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At least 73 records · Page 4Linked to original sources
PubMed1986

The bioavailability of ethinyloestradiol and levonorgestrel in patients with an ileostomy.

The bioavailability of ethinyloestradiol and levonorgestrel has been studied in 5 young women with an ileostomy following surgery for ulcerative colitis and compared to that in 5 control subjects. Single i.v. and oral doses of both drugs were administered and the bioavailability calculated from the ratio of the two areas under the plasma concentration versus time curve for the two drugs. The mean bioavailability of ethinyloestradiol in the patients with an ileostomy was 55.4 +/- 10.9% (+/- S.D.) compared to a control value of 45.0 +/- 6.1% (p greater than or equal to 0.1). The mean bioavailability of levonorgestrel in the ileostomy patients was 85.2 +/- 13.1% compared to 104.6 +/- 22.3% in the controls (p greater than or equal to 0.1). Women who have an ileostomy following lower bowel surgery can rely on their oral contraceptive preparations being absorbed in the normal way.

Adult↗
PubMed1986

Bioequivalence of norethindrone and ethinyl estradiol for two different weight tablets with the same hormonal content.

Two tablets of differing weights, 100 mg (A) and 50 mg (B), of an oral contraceptive drug (OC) were compared with each other and to a solution (C) of the same components. The composition of the OC consisted of 1 mg of norethindrone (NET) and 0.035 mg of ethinyl estradiol (EE2). Both tablets were shown to differ from the solution, which was more rapidly absorbed, but were not significantly different from each other. Formulation means for NET and EE2, for each of the two products, were similar. Application of an interval test for the ratio of computed parameters demonstrated equivalence of the two formulations with respect to 0-24 hr area under the curve (AUC24) and total area under the curve (AUC+o+) for both NET and EE2 and with respect to concentration maximum (Cmax) for EE2. The data support the hypothesis for bioequivalence of the two formulations with respect to total absorption.

Absorption↗
PubMed1986

Pharmacokinetics of oral contraceptive steroids in Egyptian women: studies with Ovral, Nordette and Norminest.

Plasma concentration profiles and pharmacokinetic parameters have been obtained following single dose administration of three commonly used oral contraceptive steroid preparations, Ovral, Nordette and Norminest to Egyptian women. The constituents of the preparations are as follows: Ovral (50 micrograms ethinyloestradiol, EE2 and 500 micrograms levonorgestrel, LNG); Nordette (30 micrograms EE2 and 150 micrograms LNG); and Norminest (35 micrograms EE2 and 500 micrograms norethisterone, NOR). Peak plasma concentrations of EE2 ranged between 116-160 pg ml-1 for Ovral, 55-78 pg ml-1 for Norminest and 30-70 pg ml-1 for Nordette. There was no significant difference in half-life (t1/2), oral clearance (CL) or apparent volume of distribution (Vd). The relative values of the area under the plasma concentration-time curve (AUC) reflected well the different amounts of oestrogen in each preparation. There was no significant difference in t1/2, CL or Vd for LNG in the 2 preparations containing this progestogen. The mean AUC following Nordette (150 micrograms LNG) was 40% of that following Ovral (500 micrograms LNG; p less than 0.001). Comparing pharmacokinetic parameters for the same dose of LNG (Ovral) and NOR (Norminest) showed the AUC to be decreased and CL and Vd increased in the latter group. The study indicates that the kinetic profile of the OCS in healthy Egyptian women are similar to other ethnic populations.

Adult↗
PubMed1988

Assessment of a new low-dose once-a-month injectable contraceptive.

Norethisterone (NET) in combination with mestranol (ME), in a macrocrystalline aqueous suspension that provides sustained release of steroids, was assessed as a once-a-month injectable contraceptive in ten healthy women of reproductive age. The ovarian function was studied before and after the intramuscular administration of 12mg NET plus 1.2mg ME, delivered as crystals of 150 micron average size. Serial blood samples were taken throughout the injection intervals in all women to measure serum progesterone (P), estradiol (E2), and NET. The NET/ME preparation effectively inhibited ovulation in 23 out of the 25 injection intervals studied. The administration of this formulation induced in some women a small degree of follicular maturation not followed by luteal activity. The endometrial bleeding patterns after each injection showed a bleeding-free period of two to three weeks. The overall data demonstrate that the parenteral administration of a macrocrystalline steroid preparation of NET/ME can bring about a sustained release contraceptive system at a substantially lower dose than those currently employed in once-a-month injectable contraception.

Adult↗
PubMed1988

Estradiol plasma levels during long-term treatment with Norplant subdermal implants.

Estradiol-(E2) plasma levels were assessed in forty-seven women treated for one through seven years with the same set of Norplant implants. Each woman was subjected to one (n = 34), two (n = 11) or three (n = 2) sampling runs. At each sampling run, blood samples were drawn every third or fourth day during 5 or 6 consecutive weeks. Sampling runs were classified as ovulatory (n = 11), anovulatory (n = 49) or uncertain (n = 1) according to progesterone levels. Controls were Copper T users (n = 8), all classified as ovulatory. No significant differences were found for the mean E2 levels between Norplant users and Copper T users and between ovulatory and anovulatory cases. The mean of the peak E2 value found in each sampling run was significantly higher in anovulatory Norplant subjects than in the control group. The mean of the minimum E2 level observed was significantly lower in Norplant cases than in Copper T users. A single woman from the Norplant group and none from the Copper T group had all E2 values below 370 pmol/l. The inhibition of the reproductive function induced by Norplant implants is associated with a wider range of E2 circulating levels. None of the values observed at the extremes should cause serious concerns. High peaks are transitory and opposed by the antiestrogenic effect of levonorgestrel. Persistent low levels which could be associated with a hypoestrogenic state were observed in a single case.

Adult↗
PubMed1988

Alterations in the serum levels of gestodene and SHBG during 12 cycles of treatment with 30 micrograms ethinylestradiol and 75 micrograms gestodene.

The serum concentrations of gestodene have been measured radioimmunologically in 11 female volunteers on Day 1, 10, and 21 of the 1st, 3rd, 6th, and 12th cycle of treatment with an oral contraceptive containing 30 micrograms ethinylestradiol and 75 micrograms gestodene during the first 4 hours and 24 hours after intake. During the 1st cycle the maximal gestodene levels increased from 2.1 to 6.2 ng/ml on Day 1 to values between 7.5 and 22.0 ng/ml on Day 21. During the 3rd and 6th treatment cycle the levels were still higher with maxima between 10.1 and 26.3 ng/ml, while during the 12th cycle the gestodene concentrations were slightly lower. The serum levels of SHBG rose significantly during intake of the pill up to values between 210 and 240 nmol/l on Day 21 of each cycle, and were reduced to a certain degree during the pill-free interval. The SHBG concentrations correlated closely with the area under the gestodene concentration-versus-time curves (AUC) indicating a pronounced influence of serum protein binding upon the pharmacokinetics of gestodene. The gestodene levels of the individual women remained relatively constant during the 12 treatment cycles, although great interindividual differences were found. It is concluded that the relatively high serum concentrations of gestodene are not only based on the binding to SHBG, but probably also on an impeded metabolism of gestodene.

Adolescent↗
PubMed1988

Pharmacokinetic study of levonorgestrel used as a postcoital agent.

The pharmacokinetics and pharmacodynamics of levonorgestrel (LNG) were studied in six women given 0.75 mg LNG orally for seven days during the periovulatory phase of the menstrual cycle. Steady-state concentrations of LNG were reached within three days and serum LNG concentrations at various times on day 7 were generally lower than on day 1, presumably due to a reduced serum level of SHBG. On day 7 the volume of distribution was significantly increased and Co significantly decreased and both the clearance and elimination half-life were higher on day 7 than on day 1. Half-lives varied from 5.6 to 25.1 hours. The day-to-day intra-subject variations in serum LNG concentrations ranged from 23% to 80%. Serum concentrations of pituitary and ovarian hormones suggested that ovulation was not inhibited in four of the six subjects and was delayed in the remaining two. No significant changes in serum prolactin levels were observed.

Absorption↗
PubMed1988

Clearance of levonorgestrel from the circulation following removal of NORPLANT subdermal implants.

The disappearance of levonorgestrel from plasma after the removal of NORPLANT subdermal implants was studied in 12 women who had been treated from 5.5 to 78 months. The existence of one or two half-lives for the rate of disappearance was assessed. The influence of body weight, body fat and length of treatment upon levonorgestrel clearance was studied through stepwise regression analysis. It was found that the levonorgestrel decay rate after implant removal can be entirely accounted assuming one half-life of 42 +/- 16 h (mean +/- SD; range 13 to 62 h). Stepwise regression analysis showed that levonorgestrel half-life is positively correlated with body weight and not significantly correlated with the length of treatment or body fat. It is concluded that, after long-term administration of levonorgestrel via subdermal implants, the major part of the steroid is cleared from plasma within 96 h and that only trace amounts are detected in the following days.

Adult↗
PubMed1989

Bioequivalence of two oral contraceptive drugs containing norethindrone and ethinyl estradiol.

Two oral contraceptive drugs, Formulation A and Formulation B, both of similar hormonal content, were compared with each other to determine if they were bioequivalent. Both drugs contain 1 mg of norethindrone (NET) and 0.035 mg of ethinyl estradiol (EE). Application of an interval test for the ratio of the computed parameter means demonstrated equivalence for the two formulations with respect to the 0-24 hour area under the plasma level versus time curve (AUC24), the total area under the curve (AUCtot) and for the maximum plasma concentration (Cmax) for both ethinyl estradiol and norethindrone. The data support the hypothesis for bioequivalence of the two formulations with respect to total absorption.

Adult↗
PubMed1990

Ovarian function during use of a levonorgestrel-releasing IUD.

Ovarian function was studied for two complete menstrual cycles in 9 regularly menstruating women and for 8 weeks in three amenorrhoeic women who had used levonorgestrel-releasing IUDs (LNG-IUD) for more than four years. Nine patients using copper IUDs (Nova-T) were studied for two complete menstrual cycles as controls. According to progesterone levels, 15/17 cycles in women using LNG-IUDs were ovulatory, whereas only 8/17 cycles showed normal follicular growth and rupture as judged by ultrasound. In ovulatory cycles, the peak progesterone levels were lower than in the controls. The preovulatory estradiol and LH peak levels were also lower than in control subjects. SHBG levels were lower in LNG-IUD users than in copper IUD users. It is concluded that, although the dose of levonorgestrel released from the IUD is very low, it probably exerts an effect on the gonadotrophin secretion, which disturbs follicular development in many of the women studied, which in addition to the local effect on the endometrium, contributes to its high contraceptive efficacy.

Adult↗
PubMed1991

Interchangeability of low-dose oral contraceptives. Are current bioequivalent testing measures adequate to ensure therapeutic equivalency?

Current Food and Drug Administration guidelines for assessing the differences in bioavailability between generic oral contraceptives and brand-name products are inadequate to ensure therapeutic equivalence. The guidelines do not take into account those women who may have blood levels of active ingredients well outside the range of acceptability. Due to the narrow therapeutic range of steroids, these women may become pregnant or experience an increased incidence of breakthrough bleeding. Furthermore, oral contraceptive packaging is unique to each manufacturer, and any change in brands (and therefore packaging) can easily negate the sequential administration of the appropriate tablet. These are among the reasons proposed for placing oral contraceptives in the critical drug category, in which generic substitution and interchangeability of products should not be allowed.

Biological Availability↗
PubMed1991

Morphometric study of the human endometrium following continuous exposure to levonorgestrel released from vaginal rings during 90 days.

The effects of vaginal devices releasing levonorgestrel (LNG) at a constant rate of approximately 20 micrograms/24 hrs on the human endometrium were studied in a group of 69 normally menstruating women during a period of 90 days of continuous use. Peripheral blood samples were withdrawn three times weekly starting at day 10 of a pretreatment (control) cycle and then three times weekly from day 60 to 90 of the treatment period. The levels of LNG, estradiol, progesterone and sex hormone binding globulin (SHBG) were analyzed by radioimmunoassay techniques. Endometrial biopsies were obtained in the luteal phase of the pretreatment cycle and on day 84-87 of the treatment period. Increased bleeding occurred in most subjects exposed to the LNG-releasing device; the mean number of bleeding and spotting days was 26.4 +/- 8.9 S.D. which exceeded that found in their control cycle. Morphometric analyses of the endometrial biopsies using 9 quantitative indices, revealed highly significant changes in glands and stroma following the use of the LNG-releasing vaginal device. Irrespective of the circulating steroid levels, the administration of LNG significantly diminished the glandular diameter (p less than 0.001), reduced the volume density of the glands (p less than 0.001) and of the glandular epithelium (p less than 0.001). and modified the ratio glandular epithelium: glands (p less than 0.001). It is concluded that levonorgestrel released at a rate of 20 micrograms/24 hrs, induces characteristic changes in the histologic structure of the human endometrium. Although no simple correlation has been found between any of the endometrial indices and the numbers of bleeding/spotting days or bleeding days, the changes as such may represent biochemical alterations which could be predisposing factors for intermenstrual bleeding and spotting. To prove a causal relationship between morphological and biochemical changes and changes in bleeding patterns, further in-depth studies may be required.

Contraceptive Agents, Female↗
PubMed1991

Long-term effects of depot-medroxyprogesterone acetate on lipoprotein metabolism.

To assess the effects of depot-medroxyprogesterone acetate (DMPA) upon serum lipids and lipoproteins, a comparative study in chronic users and new acceptors was undertaken. Two groups of women of reproductive age were included in the study; group I (n = 8) was formed by new acceptors whereas, group II (n = 14) constituted DMPA users of more than five continuous years (7.0 + 2.1 years). Blood samples were taken on the day of injection and 15, 29, 57 and 92 days after the i.m. administration of 150 mg of DMPA for the measurement of total triglycerides (TG), cholesterol (CHOL) and phospholipids (PHL). In addition, the TG and CHOL content in the very low density (VLDL), low density (LDL) and high density (HDL) lipoprotein fractions obtained by ultracentrifugation were also determined. The results demonstrated a moderate increase in the serum total TG concentrations at the expense of the VLDL fraction in the group of chronic DMPA users. In both groups, the administration of DMPA induced a moderate, though not significant, decrease in total CHOL and HDL-chol, an effect that was noticed at the end of the treatment interval; the serum LDL-chol content remained unchanged. In addition, a decrease in the total serum phospholipids content was noticed after DMPA injection in both groups, which resembled the fluctuations observed in the luteal phase of normal ovulating women. The overall data indicate that acute and/or chronic DMPA administration at the dose currently employed for contraception does not induce major abnormalities in lipoproteins in serum.

Adult↗
PubMed1992

Interrelationship of serum levonorgestrel and sex hormone-binding globulin levels following vaginal and oral administration of combined steroid contraceptive tablets.

Ten women were treated daily with a standard dose contraceptive tablet containing 0.25 mg levonorgestrel (LNG) in combination with 0.05 mg ethinylestradiol. Five women used the tablet vaginally, while the other five used it orally. Blood samples were taken at frequent intervals on the first day of treatment and after 1 and 2 hours on treatment days 7 and 14. Serum LNG levels were measured by radioimmunoassay, and sex hormone-binding globulin (SHBG) was quantitated by charcoal assay. On day 1, peak concentrations of LNG (5.1 ng/ml) occurred within 2 hours in the oral group, whereas in the vaginal group a peak of 2.2 ng/ml was reached after 4 hours. After 24 hours, mean serum concentrations of LNG were 1.1 and 0.69 ng/ml in the oral and vaginal groups, respectively. In both groups, mean LNG concentrations increased dramatically on days 7 and 14 compared to day 1. There was no significant difference between the two groups in LNG concentrations, except after 2 hours on day 1. SHBG levels were increased after one day of treatment. By day 14 of treatment, there was a 3.5- to 4.5-fold rise in SHBG levels from pretreatment values in both groups. However, there was no significant difference in SHBG levels between the two groups throughout the study. A high correlation was found between serum levels of SHBG and LNG in both the vaginal and oral groups. The results suggest that the increase in serum LNG levels in women receiving combined contraceptive tablets either vaginally or orally is due to increased levels of SHBG. Also, the measured concentrations of LNG in the vaginal group are consistent with the previously reported clinical contraceptive efficacy of combined contraceptive tablets administered vaginally.

Contraceptives, Oral, Hormonal↗
PubMed1995

Influence of high doses of vitamin C on the bioavailability and the serum protein binding of levonorgestrel in women using a combination oral contraceptive.

The absence of an effect of high oral doses of vitamin C on the systemic availability of ethinylestradiol in women using a levonorgestrel-containing combination oral contraceptive (0.15 mg levonorgestrel and 0.03 mg ethinylestradiol) was demonstrated in a recent study. However, it is conceivable that the oral administration of gram quantities of vitamin C could also interfere with the sulfation of levonorgestrel (LNG) metabolites during phase II biotransformation, because sulfates represent a major part of the conjugated metabolites of LNG in the serum. This possible interaction was investigated in the aforementioned study, comparing Cmax and AUC(0-12h) values of LNG on the first and 15th day of two successive treatment cycles with and without co-medication of vitamin C. In addition, the serum protein binding of LNG and the concentration of the binding proteins SHBG and CBG were compared between both treatments. Corresponding parameters obtained during treatment with the oral contraceptive alone and during co-administration of vitamin C were evaluated statistically for possible differences. No effect of vitamin C was observed for any of the parameters investigated. Thus, the repeated oral administration of gram quantities of vitamin C does not impair the sulfation of hydroxylated metabolites of LNG. There was also no observable effect on the serum protein binding of LNG and the concentrations of SHBG and CBG in the serum. The results obtained in this study population (American women) for LNG are in good agreement with those obtained from a previous study in European women, who had taken a combination oral contraceptive containing the same doses of LNG and ethinylestradiol.

Ascorbic Acid↗