Palatability of tablets and capsule forms of N-acetylcysteine and methionine and associated adverse events in healthy volunteers

Abstract

Objective: To evaluate the palatability and adverse events associ ated with tablets and capsule forms of N-acetylcysteine (NAC) and methionine in healthy volunteers to guide the provision of cost-effective antidotes. Methods: Forty healthy students were enrolled in this single blind randomized control study. Each volunteer was randomly assigned to receive therapeutic doses of NAC (70 mg/kg) in capsules (NAC_cap), NAC tablets (NAC_tab), methionine (2500 mg) capsules (Meth_cap), methionine tablets (Meth_tab) and folic acid as a control over five weeks. Volunteers were kept isolated in 5 rooms of a tertiary care hospital and were asked to rate the taste, smell, ability to swallow, after taste and over all acceptability in a Visual Analog Scale (VAS) from 0 to 5 (100 mm) and any adverse events that occurred within 1 hour. VAS scores were analyzed by Friedman's non-parametric and Wilcoxon sign rank tests. Results: Forty students were enrolled but only 33 (9 females and 24 males) completed all 5 dosage forms. Median age was 23 (IQR 23–22) years. Palatability ratings (Table 1) for taste, smell and “ease to swallow” were similar (Friedman’s 4.7, p ¼ .19, Friedman’s 2.6, p ¼ 0.46, Friedman’s 6.5, p ¼ .09). However, there were significant differences in after taste (Friedman’s 9.8, p ¼ .02) and overall acceptability (Friedman’s 10.2, p ¼ .02). The rank order of overall acceptability was NAC_cap, NAC_tab, Meth_tab and Meth_cap with statistically significant differences (p < .01) between Meth_cap and Meth_tab, NAC_cap and Meth_cap, NAC_tab and Meth_cap. NAC_cap had a more acceptable after taste than Meth_cap (p ¼ .001). There were no reported adverse events with Meth_tab. Five reported mild nausea and two abdominal dis comfort with Meth_cap. Mild nausea was also reported with NAC_cap (n ¼ 2) and NAC_tab (n ¼ 2). Conclusion: NAC capsules were the preferred preparation, but all were palatable and tolerated sufficiently well to be used in resource poor settings. Nausea was infrequent with any preparation.