Pharmacokinetic, safety and tolerability studies after single and multiple oral administration of Phenethyl isothiocyanate in Nutri Jelly

Abstract

Background : Phenethyl isothiocyanate (PEITC) is a dietary phytochemical with anticancer properties. Recently, it was added to Nutri Jelly, a nutritious gel developed for cancer patients with eating and swallowing problems.

Objectives : To evaluate pharmacokinetics, safety and tolerability of isothiocyanates after single- and multiple-oral administrations of 40 mg of PEITC in Nutri Jelly in healthy volunteers.

Methods : This was an open-label, single- and multiple-dose study. Ten subjects received a single dose of 40 mg of PEITC in Nutri Jelly and continued with this dose once daily for 5 days. Serial plasma samples at various times after the administration on day 1 and 5 were collected to determine total isothiocyanate levels using HPLC-based cyclocondensation assay. Single- and multiple-dose pharmacokinetics were analyzed using noncompartmental analysis. Safety and tolerability assessments included physical examination, electrocardiogram, clinical laboratory tests and adverse events.

Results : After single administration, maximum concentrations of isothiocyanates were observed at 2.65 ± 0.89 h (mean ± SD).The mean apparent volume of distribution and oral clearance were 1.13 ± 0.91 L/kg and 22.16 ± 4.31 L/h, respectively. Isothiocyanates were rapidly eliminated with the average terminal half-life of 1.75 ± 0.93 h. After multiple-dose administration, the mean accumulation index was 1.003 ± 0.007. There was no serious adverse event reported and no clinically significant abnormality was found in any of the clinical and biochemical parameters.

Conclusions : Nutri-PEITC Jelly was well-tolerated in healthy subjects with mild adverse events. Total isothiocyanates were rapidly eliminated with a short half-life. No significant accumulation was observed upon repeated doses for 5 days.