Steady-state pharmacokinetics of an extended-regimen oral contraceptive with continuous estrogen.

BACKGROUND: This study was conducted to evaluate the steady-state blood concentrations and potential accumulation of levonorgestrel (LNG) and ethinyl estradiol (EE) administered for up to 84 days and EE alone for 7 additional days as an extended-regimen 91-day oral contraceptive (OC). STUDY DESIGN: An open-label, single-site study was conducted in 30 healthy female volunteers. Subjects received daily doses of 0.15 mg LNG/0.03 mg EE for 84 consecutive days followed by 0.03 mg EE alone for 7 days. Pharmacokinetic (PK) monitoring was conducted on Days 1, 21, 84 and 91. RESULTS: The observed plasma concentrations of LNG after 84 days and of EE after 84 and 91 days were comparable to the steady-state concentrations observed at 21 days. Pharmacokinetic parameters over the 24-h dosing period were similar at all time points measured after achieving steady-state plasma concentrations. CONCLUSION: This study demonstrated that an extended-regimen OC providing 84 days of LNG/EE and 7 days of EE alone has a PK profile similar to a 28-day conventional OC regimen and does not result in any additional accumulation of these hormones.

A randomized, multiple-dose parallel study to compare the pharmacokinetic parameters of synthetic conjugated estrogens, A, administered as oral tablet or vaginal cream.

OBJECTIVE: A randomized, parallel-design study was conducted to determine the pharmacokinetic profile of synthetic conjugated estrogens A (SCE-A) vaginal cream (0.625 mg SCE-A/g) when administered at intervals (1 g once daily for 7 d, then twice weekly) over a 27-day period as compared with the pharmacokinetic profile of 0.3 mg SCE-A tablets administered once daily orally for 27 days. METHODS: Blood samples were collected 48 hours before initial dosing for baseline levels and at multiple occasions during the study until 48 hours after final study dosing (day 29). Maximum plasma concentration, time to maximum plasma concentration (Tmax), and area under the curve from 0 to 24 hours were calculated at days 1, 7, and 27; in addition, area under the curve from 0 to 48 hours was calculated at days 7 and 27, and area under the curve weekly (AUCweekly) values were calculated for both groups. For purposes of comparison, ratios of AUCweekly values for vaginal cream and oral tablets were analyzed. RESULTS: Compared with an oral daily dose of 0.3 mg SCE-A, the steady-state systemic exposure from vaginal cream application was considerably less, with the cream-to-oral ratio being 0.45 for baseline-adjusted (BA) unconjugated estradiol, 0.30 for BA unconjugated estrone, and 0.04 for unconjugated equilin (AUCweekly). At steady-state, the systemic blood levels of BA unconjugated estrone, BA unconjugated estradiol and unconjugated equilin were significantly lower in women who received biweekly application of 1 gm vaginal cream compared to women who took an oral daily dose of 0.3 mg SCE-A tablet. CONCLUSIONS: After intravaginal application of SCE-A vaginal cream, absorption of estrogens was lower compared with absorption after oral administration. At steady state, the systemic exposure of equilin, estradiol, and estrone was significantly lower after twice-weekly administration of 1 g SCE-A vaginal cream compared with that achieved with an oral daily dose of a 0.3 mg SCE-A tablet.

The efficacy and safety of a low-dose, 91-day, extended-regimen oral contraceptive with continuous ethinyl estradiol.

BACKGROUND: This clinical trial was conducted to demonstrate the efficacy and safety of a 91-day extended-regimen, low-dose combination oral contraceptive (OC) consisting of 84 days of ethinyl estradiol (EE) 20 mcg/levonorgestrel (LNG) 100 mcg, followed by 7 days of 10 mcg EE in place of placebo. STUDY DESIGN: A multicenter open-label, single-treatment, Phase 3 study evaluated women aged 18 through 40 years over a treatment period of up to 1 year (four 91-day extended cycles). All subjects completed daily paper diaries to monitor compliance, bleeding and additional forms of contraception used during the course of the study. RESULTS: A total of 1249 subjects completed the study. The Pearl Index was 2.74 (95% confidence interval, 1.92-3.78), based on 36 pregnancies that occurred after the onset of treatment and within 14 days after the last combination tablet in women aged 18-35 years. Among compliant-use subjects 18-35 years old, the Pearl Index was 1.73 based on 22 on-treatment pregnancies. The life table pregnancy rate for subjects 18-35 years of age was 2.39%. Cycle control and adverse events reported with this regimen were similar to those reported with other low-dose OCs. CONCLUSIONS: This study demonstrated effective prevention of pregnancy with a 20-mcg EE, 91-day extended-regimen OC. In addition, the regimen was well tolerated and incidence of adverse events were consistent with what has been reported with other low-dose OCs.

Streptococcus pneumoniae: description of the pathogen, disease epidemiology, treatment, and prevention.

Streptococcus pneumoniae causes significant morbidity and mortality. Children younger than 2 years and individuals older than 65 years experience the highest rates of pneumococcal disease. Efforts to treat pneumococcal disease have been complicated by increasing resistance to antimicrobials. Prevention efforts have included the pneumococcal polysaccharide vaccines and the pneumococcal conjugate vaccines, with use of these vaccines targeted to those at highest risk for disease. Information and background on S. pneumoniae and pneumococcal disease are provided. Vaccines targeted at this pathogen are reviewed, and the clinical trials that evaluated their safety, efficacy, and effectiveness are summarized. Also provided are recommendations for use of these vaccines.