are considered average polarity compounds.…”

Low dose of emetine as potential anti-SARS-CoV-2 virus therapy: preclinical in vitro inhibition and in vivo pharmacokinetic evidences

“…In order to obtain an envision for the clinical translation, we then tried to examine the pharmacokinetic (PK) profiles of Emetine in the preclinical in vivo models. Although there has been some random PK studies either with Emetine itself or Ipecac syrup (containing Emetine) [15,16], in order to obtain the detailed PK spectrum, we first systematically investigated Emetine in different species including mice, rats and beagle dogs to depict an overall picture ( Table 1). The results showed that in mice and rats, oral administration of Emetine reached maximum concentration (C max ) in the blood plasma in a relatively long time (T max : 1.67 h and 9 h for the mice and rats respectively).…”