Evaluation of Single‐ and Multiple‐Dose Pharmacokinetics of Synthetic Conjugated Estrogens, A (Cenestin®) Tablets: A Slow‐Release Estrogen Replacement Product

Abstract

A multiple-dose, placebo-controlled, randomized pharmacokinetic study was performed in 15 early (i.e., 1-3 years) postmenopausal women to evaluate the single and steady-state pharmacokinetics of 0.625 mg Cenestin (Synthetic Conjugated Estrogens, A) tablets, administered once daily for 90 days. Plasma concentration-time profiles for both total (conjugated and unconjugated) estrone and equilin, two major estrogens in Cenestin, were nearly superimposable between Day 1 (single dose) and Day 90 (multiple dose), indicating equivalent drug exposure from one dose to the next. For total estrone, the mean estimates of Cmax and AUC0-24 were 2.5 ng/ml and 35.0 ng x h/ml for Day 1 and 3.0 ng/ml and 39.8 ng x h/ml for Day 90, respectively. Similarly, Cmax and AUC0-24 mean values for total equilin were 1.4 ng/ml and 17.4 ng x h/ml after Day 1 and 1.5 ng/ml and 17.3 ng x h/ml after Day 90, respectively. The mean tmax value for total estrone was 8.3 hours on Day 1 and 8.6 hours on Day 90, indicating a slower rate of absorption. The average estimate for observed drug accumulation index for the 24-hour dosing interval was calculated to be 1.1 for total estrone and 1.0 for total equilin. These data, taken together, indicate a slow and steady rate of absorption, minimal drug accumulation at steady state, and consistent drug exposure between Cenestin doses.

Review of the effects of 17α‐estradiol in humans: a less feminizing estrogen with neuroprotective potential

“…These values are summarized in Table 2. Again for comparison, note that the plasma C max from the highest dose (0.2 mg/ subject) in the Dykens et al [2005a] Phase I clinical study of the sodium salt of 17a-estradiol 3-sulfate was 619 pg/ml, and that postmenopausal women dosed with 0.625 mg Cenestin s (a branded blend of synthetic conjugated estrogens) achieve total estrone C max levels of 2,500-3,000 pg/ml [Stevens et al, 2002].…”