The pharmacokinetics of amygdalin

Abstract

Amygdalin (D-mandelonitrile-beta-D-gentiobioside) is a cyanogenic glycoside claimed to show anti-cancer activity, sold under the incorrect name "Laetrile". For a sensible discussion of its alleged activity and its established toxicity it is necessary that its fate in the organism is known. The pharmacokinetics of amygdalin have been investigated in the Beagle dog after both intravenous and oral administration. The excretion of amygdalin has also been studied in the rat. Amygdalin concentrations were determined by high performance liquid chromatography in plasma ultrafiltrate and urine. The pharmacokinetics of amygdalin after intravenous administration were compared with those of diatrizoate, a model substance for extracellular volume and glomerular filtration. The amygdalin clearance is significantly larger than that of diatrizoate. The volumes of distribution of both substance are the same. After oral administration only a few percents of the amygdalin dose are systemically available. A part of the oral dose is recovered from the urine as prunasin (D-mandelonitrile-beta-D-glucoside).

Simultaneous determination of six hydrophilic components in rat plasma after oral administration of Jitai tablet by liquid chromatography–electrospray ionization–tandem mass spectrometry: Application to a pharmacokinetic study

“…Various analytical methods based on liquid chromatography technology have been developed for the determination of the six compounds in biological fluids, respectively [18][19][20][21][22][23][24]. However, these methods have shortens: high limit of quantification, long analysis time, or could not fulfill oral PK study due to the insufficient sensitivity and specificity.…”

Opinion of the Scientific Panel on contaminants in the food chain [CONTAM] related to cyanogenic compounds as undesirable substances in animal feed

“…Thus, although cyanogenic glycosides may undergo acid hydrolysis (Eyjolfsson, 1970;Bradbury et al, 1991), the conditions in the mammalian stomach, together with the relatively short passage time, will allow the main fraction to pass to the intestine. Once in the intestine of a non-ruminant, the glycosides are absorbed, as has been demonstrated for linamarin in a number of animal species and in humans (Barrett et al, 1977;Philbrick et al, 1977, Brimer andRosling, 1993;Hernandez et al, 1995), and for prunasin (prulaurasin) and amygdalin in different animal species (Carter et al, 1980;Rauws et al, 1982Rauws et al, , 1983Sakata et al, 1987). Alternatively they will be hydrolysed by micro-organisms (Carter et al, 1980;Bourdoux et al, 1982;Poulton, 1993).…”

“…As already described in Chapter 6, all cyanogenic glycosides investigated so far can be absorbed into the blood stream (Barrett et al, 1977;Philbrick et al, 1977, Brimer andRosling, 1993;Hernandez et al, 1995;Carter et al, 1980;Rauws et al, 1982Rauws et al, , 1983Sakata et al, 1987). However, all evidence available indicates that the absorbed glycosides (no matter the structure of the aglycone or the sugar part) are excreted unchanged in the urine of the organism (Ames et al, 1978;Moertel et al, 1981, Brimer andRosling, 1993;Hernandez et al, 1995).…”

“…The volume of distribution and clearance for amygdalin were found to be 0.19 L/kg and 0.39 L/kg respectively, while the corresponding figures for prunasin were 0.34 L/kg and 0.55 L/kg. For both compounds a two-compartment model was found to fit the kinetics measured after intravenous administration (Rauws et al, 1982(Rauws et al, , 1983.…”

Kobaylarda amigdalinin elektrokardiyogram ve kan nitrik oksit düzeyine etkisi

“…Amigdalin hayvansal dokularda, gastrointestinal sistemdeki kadar etkin bir hidrolize uğratılamadığından (1) parenteral uygulamalarda daha etkin sonuç alabilmek için çok daha yüksek dozlarda kullanılması gerekmektedir (35). Bu nedenle, ilacın ağız yoluyla uygulanması tercih edilmiştir.…”