Pharmacokinetics of the 1.5 mg levonorgestrel emergency contraceptive in women with normal, obese and extremely obese body mass index.

OBJECTIVE: To assess the pharmacokinetics (PK) of levonorgestrel after 1.5 mg oral doses (LNG-EC) in women with normal, obese and extremely obese body mass index (BMI). STUDY DESIGN: The 1.5 mg LNG dose was given to healthy, reproductive-age, ovulatory women with normal BMI (mean 22.0), obese (mean 34.4), and extremely obese (mean 46.6 kg/m2) BMI. Total serum LNG was measured over 0 to 96 h by radioimmunoassay while free and bioavailable LNG were calculated. The maximum concentration (Cmax), time to maximum concentration (Tmax), and area under the curve (AUC) of LNG were assessed. Pharmacokinetic parameters calculated included half-life (t1/2), clearance (CL) and volume of distribution (Vss). RESULTS: Ten normal-BMI, 11 obese-BMI, 5 extremely obese-BMI women were studied. After LNG-EC, mean total LNG metrics were lower in the obese and extremely obese groups compared to normal (Cmax 10.5 and 10.5 versus 16.2 ng/mL, both p<.01; AUC 208 and 197 versus 360 h × ng/mL, both p<.05). Mean bioavailable LNG Cmax was lower in obese (7.03 ng/mL, p<.05) and extremely obese (7.53 ng/ml, p=.198) compared to normal BMI (9.39 ng/mL). Mean bioavailable LNG AUC values were lower in obese and extremely obese compared to normal (131.6 and 127.5 vs 185.0 h × ng/mL, p<.05 for both). CONCLUSIONS: Obese and extremely obese women were exposed to lower total and bioavailable LNG than normal BMI women. IMPLICATIONS: Lower 'bioavailable' (free plus albumin bound) LNG AUC in obese women may play a role in the purported reduced efficacy of LNG-EC in obese users.

Centchroman: A safe reversible postcoital contraceptive with curative and prophylactic activity in many disorders.

Centchroman (INN: Ormeloxifene), a reversible post-coital/weekly oral contraceptive (half-life of about 168 hours), designed and developed at CDRI, Lucknow is the only non-steroidal oral contraceptive in clinical use in the world today. Synthesized in 1967 and completing pre-clinical and clinical studies in 1989, this drug was approved for marketing in 1991, social marketing in 1995 and NFPW in April 2016. It acts by preventing implantation of blastocyst in endometrium. It is the only contraceptive which neither suppresses ovulation nor interferes with the hypothalamic-pituitary-ovarian axis. It has high level of safety and is virtually free from side effects except for a delay in about 8% menstrual cycles which is not confined to any women/cycle. Besides contraception, this SERM is also clinically useful in the management of DUB, mastalgia and fibroadenoma and has promising therapeutic efficacy in a variety of cancers including breast cancer. Due to estrogenic activity, this drug also has anti-osteoporotic and cardioprotective activity. Thus, Centchroman is likely to show other curative and prophylactic activity in a wide range of other disorders.

Effect of arteether and pyrimethamine coadministration on the pharmacokinetic and pharmacodynamic profile of ormeloxifene.

The study was intended to investigate the effect of concomitant administration of antimalarial drug (pyrimethamine or arteether) on pharmacokinetic and post coitus contraceptive efficacy of ormeloxifene in female Sprague-Dawley rats. A serial sampling technique coupled with LC-MS/MS detection was utilized for quantification of ormeloxifene in plasma samples collected from female rats treated with ormeloxifene only and ormeloxifene with pyrimethamine or arteether. Coitus-proven female rats were utilized to investigate the effect of pyrimethamine or arteether coadministration on contraceptive efficacy of ormeloxifene by investigating the presence or absence of implantations and status of corpora lutea on day 10 post coitum. None of the sperm-positive rats treated with ormeloxifene with or without coadministration of pyrimethamine or arteether showed any sign of pregnancy, confirming that concomitant administration of antimalarial drugs (pyrimethamine or arteether) did not affect the pharmacodynamic profile of ormeloxifene. Although there was no sign of pharmacodynamic interaction, the volume of distribution of ormeloxifene increased significantly on cotreatment with pyrimethamine. However, coadministration of arteether did not affect any of the pharmacokinetic parameters of ormeloxifene. The compiled results of preliminary study in female rats support that pyrimethamine or arteether can be prescribed with ormeloxifene.

Pharmacokinetics of levonorgestrel and ulipristal acetate emergency contraception in women with normal and obese body mass index.

OBJECTIVE: This study compares the pharmacokinetics (PK) of levonorgestrel (LNG) emergency contraceptive (EC) and ulipristal acetate (UPA)-EC between normal-body mass index (BMI) and obese-BMI women. STUDY DESIGN: This prospective, randomized crossover study evaluates the PK of women after single doses of LNG-EC (1.5mg) and UPA-EC (30mg). Study procedures took place during clinical research unit admissions, where participants received a standardized meal and each study drug, in random order, during two separate 24-h admissions. Study staff collected 14 blood specimens (0, 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24 and 48h). We evaluated serum concentrations of LNG and UPA using liquid chromatography-tandem mass spectroscopy and estimated the PK parameters of both drugs using noncompartmental analysis. The main outcome of this study was a comparison of between-group differences in AUC0-24. RESULTS: Thirty-two women completed the study (16 in each group). Among normal-BMI and obese-BMI participants, the mean BMIs were 22.0 (range 18.8-24.6) and 34.3 (range 30.6-39.9), respectively. After LNG-EC, mean AUC0-24 and maximum concentration (Cmax) were 50% lower among obese-BMI women than among normal-BMI women (AUC0-24 100.8 vs. 208.5ng*h/mL, IQRobese-BMI 35.8, IQRnormal-BMI 74.2, p≤.01; Cmax 10.8 vs. 18.2ng/mL, p=.01). After UPA-EC, AUC0-24 and Cmax were similar between obese-BMI and normal-BMI women (AUC0-24 362.5 vs. 293.5ng*h/mL, IQRobese-BMI 263.2, IQRnormal-BMI 112.5, p=.15; Cmax 95.6 vs. 89.3ng/mL, p=.70). CONCLUSION: After a single dose of EC, obese-BMI women are exposed to lower concentrations of LNG and similar concentrations of UPA, when compared to normal-BMI women. IMPLICATIONS: Differences in LNG-EC PK by BMI group may underlie and account for the lower LNG-EC efficacy reported among obese-BMI women, but modest differences in UPA-EC PK by BMI group provide less support for variable efficacy. A pharmacodynamic study may be able to clarify whether these PK differences account for observed differences in LNG-EC and UPA-EC efficacy.

Safety data for levonorgestrel, ulipristal acetate and Yuzpe regimens for emergency contraception.

UNLABELLED: The World Health Organization (WHO) and the US Centers for Disease Control and Prevention (CDC) provide recommendations for use of emergency contraceptive pills (ECPs), including levonorgestrel (LNG) and combined oral contraceptives (COCs). A new ECP formulation, ulipristal acetate (UPA), is now available worldwide. To determine whether LNG, UPA or COC (Yuzpe) ECPs are safe for women with certain characteristics or medical conditions, we searched the PubMed and Cochrane databases for articles published from date of inception until May 2015 pertaining to the safety of LNG, UPA or Yuzpe ECP use. For direct evidence, we considered studies that looked at safety outcomes among women with certain medical conditions or characteristics taking ECPs compared with women not taking ECPs. For indirect evidence, we considered studies that reported pharmacokinetic (PK) data for ECP use among women with certain medical conditions or characteristics and studies that reported safety outcomes among healthy women taking ECPs. Five studies provided direct evidence; of these five studies, four examined LNG or Yuzpe use among pregnant or breastfeeding women, and one reported risk of ectopic pregnancy among women repeatedly using LNG ECPs. Poor pregnancy outcomes were rare among pregnant women who used LNG or Yuzpe ECPs during the conception cycle or early pregnancy. Breastfeeding outcomes did not differ between women exposed to LNG ECP and those unexposed, and there was no increased risk of ectopic pregnancy versus intrauterine pregnancy after repeated use of LNG ECPs compared with nonuse. Forty-five studies provided indirect evidence. One PK study demonstrated that LNG passes into breastmilk but in minimal quantities. In addition, nine studies examined pregnancy outcomes following ECP failure among healthy women, and 35 articles reported adverse events. Studies suggest that serious adverse events are rare among women taking any of these ECP formulations. IMPLICATIONS: Evidence on safety of ECPs among women with characteristics or medical conditions listed within WHO and CDC family planning guidance is limited. However, both direct and indirect evidence for our study question did not suggest any special safety concerns for the use of ECPs among women with particular medical conditions or personal characteristics, such as pregnancy, lactation or frequent ECP use.

Contraception and sexual health in obese women.

As the proportion of women with obesity increases worldwide, understanding the influence of body weight on sexual behavior, fertility, and contraceptive effectiveness is critical for health-care professionals and patients. Although many have theorized that obese women are different from normal-weight women regarding sexual health and behavior, current evidence for the most part disproves this. The exception is in adolescents where body image may play a role in riskier behavior, placing them at a greater risk of an unintended pregnancy. Given that most modern contraceptives were not originally evaluated in obese women, understanding how weight affects contraceptive pharmacokinetics and efficacy should be a focus of ongoing research. Evidence is reassuring that most modern contraceptive methods are safe and effective in obese women. This paper reviews what is known about sexual and contraceptive behavior, as well as the effectiveness and pharmacokinetics of modern contraceptives, for overweight and obese women.

Obesity and hormonal contraceptive efficacy.

Obesity is a major public health concern affecting an increasing proportion of reproductive-aged women. Avoiding unintended pregnancy is of major importance, given the increased risks associated with pregnancy, but obesity may affect the efficacy of hormonal contraceptives by altering how these drugs are absorbed, distributed, metabolized or eliminated. Limited data suggest that long-acting, reversible contraceptives maintain excellent efficacy in obese women. Some studies demonstrating altered pharmacokinetic parameters and increased failure rates with combined oral contraceptives, the contraceptive patch and emergency contraceptive pills suggest decreased efficacy of these methods. It is unclear whether bariatric surgery affects hormonal contraceptive efficacy. Obese women should be offered the full range of contraceptive options, with counseling that balances the risks and benefits of each method, including the risk of unintended pregnancy.

Ulipristal acetate: review of the efficacy and safety of a newly approved agent for emergency contraception.

BACKGROUND: Emergency contraception (EC) is used to prevent unintended pregnancies. The current gold standard for oral EC is levonorgestrel (LNG) administered as a single 1.5-mg dose or in 2 doses of 0.75 mg separated by 12 hours. LNG has shown to be effective up to 72 hours after coitus. Ulipristal acetate (UPA) is a selective progesterone receptor modulator approved for EC use in the United States in August 2010. UPA is administered as a one-time, 30-mg dose within 120 hours of intercourse. OBJECTIVE: The goal of this review was to provide a summary of the available literature on the use of UPA for EC. METHODS: PubMed, Cochrane Library, ClinicalTrials.gov, International Pharmaceutical Abstracts, EBSCO, and Iowa Drug Information Service were searched from February 2011 through September 2011 to identify relevant articles. Search terms included ulipristal acetate, CDB-2914, VA 2914, and emergency contraception. RESULTS: In an open-label study, UPA was effective in preventing pregnancy in 1241 women who presented for EC up to 120 hours (5 days) after unprotected intercourse, with an observed pregnancy rate of 2.1% (95% CI, 1.4%-3.1%) versus 5.5% (ie, the expected pregnancy rate without EC). The efficacy of UPA did not decrease significantly (P = 0.44) over time, with pregnancy rates at intervals between >48 and 72 hours at 2.3% (95% CI, 1.4%-3.8%), >72 and 96 hours at 2.1% (95% CI, 1.0%-4.1%), and >96 and 120 hours at 1.3% (95% CI, 0.1%-4.8%). In a single-blind, comparative noninferiority study of 1696 women, UPA was at least as effective as LNG when used within 72 hours for EC, with 15 pregnancies in the UPA group and 22 pregnancies in the LNG group (odds ratio = 0.68 [95% CI, 0.35-1.31]). In addition, UPA prevented significantly (P = 0.037) more pregnancies than LNG when used between 72 and 120 hours after unprotected intercourse, with 0 pregnancies in the UPA group and 3 pregnancies in the LNG group. In a meta-analysis, UPA prevented a greater percentage of pregnancies than LNG at intervals up to 24 hours (0.9% UPA vs 2.5% LNG; P = 0.035), up to 72 hours (1.4% UPA vs 2.2% LNG; P = 0.046), and up to 120 hours (1.3% UPA vs 2.2% LNG; P = 0.025). The most commonly (>10%) reported adverse events included headache, nausea, and abdominal pain. In addition, UPA delayed onset of menstruation by a mean of 2.1 to 2.8 days. CONCLUSIONS: Based on clinical trials, UPA seems to be a reasonably tolerable and effective method of EC when used within 120 hours of intercourse. UPA is at least as effective as LNG when used within the first 72 hours after unprotected intercourse. However, UPA may be more effective than LNG when used between 72 to 120 hours after unprotected intercourse, extending the window of opportunity for EC. UPA may provide a new option for women who require EC up to 5 days after unprotected intercourse.

Ulipristal acetate: a new emergency contraceptive.

Ulipristal acetate (UPA) is a newly developed emergency contraceptive currently available in the USA and Europe. It is approved as a 30 mg one-time dose taken within 120 h (5 days) of unprotected intercourse or failed contraception. This selective progesterone receptor modulator appears to be more effective than the levonorgestrel-containing emergency contraceptive, which must be taken within 72 h of unprotected intercourse. According to pharmacodynamic trials, UPA delays follicular maturation and ovulation. In addition, UPA may modulate the endometrium. Both Phase III clinical trials found that UPA does not lose efficacy within the 120-h dosing interval. Throughout all phases of clinical studies, UPA was shown to be well tolerated with only minimal adverse drug reactions, all of which are similar to competitor therapies.

Development and evaluation of matrix type transdermal patch of ethinylestradiol and medroxyprogesterone acetate for anti-implantation activity in female Wistar rats.

BACKGROUND: Medroxyprogesterone acetate (MPA), which increases high-density lipoprotein level, has not been used as a progestin in combination with estrogen in a transdermal patch to date. The aim of the research was to develop and evaluate a matrix-type transdermal drug delivery (TDD) system of a combination of ethinylestradiol (EE) and MPA for interception. STUDY DESIGN: The transdermal patch of EE and MPA was prepared using various film-forming polymers with and without n-dibutyl phthalate as plasticizer and with glycerol and sodium lauryl sulphate as penetration enhancer. All formulations were assayed using UV spectrophotometer by Vierordt's equation for EE and MPA. RESULTS: The percentage cumulative release of F6 (optimized formulation) named as 'AGARPRU' was found to be 99.94%±1.25% and 69.99%±1.02% (mean±SD) through rat skin and 92.69%±2.22% and 53.51%±2.11% (mean±SD) through cadaver skin for EE and MPA, respectively. Pharmacodynamic studies of 'AGARPRU' in female Wistar rats showed 100% anti-implantation activity. The in vivo results showed prolonged T(max) of 36 h for both EE and MPA after transdermal administration compared to oral route (2 h). Moreover, the area under the curve of EE and MPA revealed an increase in bioavailability after transdermal administration as compared to oral route. CONCLUSION: These findings suggested that TDD formulation aimed for postcoital antifertility activity has been successfully developed in female Wistar rats.

Levonorgestrel pharmacokinetics in plasma and milk of lactating women who take 1.5 mg for emergency contraception.

BACKGROUND: Progestin-only methods are among the contraceptive options available for breastfeeding women, however the doses of progestin used in emergency contraception (EC) have not been evaluated in nursing mothers. We therefore investigated the pharmacokinetics of 1.5 mg levonorgestrel (LNG) in lactating women. METHODS: Twelve healthy exclusively breastfeeding volunteers received 1.5 mg LNG. Women refrained from nursing for 72 h after dosing and fed their infants with milk frozen beforehand. Serial blood and milk samples were collected for 120 h and assayed for LNG and sex hormone binding globulin. RESULTS: LNG concentrations peaked in plasma and in milk 1-4 h and 2-4 h after dosing, respectively. Concentrations in milk (M) paralleled those in plasma (P) but were consistently lower (mean M:P ratio 0.28). Estimated infant exposure to LNG is 1.6 microg on the day of dosing (1 microg in the first 8 h), 0.3 microg on the second day and 0.2 microg on the third day. CONCLUSIONS: Nursing mothers may need EC. These results suggest that to limit infant exposure to the period of maximum LNG excretion in milk, mothers should discontinue nursing for at least 8 h, but not more than 24 h, after EC.

Pharmacokinetics of levonorgestrel 0.75 mg tablets.

This study examined plasma levonorgestrel (LNG) concentrations and pharmacokinetics following oral administration of a single LNG 0.75 mg tablet. Sixteen healthy female volunteers 19-44 years old enrolled in the study. Serial blood samples were drawn over 72 h after dosing in a fasting state. A gas chromatographic, negative ionization mass spectrometric detection analytical method was used to determine plasma LNG concentrations. The observed mean peak plasma LNG concentration was 14.1 +/- 7.9 ng/mL (range 6.7-39.0 ng/mL). The mean time of peak concentration was 1.63 +/- 0.74 h (range 1-4 h). The plasma LNG concentration versus time profiles were subjected to noncompartmental pharmacokinetic analysis for the purposes of determining half-lives, apparent oral clearances (Cl/F), apparent volumes of distribution after oral administration (V/F), and mean residence time (MRT). Half-lives calculated from the terminal decline in plasma LNG concentrations ranged from 16.2 h to 32.3 h (mean = 24.4 +/- 5.3 h). The Cl/F was 7.06 +/- 2.69 L/h, V/F was 260 +/- 129 L, and MRT was 27.8 +/- 5.2 h. LNG was well tolerated; there were no serious adverse events during the study.

Emergency contraception.

The last decade has seen a huge interest in emergency contraception (EC) because of the potential it has to reduce abortion rates. A variety of hormonal methods is available although mifepristone-arguably the best method-is only licensed in China. The intrauterine device is highly effective but its use is limited because of the technical skill required for successful insertion. The mechanism of action of both the Yuzpe regimen of EC and of levonorgestrel is poorly understood and for all methods there are serious methodological difficulties involved with calculating efficacy. Nevertheless the risks and side-effects of EC are negligible and the practicalities of prescribing it are extremely simple. Research and programmatic efforts should concentrate on improving availability if EC is to fulfil its promise as a public health intervention to reduce unwanted pregnancy.

On the mechanisms of action of short-term levonorgestrel administration in emergency contraception.

The effects of short-term administration of levonorgestrel (LNG) at different stages of the ovarian cycle on the pituitary-ovarian axis, corpus luteum function, and endometrium were investigated. Forty-five surgically sterilized women were studied during two menstrual cycles. In the second cycle, each women received two doses of 0.75 mg LNG taken 12 h apart on day 10 of the cycle (Group A), at the time of serum luteinizing hormone (LH) surge (Group B), 48 h after positive detection of urinary LH (Group C), or late follicular phase (Group D). In both cycles, transvaginal ultrasound and serum LH were performed from the detection of urinary LH until ovulation. Serum estradiol (E2) and progesterone (P(4)) were measured during the complete luteal phase. In addition, an endometrial biopsy was taken at day LH + 9. Eighty percent of participants in Group A were anovulatory, the remaining (three participants) presented significant shortness of the luteal phase with notably lower luteal P4 serum concentrations. In Groups B and C, no significant differences on either cycle length or luteal P4 and E2 serum concentrations were observed between the untreated and treated cycles. Participants in Group D had normal cycle length but significantly lower luteal P4 serum concentrations. Endometrial histology was normal in all ovulatory-treated cycles. It is suggested that interference of LNG with the mechanisms initiating the LH preovulatory surge depends on the stage of follicle development. Thus, anovulation results from disrupting the normal development and/or the hormonal activity of the growing follicle only when LNG is given preovulatory. In addition, peri- and post-ovulatory administration of LNG did not impair corpus luteum function or endometrial morphology.

The pharmacokinetics of 750 microg levonorgestrel following administration of one single dose or two doses at 12- or 24-h interval.

The administration of two tablets of 750 microg levonorgestrel at a 12- to 24-h interval has been shown to be a safe and effective means of emergency contraception, and Norlevo/Vikela (N/V) is a dedicated product for this indication. The aim of this study was to characterize the plasma pharmacokinetics of levonorgestrel following a single N/V tablet administration and following a second administration, 12 or 24 h after the first one in young, healthy, female volunteers under the same conditions as during clinical use. This was an open, observer-blind, randomized study with three parallel groups and three treatments performed in 24 white female volunteers randomized into three groups of eight participants, each receiving one of the following treatments: Group A, one tablet of 750 microg levonorgestrel at time -12 h and one tablet at time 0; Group B, one tablet of 750 microg levonorgestrel at time 0; Group C, one tablet of 750 microg levonorgestrel at time -24 h and one tablet at time 0. All treatments started between Day 2 and Day 6 of the menstrual cycle. Plasma levonorgestrel levels were measured at regular intervals from time 0 up to 36 h with a validated radioimmunoassay. The results of this study show that after either one single or two administrations of a tablet containing 750 microg levonorgestrel, levonorgestrel is rapidly absorbed. The absorption, distribution, and elimination profiles of levonorgestrel following the three different treatments were similar. It also indicates that 12 or 24 h after administration there remains a significant level of plasma levonorgestrel. In conclusion, this study reinforces clinical guidelines recommending that N/V tablets for emergency contraception be administered 12 to 24 h apart because levonorgestrel is present in plasma between the two administrations.

Pharmacokinetics and pharmacodynamics of anordrin (2 alpha, 17 alpha-diethynyl-A-nor-5 alpha-androstane-2 beta, 17 beta-diol diproprionate).

In order to determine the pharmacokinetics of anordrin a dose of 0.2 mg/kg of [3-14 C]anordrin was administered i.v. to 5 cynomolgus monkeys; the same monkeys received the same dose i.m. at a later date. An additional 3 monkeys received 1.0 mg/kg of [3-14C]anordrin i.m. After administration of the compound, the dipropionate esters of anordrin were rapidly hydrolyzed to the dihydroxy parent compound, anordiol. After i.v. administration, anordrin had a mean residence time (MRT) of 5.0 +/- 1.3 (SE) min. [14C]Anordiol formed from [14C]anordrin had an MRT of 139 +/- 27 (SE) min. The metabolic clearance rates (MCR) of anordrin and anordiol were 55 and 34 mL/min.kg, respectively. The apparent volume of distribution at steady state (Vss) for anordrin was 276 mL/kg, 7.5% of body weight of the animals; anordrol had a much larger Vss of 4460 mL/kg. The MRT of anordiol after i.m. administration of 1.0 mg/kg of [14C]anordrin was 26.3 days. An average of 44% of the dose appeared in urine regardless of the route of administration or dose. The MRT values of total radioactivity were the same when calculated from serum or urine after an i.v. dose, but after i.m. administration, values from urine were approximately 60% of that calculated from serum, indicating that products appearing in urine had a shorter MRT than products appearing primarily in feces. A separate group of monkeys was given anordrin i.m. in doses ranging from 0.1 to 0.4 mg/kg on the first day of menses. The regression of length of menstrual cycle on dose was significant (P = 0.004).(ABSTRACT TRUNCATED AT 250 WORDS)

Mifepristone. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential.

Mifepristone is a potent oral antiprogestogen which acts at the level of the receptor, having a high affinity for the progesterone receptor. Most of the clinical trials have studied its efficacy in the termination of early pregnancy when used in conjunction with a low dosage of a prostaglandin analogue. In these studies, mifepristone 100 to 600mg administered as a single dose or over 3 or 4 days, 36 to 48 hours before a prostaglandin analogue given vaginally, intramuscularly or orally, induced complete abortion in about 95% of women. Used alone, mifepristone is an effective cervical priming agent prior to termination of first trimester pregnancy by vacuum aspiration, and facilitates termination of second trimester pregnancy by prostaglandin by reducing the interval between the start of prostaglandin treatment and termination, the cumulative prostaglandin dosage, and the adverse effects associated with these drugs. Mifepristone can also be used to induce labour in cases of intrauterine fetal death. Mifepristone has been shown to be an effective postcoital contraceptive with a likely emergency role, since its repeated use modifies the menstrual cycle. Pilot studies have been performed in unresectable meningioma and metastatic breast cancer, and in Cushing's syndrome. Mifepristone is generally well tolerated, and thus is an effective, appropriate, medical alternative to surgical termination of early pregnancy. It has as yet unexplored potential as a postcoital contraceptive and in oncology.

Comparative cross-over pharmacokinetic study on two types of postcoital contraceptive tablets containing levonorgestrel.

A pharmaceutical and pharmacokinetic study was carried out on levonorgestrel tablets from two different sources (Hungarian- and Chinese-made). Both preparations contained 0.75 mg levonorgestrel and had been shown to have similar contraceptive efficacy and side effects when used for postcoital contraception. Absorption and bioavailability of the Hungarian-made tablets were greater as evidenced by higher serum concentrations of levonorgestrel, a greater area under the concentration-time curve during the first 24 hours, and a more marked suppressive effect on SHBG levels. These differences most probably reflect differences in their pharmaceutical formulation, in particular the extent of tablet dissolution and the degree of micronisation of levonorgestrel.

Agentes antiimplantaçäo / Anti-implantation agents

Anti-implantation agents ara characterized as drugs or methods that have their contraceptive effects between fertilization and the end of the impllantation period (days 13-14 post-fertilization). Such agents con be used im post-coital emergency, for repeated post-ovulatory use and/or for menstrual regulation process. Menstrual regulation can be achived by antiorigestins that block progesterone receptors and interfere with the preparation of the endometrium for implantation, by luteolysis causing decreased progesterone levels and interruption of the implantation process, by the uterotonic effects of prostaglandinas. RU 486 administered during yhe luteal phase induces vaginal bleeding ind both women and non-human primates and prevention of prgenancy might be possible by their use as a once-a-month menstrual regulator. As yet, no post-coital agent has been satisfactorily identified and other Anti-implantation agents are being considered