Evaluation of single- and multiple-dose pharmacokinetics of synthetic conjugated estrogens, A (Cenestin) tablets: a slow-release estrogen replacement product.
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.
Stevens
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Department of Clinical & Medical Affairs, Barr Research, Inc., Cincinnati, OH 45213, USA.
Roy
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Phelps
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D000328:Adult; D000368:Aged; D019540:Area Under Curve; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics; D004311:Double-Blind Method; D004857:Equilin / Q000097:blood; D004958:Estradiol / Q000097:blood; D045166:Estradiol Congeners / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D015914:Estrogen Replacement Therapy / Q000706:statistics & numerical data; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D004970:Estrone / Q000097:blood; D005260:Female; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause / Q000097:blood; D013607:Tablets
D003692:Delayed-Action Preparations; D045166:Estradiol Congeners; D004966:Estrogens, Conjugated (USP); D013607:Tablets; D004857:Equilin; D004970:Estrone; D004958:Estradiol; C509653:estrogens, conjugated synthetic A