Abstract
Objective: Oral drug products can be categorized as either modified-release (MR) or immediate- release (IR) formulations based on pharmacokinetic characteristics. These formulation differences influence the desirable dosage range for therapeutic effectiveness. C max and T max values of an IR estrogen preparation are remarkably different from those of MR preparations. These differences for IR may result in increased adverse events and a shorter duration of effect. Of all approved estrogen replacement therapy products, only conjugated equine estrogens (CEE) and synthetic conjugated estrogens, A (SCE) are MR formulations. Methods: In vivo plasma level profiles (mean ± SD) were obtained by the following methods: 1) Estradiol tablet profile was obtained from a randomized, two-treatment, three-period, four-sequence, single-dose, crossover bioequivalence study in 40 healthy postmenopausal women and 2) CEE and SCE tablet profiles were obtained from a randomized, two-treatment, four-period, single-dose, crossover bioequivalence study in 36 healthy postmenopausal women. Results: Results are summarized in the table. Pharmacokinetic Parameters for Total Estrone ∗ ∗(Baseline corrected) Estradiol CEE SCE C max (ng/mL) 20.12 4.2 4.1 T max (hours) 2.54 7.5 7.7 Conclusions: The IR drug product demonstrated higher initial plasma levels, which may in turn increase the number and severity of adverse events experienced. Additionally, the decline in plasma levels after the initial early peak could result in a loss of duration of effect. Therefore, an MR formulation may have a more favorable clinical profile.
Published Version
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