Steady-State Bioavailability of Estradiol from Two Matrix Transdermal Delivery Systems, Alora and Climara

Buch, Akshay; Shen, Larry Z.; Kelly, Sandra C.; Sahota, Rachhpal; Brezovic, Christopher; Bixler, Carol; Powell, James H.

doi:10.1097/00042192-199805020-00009

Cited by 13 publications

(7 citation statements)

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“…Using an immediate release form, the time required to achieve steady state can be calculated based on the ratio of the dosing time interval, τ, to the biological half life, t ½ 1–4. A large number of clinical investigations to determine β‐estradiol (E 2 ) pharmacokinetic profiles of transdermal systems are based on results obtained after the consecutive application of the third or fourth patch 5–14. The recommendations resulting from these studies, however, tacitly assume that steady state conditions have been achieved without requiring validation of this factor by experimental or theoretical proof.…”

Section: Introductionmentioning

confidence: 99%

“…The matrix type technology for transdermal E 2 drug delivery (Figure 1) has been shown to yield significantly more stable E 2 plasma levels5–14 than the first generation patch of the liquid reservoir system type (Figure 1). 11,16–18 The improved pharmacokinetic profiles place even greater emphasis on the availability of information on when steady state conditions have been achieved and whether a potential problem might arise in regard to accumulation of the drug after multiple dosing over prolonged periods of time.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

17β‐Estradiol Matrixpatch Removal and Reapplication in Postmenopausal Women: Theoretical Predictions with an Oscillating Diffusion Coefficient Model

Rohr

Saeger-Lorenz

2002

Journal of Pharmaceutical Sciences

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

17β‐Estradiol Matrixpatch Removal and Reapplication in Postmenopausal Women: Theoretical Predictions with an Oscillating Diffusion Coefficient Model

Rohr

Saeger-Lorenz

2002

Journal of Pharmaceutical Sciences

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“…The t max for transdermal patches typically ranges from 24 to 70 hours. [5][6][7][8] These results provide evidence that the novel metered-dose transdermal spray delivers a clinically relevant dose of estradiol to the systemic circulation at steady state. It has been estimated that this metered transdermal spray delivers about 21 µg of estradiol with 1 spray.…”

Section: Discussionmentioning

confidence: 71%

“…For patches with a nominal delivery rate of 50 µg/d, reported increases in average serum estradiol concentrations were 32 to 42 pg/mL. [5][6][7][8] The normal elimination half-life (t 1/2 ) of orally administered estradiol is about 1 hour because of rapid hepatic metabolism. Estrogen absorbed through the skin has been shown to avoid the metabolic firstpass effect through the liver.…”

mentioning

confidence: 99%

Steady‐State Pharmacokinetics Following Application of a Novel Transdermal Estradiol Spray in Healthy Postmenopausal Women

Morton¹,

Gattermeir²,

Petersen

et al. 2009

The Journal of Clinical Pharma

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This study was designed to evaluate the steady-state pharmacokinetics (PK) of estradiol and its metabolites, estrone and estrone sulfate, following application of a novel estradiol transdermal spray to healthy postmenopausal women. Participants were randomly assigned in parallel to receive 1-, 2-, or 3-spray doses (24 participants/dose level) of a 1.7% estradiol metered-dose transdermal spray (1.53 mg/spray) once daily for 14 days. Blood was collected predose on days 1 to 14 and over 7 days after the last dose. Serum concentrations for all 3 analytes reached steady state by day 7 or 8 and were still slightly above baseline on day 21. Estradiol, estrone, and estrone sulfate serum concentrations generally increased with increasing dose. Mean estradiol and estrone maximum serum concentration (C(max)) following 1, 2, or 3 sprays for 14 days were 36 and 50, 57 and 60, and 54 and 71 pg/mL, respectively. Estradiol time when maximum concentration occurred (t(max)) was 18 to 20 hours. The area under the serum concentration-time curve over 24 hours following the last dose of study drug (AUC(0-24 h)) on day 14 for the 1-, 2-, and 3-spray groups, respectively, was 471, 736, and 742 pg.h/mL for estradiol; 886, 1208, and 1367 pg x h/mL for estrone; and 16,501, 26,515, and 27,971 pg x h/mL for estrone sulfate. The metered-dose estradiol transdermal spray delivers estradiol at therapeutic levels and produces low serum estrone concentrations.

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“…Large inter- and intra-patient differences in circulating E2 concentrations have been reported with transdermal E2, most likely due to individual differences in the rate of absorption of E2 across the skin layers and into the bloodstream 43 . Additionally, it is important to note that the transdermal application of E2 can result in mild to moderate adverse skin reactions, such as skin erythema 13 . At least a 2–10 mg dose of E2 is required to obtain a passage of ~50 μg E2 across the skin layers and into the bloodstream 65 .…”

Section: The Fate Of Exogenously Administered E2mentioning

confidence: 99%

Engineering poly(lactic-co-glycolic acid) (PLGA) micro- and nano-carriers for Controlled Delivery of 17β-Estradiol

2017

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With menopause, circulating levels of 17β-estradiol (E2) markedly decrease. E2-based hormone therapy is prescribed to alleviate symptoms associated with menopause. E2 is also recognized for its beneficial effects in the central nervous system (CNS), such as enhanced cognitive function following abrupt hormonal loss associated with ovariectomy. For women with an intact uterus, an opposing progestogen component is required to decrease the risk of developing endometrial hyperplasia. While adding an opposing progestogen attenuates these detrimental effects on the uterus, it can attenuate the beneficial effects of E2 in the CNS. Poly (lactic-co-glycolic acid) (PLGA) micro- and nano- carriers (MNCs) have been heavily investigated for their ability to enhance the therapeutic activity of hydrophobic agents following exogenous administration, including E2. Multiple PLGA MNC formulation parameters, such as composition, molecular weight, and type of solvent used, can be altered to systematically manipulate the pharmacokinetic and pharmacodynamic profiles of encapsulated agents. Thus, there is an opportunity to enhance the therapeutic activity of E2 in the CNS through controlled delivery from PLGA MNCs. The aim of this review is to consider the fate of exogenously administered E2 and discuss how PLGA MNCs and route of administration can be used as strategies for controlled E2 delivery.

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Steady-State Bioavailability of Estradiol from Two Matrix Transdermal Delivery Systems, Alora and Climara

Cited by 13 publications

References 0 publications

17β‐Estradiol Matrixpatch Removal and Reapplication in Postmenopausal Women: Theoretical Predictions with an Oscillating Diffusion Coefficient Model

17β‐Estradiol Matrixpatch Removal and Reapplication in Postmenopausal Women: Theoretical Predictions with an Oscillating Diffusion Coefficient Model

Steady‐State Pharmacokinetics Following Application of a Novel Transdermal Estradiol Spray in Healthy Postmenopausal Women

Engineering poly(lactic-co-glycolic acid) (PLGA) micro- and nano-carriers for Controlled Delivery of 17β-Estradiol

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