Bioequivalence Study of Two Minocycline Capsule Formulations in Healthy Volunteers

Abstract

The bioequivalence of two capsule formulations containing 100 mg minocycline was assessed in 12 healthy adult male and female volunteers in a crossover, randomized, single-blind study. The participating volunteers were required to fast overnight and in the next morning and were given orally one capsule of the test drug (Acnez) or one capsule of the reference drug. Blood samples were drawn immediately before taking the drug (control), and at 0.33, 0.67, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, and 60 h after drug administration. One week after the first drug administration (washout period), the procedure was repeated using the alternate drug. Plasma concentrations of the drug were determined by high performance liquid chromatography method with ultraviolet detection (HPLC-UV). The pharmacokinetic parameters assessed in this study were area under the plasma concentration-time curve from time zero to 60 h (AUC(t)), area under the plasma concentration-time curve from time zero to infinity (AUC(inf)), the peak plasma concentration of the drug (C(max)), time needed to achieve the peak plasma concentration (t(max)), and the elimination half life (t1/2). The mean AUC(t), AUC(inf), C(max), and t were 18038.55 ng x h x mL(-1), 19648.21 ng x h x mL(-1), 1076.01 ng x mL(-1), and 17.33 h, respectively, for the test drug and 17979.43 ng x h x mL(-1), 19639.78 ng x h x mL(-1), 1095.97 ng x mL(-1), and 16.44 h, respectively, for the reference drug. The median (range) of t(max) of the test drug and reference drug were 2.0 (1.0-4.0) h and 2.0 (0.67-4.0) h, respectively. The geometric mean ratios of the test drug/the reference drug for AUC(t), AUC(inf), and C(max) were 98.27% 98.30%, and 97.31%, respectively. The 90% confidence intervals (CIs) were 89.26-108.19% for AUC(t), 89.95-107.41% for AUC(inf), and 89.55-105.73% for C(max). Using Wilcoxon matched-pairs test on the original data, there was no statistically significant difference found between the test and the reference drug products for t(max), values. It can be concluded that the two minocycline capsules (test drug and reference drug) are bioequivalent in terms of the rate and extent of absorption.

Randomized, Open-Label Study of the Pharmacokinetics and Safety of Oral and Intravenous Administration of Omadacycline to Healthy Subjects

“…Both doxycycline and minocycline, which are well absorbed after oral administration, have a half-life of approximately 16 h and a T max of about 2 h (10–12). Some newer tetracycline-derived compounds have even longer half-lives but may have lower oral absorption and bioavailability (10, 13).…”

Minocycline reduces mechanical allodynia and depressive-like behaviour in type-1 diabetes mellitus in the rat

“…Interestingly, administration of minocycline, an FDA-approved second-generation semisynthetic derivate of tetracycline [24,25], selectively inhibited microglia activation to the classical proinflammatory state (M1), but not the activation to the alternative anti-inflammatory state (M2), which is believed to promote neuroprotection and regeneration after injury [26]. As a result, minocycline treatment attenuated hypersensitivity in several models of neuropathic pain (e.g., [27][28][29]), including PDN [15,[30][31][32].…”

Minocycline, a putative neuroprotectant, co-administered with doxorubicin-cyclophosphamide chemotherapy in a xenograft model of triple-negative breast cancer

“…In MDA-MB-468 cells, however, a statistically significant increase in cell viability was observed at the highest concentrations tested (75 and 100μM; t-test, p<0.05, vs 0μM). The clinical relevance of the effects of these minocycline concentrations, however, is questionable as they are at least an order-of-magnitude greater than the plasma C max achieved with various clinical oral formulations of minocycline (Agwuh and MacGowan, 2006; Araujo et al, 2001; Setiawati et al, 2009; Abramowicz, 2006; Gupta et al, 2006). …”