Comparative Safety, Bioavailability and Pharmacokinetics of Oral Dexamethasone, 4mg and 20 mg Tablets, in Healthy Volunteers Under Fasting and Fed Conditions: A Randomized Open-Label, 3-Way Crossover Study.

Abstract Background Glucocorticoids, particularly dexamethasone, is often used in combination with novel agents in multiple myeloma. This study compared the safety, rate and extent of absorption of a single dose of an orally administered 20mg dexamethasone tablet to five 4mg tablets (total 20mg). Methods A single-center, open-label, randomized, three-way crossover comparative study. Thirty-six volunteers received at least one dose of either a single 20mg dexamethasone tablet, under fasting or fed conditions, or five 4mg dexamethasone tablets (total 20mg). Blood samples were collected before study drug administration and at 21 time points for up to 36 hours after drug administration. Results Mean AUC0–t, AUC0–∞ and Cmax were 1314.38ng • h/ml, 1329.24ng • h/ml and 257.22ng/ml, respectively for fasting test formulation (single dexamethasone 20mg tablet), 1339.74ng • h/ml, 1358.07ng • h/ml and 194.56ng/ml, respectively for the fed test formulation (single dexamethasone 20mg tablet), and 1325.12ng • h/ml, 1342.12ng • h/ml and 244.12ng/ml, respectively, for the reference formulation (five dexamethasone 4mg tablets). The median Tmax was 0.997h for the fasting and 2.502h for the fed test formulation, compared to 1.495h for the reference. Mean plasma elimination half-lives (t1/2) were 4.0h (test fasting), 4.03h (test fed), and 3.96h (reference). The point estimates and 90% confidence intervals (CI) for AUC0–t, AUC0–∞ and Cmax were 99.37% (95.65–103.24%), 99.24% (95.47–103.16%) and 106.28% (97.69–115.62%), respectively, satisfying the bioequivalence criteria of the USFDA guidelines. Conclusion The two formulations were well tolerated and one 20mg tablet or five 4mg tablets of dexamethasone are bioequivalent under fasting conditions and thus may be prescribed interchangeably.