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

Abstract

BackgroundGlucocorticoids, particularly dexamethasone, are 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 20-mg dexamethasone tablet to five 4-mg tablets (total, 20 mg). Patients and MethodsThis was a single-center, open-label, randomized, 3-way crossover comparative study. Thirty-six volunteers received at least 1 dose of either a single 20-mg dexamethasone tablet, under fasting or fed conditions, or five 4-mg dexamethasone tablets (total, 20 mg). Blood samples were collected before study drug administration and at 21 time points for up to 36 hours after drug administration. ResultsMean area under the concentration-time curve from time zero to the time of last non-zero concentration (AUC0–t), mean area under the concentration-time curve from time zero to infinity (extrapolated) (AUC0–∞), and maximum observed concentration (Cmax) were 1314.38 ng × h/mL, 1329.24 ng × h/mL, and 257.22 ng/mL, respectively for fasting test formulation (single dexamethasone 20-mg tablet), 1339.74 ng × h/mL, 1358.07 ng × h/mL, and 194.56 ng/mL, respectively, for the fed test formulation (single dexamethasone 20-mg tablet), and 1325.12 ng × h/mL, 1342.12 ng × h/mL, and 244.12 ng/mL, respectively, for the reference formulation (5 dexamethasone 4-mg tablets). The median time of observed Cmax was 0.997 hours for the fasting and 2.502 hours for the fed test formulation, compared with 1.495 hours for the reference. Mean plasma elimination half-lives (t1/2) were 4.0 hours (test fasting), 4.03 hours (test fed), and 3.96 hours (reference). The point estimates and 90% confidence intervals (CIs) for AUC0-t, AUC0-∞, and Cmax were 99.37% (90% CI, 95.65%-103.24%), 99.24% (90% CI, 95.47%-103.16%), and 106.28% (90% CI, 97.69%-115.62%), respectively, satisfying the bioequivalence criteria of the United States Food and Drug Administration guidelines. ConclusionThe 2 formulations were well-tolerated, and one 20-mg tablet or five 4-mg tablets of dexamethasone are bioequivalent under fasting conditions and thus may be prescribed interchangeably.