Strengths, weaknesses, opportunities and challenges for long acting injectable therapies: Insights for applications in HIV therapy

Chemicals with estrogenic activity are derived from many different natural and synthetic processes and products, including endogenous production (e.g., estradiol, conjugated estrogens), drugs (e.g., ethinyl estradiol, conjugated estrogens), plants used as foods (phytoestrogens such as genistein, daidzein, S-equol), and man-made chemicals (xenoestrogens such as bisphenol A). Human exposure to low doses of endogenous estrogens, estrogenic drugs, phytoestrogens, and xenoestrogens has the potential to improve health or disrupt normal endocrine activity, as well as impact the diverse systems with which estrogens interact, including the cardiovascular system, and lipid and carbohydrate metabolism. Mechanisms of action and diversity of adverse and non-adverse effects following human exposure to low doses of estrogen active chemicals (EACs, defined as chemicals which interact with an estrogen receptor [ER]) are poorly understood. This review summarizes our current understanding of the pharmacological acti...

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Pharmaco- and toxicokinetics of selected exogenous and endogenous estrogens: A review of the data and identification of knowledge gaps

Towards a Maraviroc long-acting injectable nanoformulation.

Central nervous system (CNS) injuries persist for years, and currently there are no therapeutics that can address the complex injury cascade that develops over this time-scale. 17β-estradiol (E2) has broad tropism within the CNS, targeting and inducing beneficial phenotypic changes in myriad cells following injury. To address the unmet need for vastly prolonged E2 release, we report first-generation poly(pro-E2) biomaterial scaffolds that release E2 at nanomolar concentrations over the course of 1-10 years via slow hydrolysis in vitro. As a result of their finely tuned properties, these scaffolds demonstrate the ability to promote and guide neurite extension ex vivo and protect neurons from oxidative stress in vitro. The design and testing of these materials reported herein demonstrate the first step towards next-generation implantable biomaterials with prolonged release and excellent regenerative potential.

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Vastly extended drug release from poly(pro-17β-estradiol) materials facilitates in vitro neurotrophism and neuroprotection

Pharmacokinetics, metabolism and serum concentrations of progestins used in contraception.

Comparative pharmacokinetics and pharmacodynamics after subcutaneous and intramuscular administration of medroxyprogesterone acetate (25 mg) and estradiol cypionate (5 mg).

Background: The efficacy of contraceptives is affected by its route and ease of administration. Herein, both pharmacokinetics and pharmacodynamics of the once-a-month combined injectable contraceptive medroxyprogesterone acetate (MPA) plus estradiol cypionate (E2-Cyp) were compared after intramuscular (IM) or subcutaneous (SC) injection in women of reproductive age. Study Design: Thirty women were randomly assigned to the SC (n=15) or IM (n=15) route of MPA 25 mg+E2-Cyp 5 mg administration. Serum samples were obtained daily for 7 days and then three times a week for 40 days in order to quantify E2, progesterone and MPA. In addition, three ultrasounds were performed on each subject to determine follicular development, and a daily record of the bleeding pattern and side effects was maintained. Results: A comparative analysis showed that the main pharmacokinetic (peak serum concentration, peak serum time, area under the serum concentration vs. time curve, absorption half-life and elimination half-life) and pharmacodynamic parameters, such as follicular development and ovulation, were similar in the SC vs. IM groups. Complete suppression in ovarian function was present in all women. The bleeding patterns and side effects were similar in both groups. Conclusions: The results presented herein demonstrate that the injection of 25 mg of MPA plus 5 mg of E2-Cyp has similar efficacy and safety with either the SC or IM route of administration. The SC option can be considered a viable self-administered contraceptive option that might increase women's compliance to contraceptive use.

Original research article Comparative pharmacokinetics and pharmacodynamics after subcutaneous and intramuscular administration of medroxyprogesterone acetate (25 mg) and estradiol cypionate (5 mg)

Background: Men have few effective methods for birth control The surgical method vasectomy is highly safe and effective although in Mexico represents only 24% of all contraceptive methods used Objective: To determine the characteristics complications and results of the men who requested and underwent no-scalpel vasectomy in the Instituto Nacional de Perinatologi­a Isidro Espinosa de los Reyes in Mexico Material and method: Retrospective cohort study with data of clinical records of men who underwent no-scalpel vasectomy from 2003 to 2007 Sociodemographic and clinical variables and complications reported as well as espermatobioscopy data were included Descriptive analysis was performed of different variables and chi squared test between proportions Results: A total of 596 no-scalpel vasectomies were performed The average age was 365 years and 134 of schooling 869% were married with 96 years of union Socioeconomic status was as follows: medium (25%) middle high (201%) and high (247%) The 943% of men requested the no-scalpel vasectomy because of satisfied fertility and 57% by morbidity in his couple The complications were as follows: epididymitis (22%) mild haematoma (15%) and contact dermatitis (02%) The surgical complications were significantly more frequent for the group with varicocele compared with the normal men group (p < 005) Azoospermia was achieved in 991% of men at 18 weeks after the no-scalpel vasectomy Early recanalization occurred in 05% of men There were no pregnancies Conclusions: The profile of men who requested no-scalpel vasectomy was in a great proportion healthy in the fourth decade of life with high school or greater satisfied fertility and high socioeconomic status No-scalpel vasectomy is a method of fertility planning very effective with low morbidity

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[No-scalpel vasectomy. Profile of acceptance and results].

Long-term contraception, reversible, have shown high rates of effectiveness and long-term compliance, with few contraindications. However, despite that Mexico has a variety of reversible contraception, most women still using less effective options. The resulting health benefits of contraception are important because they prevent unintended pregnancy, reduce the number of abortions and the incidence of death and disability related to pregnancy and childbirth complications. The Committee for Reproductive Health and Sexual Rights of the Mexican Federation of Colleges of Obstetrics and Gynecology (FEMECOG) conducted a literature review to evaluate the use of long-term contraception reversible as an effective and accessible tool to reduce the incidence unintended pregnancy and its consequences.

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Norma Velázquez-Ramírez

Papers

Comparative pharmacokinetics and pharmacodynamics after subcutaneous and intramuscular administration of medroxyprogesterone acetate (25 mg) and estradiol cypionate (5 mg).

Original research article Comparative pharmacokinetics and pharmacodynamics after subcutaneous and intramuscular administration of medroxyprogesterone acetate (25 mg) and estradiol cypionate (5 mg)

[No-scalpel vasectomy. Profile of acceptance and results].

[Reversible long-duration contraceptives: an efficient strategy to reduce non-planned pregnancies]