PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Administration, Intravaginal”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 127 records · Page 7Linked to original sources

Serum levels of oestrogens, progesterone, follicle-stimulating hormone and sex-hormone-binding globulin during simultaneous vaginal administration of 17 beta-oestradiol and progesterone in the pre- and post-menopause.

Serum concentrations of 17 beta-oestradiol (E2), unconjugated oestrone (E1), total oestrone (tE1), progesterone (P), follicle-stimulating hormone (FSH) and sex-hormone-binding globulin (SHBG) were measured before and after daily intravaginal administration of 250 micrograms micronized E2 and 10 mg micronized P for 14 days to 12 post-menopausal and for 1 day only (during cycle days 5-8) to 11 pre-menopausal women. In the post-menopausal women the levels of all steroids increased to maximum values on day 1, 8-10 h after administration and fell thereafter. In the pre-menopausal women the steroid concentrations rose slowly to a plateau level 10-15 h after administration. Significantly higher absorption of E2 and E1 (area under the curve increments) was noted in the post-menopausal than in the pre-menopausal women. In the post-menopausal women the steroid levels measured on days 7 and 14 corresponded to those observed in the very early or late luteal phase. Area under the curve increments were usually smaller on days 7 and 14 than on day 1 and the absorption kinetics altered to a 'pre-menopausal' pattern. FSH levels were significantly reduced as from 12 h after administration on day 1 and onwards. A slight (10%) but significant increase in SHBG levels was noted on day 14. It was concluded that the combined E2 and P treatment used in this investigation brings about a physiological response with only minimal side effects on the liver as judged from changes in SHBG concentrations.

Administration, Intravaginal↗

Does intravaginal probiotic supplementation increase the pregnancy rate in IVF-embryo transfer cycles?

This study investigated the effect of intravaginal administration of probiotics immediately after oocyte retrieval on vaginal colonization and outcome of the IVF-embryo transfer cycle. One hundred and seventeen women who underwent ovarian stimulation and IVF were randomized immediately after oocyte retrieval into two groups: those who received intravaginal probiotics (study group, n = 50) and those who did not (control group, n = 67). Vaginal colonization with lactobacilli and pregnancy rate were compared between the two groups. No significant between-group differences were observed in patient age, oestrogen and progesterone concentrations on day of human chorionic gonadotrophin administration, number of oocytes retrieved, fertilization rate, number of embryos transferred, or pregnancy rate. The presence of lactobacilli in the vagina during oocyte retrieval or embryo transfer did not improve the pregnancy rate. Furthermore, intravaginal administration of lactobacilli following oocyte retrieval did not affect the prevalence of lactobacilli during embryo transfer, or the pregnancy rate. Intravaginal probiotic supplementation immediately after oocyte retrieval has no effect on vaginal colonization or pregnancy rate in IVF cycles.

Administration, Topical↗

Intravaginal toxicity studies of a gel-microemulsion formulation of spermicidal vanadocenes in rabbits.

Bis-cyclopentadienyl complexes of vanadium(IV) or vanadocenes are rapid and potent inhibitors of human sperm motility with potential as a new class of contraceptive agents. We investigated the toxicity potential of intravaginally administered gel-microemulsion formulation of two representative vanadocenes, vanadocene acetylacetonato monotriflate (VDACAC) and vanadocene dithiocarbamate (VDDTC), in the rabbit model. New Zealand White rabbits in subgroups of three were exposed intravaginally to a gel-microemulsion with and without 0.1 or 0.25% VDACAC and VDDTC for 10 consecutive days. The doses of vanadocenes used were nearly 500- to 1250-fold and 2000- to 5000-fold higher than their respective in vitro spermicidal EC50 values. Animals were euthanized on day 11 and vaginal tissues were evaluated for local toxicity by histopathology, cell proliferating activity by immunohistochemical detection of proliferating cell nuclear antigen (PCNA), and in situ apoptosis by the terminal deoxynucleotidyl transferase-mediated FITC-deoxyuridine triphosphate nick end-labeling (TUNEL) assay and confocal laser scanning microscopy (CLSM). Blood was analyzed for clinical chemistry profiles. Vanadium content in selected organs and body fluids was determined by atomic absorption spectroscopy. None of the rabbits given 0.1% VDACAC and VDDTC intravaginally developed epithelial ulceration, edema, leukocyte influx, or vascular congestion characteristic of inflammation. Only minimal to moderate irritation was observed at 0.25% VDACAC and VDDTC. A significant decrease in epithelial and stromal PCNA expression was observed in the 0.25% dose group. However, TUNEL assay and CLSM revealed no staining in the vaginal epithelium and only minimal nonspecific staining in the stroma. Repetitive intravaginal application of 0.1 or 0.25% VDACAC and VDDTC had no adverse effects on clinical chemistry profiles. Vanadium was not incorporated into rabbit tissues and body fluids at levels above 1 microg/g. Thus, intravaginal administration of VDACAC and VDDTC at concentrations nearly 500 and 2000 times higher than their respective in vitro spermicidal EC50 values did not induce marked vaginal irritation, mucosal toxicity, or systemic absorption of vanadium in the rabbit model. The lack of significant mucosal or systemic toxicity of intravaginal vanadocenes observed may have particular clinical utility as a new class of contraceptive agents.

Administration, Intravaginal↗

Vaginal contraceptive activity of a chelated vanadocene.

Bis(cyclopentadienyl) complexes of vanadium (IV) or vanadocenes are rapid and potent inhibitors of human sperm motility with potential as a new class of contraceptive agents. This study sought to determine the vaginal contraceptive activity of vanadocene dithiocarbamate (VDDTC), a stable vanadocene (IV)-chelated complex, using the standard rabbit model as well as the domestic pig as a physiologically relevant animal model for contraception. In experiment I, ovulating New Zealand White does in subgroups of eight were artificially inseminated (AI) with semen mixed with VDDTC (0.01-1 mM) or vehicle. In experiment II, ovulating does in subgroups of 18 were AI at 5 and 60 min after intravaginal application of a gel with and without 0.1% VDDTC or 2% nonoxynol-9 (N-9) (Gynol II, Ortho Pharmaceutical, Raritan, NJ), and allowed to complete term pregnancy. In experiment III, seven sexually mature Duroc gilts in standing estrus were AI with and without intravaginal application of 0.1% VDDTC gel microemulsion. Exposure of rabbit semen to VDDTC at the time of artificial insemination resulted in a dose-dependent reduction in fertility. Exposure of semen to 1 mM VDDTC led to complete inhibition of fertility as assessed by the number of embryos (control 49/94 vs. VDDTC-treated 0/117, p<.0001) or the percent embryos (52% vs. 0%, respectively) based on number of embryos to corpora lutea. Intravaginal administration of 0.1% VDDTC gel microemulsion or Gynol II prior to artificial insemination significantly inhibited term pregnancy rates (88% and 62% inhibition, respectively) when compared to control gel alone. Vanadocene dithiocarbamate gel microemulsion provided 80% inhibition of fertility even when insemination was delayed until 60 min after intravaginal application of VDDTC gel microemulsion. Rabbits that delivered litters despite intravaginal exposure of semen to VDDTC via gel microemulsion had healthy offsprings with no apparent perinatal repercussions. In domestic pigs, intravaginal applications of 0.1% VDDTC gel microemulsion prior to artificial insemination led to complete inhibition of fertility as assessed by the number of embryos (control 29/52 vs. VDDTC-treated 0/44, p<.0001) or the percent embryos (56% vs. 0%, respectively) based on the number of embryos to corpora lutea. These results suggest that VDDTC is a potent contraceptive agent in vivo. Intravaginal use of VDDTC via a gel microemulsion has clinical potential as a safe alternative to currently used detergent-type contraceptives.

Administration, Intravaginal↗

A comparison of intravaginal misoprostol with prostaglandin E2 for termination of second-trimester pregnancy.

BACKGROUND: The most widely used medical method of terminating second-trimester pregnancy is the intravaginal administration of prostaglandin E2 (dinoprostone [PGE2]). This treatment is highly effective but is associated with severe gastrointestinal side effects and hyperpyrexia. METHODS: We conducted a prospective, randomized trial comparing the efficacy and safety of misoprostol, a prostaglandin E1 analogue (200 micrograms intravaginally every 12 hours), with the efficacy and safety of PGE2 (20 mg intravaginally every 3 hours). The study population included 55 pregnant women between 12 and 22 weeks' gestation who were undergoing termination of pregnancy for either intrauterine fetal death (37 women) or medical or genetic reasons (18 women). RESULTS: The rate of successful abortions within 24 hours was 81 percent (22 of 27 women) with PGE2 and 89 percent (25 of 28 women) with misoprostol (P = 0.47). All the women who received misoprostol had successful abortions within 38 hours. Among those who had an abortion within 24 hours, the mean interval from treatment to abortion was similar in both groups (10.6 hours with PGE2 and 12.0 hours with misoprostol, P = 0.33). The rate of complete abortion, defined as the passage of the fetus and the placenta simultaneously, was 32 percent for PGE2 and 43 percent for misoprostol (P = 0.56). Certain side effects were more frequent in the women receiving PGE2 than in those receiving misoprostol: pyrexia (63 percent vs. 11 percent; P < 0.001), uterine pain (67 percent vs. 57 percent, P = 0.58), vomiting (33 percent vs. 4 percent, P = 0.005), and diarrhea (30 percent vs. 4 percent, P = 0.012). The average cost per treatment was $315.30 for PGE2, as compared with $0.97 for misoprostol. CONCLUSIONS: Misoprostol is at least as effective as PGE2 for the termination of second-trimester pregnancy involving either a dead or a living fetus, but it is less costly, is easier to administer, and is associated with fewer adverse effects.

Abortion, Induced↗

Enhanced mucosal and systemic immune responses following intravaginal immunization with human papillomavirus 16 L1 virus-like particle vaccine in thermosensitive mucoadhesive delivery systems.

To develop more potent and convenient mucosal human papillomavirus (HPV) vaccines, we tested the effect of thermosensitive mucoadhesive vaginal vaccine delivery systems on the local and systemic antibody responses to HPV 16 L1 virus-like particles (VLP). HPV 16 L1 VLP expressed from recombinant baculovirus-infected Sf21 insect cells were delivered in phosphate-buffered saline (PBS) or thermosensitive mucoadhesive delivery systems, composed of poloxamers (Pol) and varying amounts of polyethylene oxide (PEO). Pol/PEO-based vaginal vaccine delivery systems existed in liquid form at room temperature, but gelled at 37 degrees C. The mucoadhesiveness of Pol/PEO-based delivery systems increased with PEO, but the formulations with PEO higher than 1.0% were too viscous to be administered into the vagina. Vaccine vehicles affected the vaginal and salivary immune responses to HPV 16 L1 VLP intravaginally administered into mice. At 42 days after the first intravaginal immunization of HPV 16 L1 VLP with cholera toxin, vaginal and salivary IgA titers were the highest in the group given in Pol/PEO 1.0% vehicle followed by Pol/PEO 0.4% and PBS vehicles. Intravaginal coadministration of HPV 16 L1 VLP and cholera toxin in Pol/PEO 1.0% showed 31- and 39-fold higher titers compared to the PBS-based HPV 16 L1 VLP groups administered by intravaginal and intramuscular routes, respectively. Following intravaginal administration, Pol/PEO 1.0%, but not Pol/PEO 0.4%, showed significantly higher HPV 16 L1 VLP-specific serum IgG titers as compared to the PBS vehicle. Our results indicate that the use of in situ-gelling vaginal vaccine delivery systems with increased mucoadhesiveness would be beneficial for more effective induction of mucosal and systemic immune responses to intravaginally administered HPV 16 L1 VLP vaccines.

Administration, Intravaginal↗

Anti-nidatory effect of vaginally administered (Ala8,13, 18)-magainin II amide in the rhesus monkey.

The hypothesis that timed application of a potent anti-microbial, anti-tumor agent like magainin peptides can inhibit blastocyst implantation was examined in the present study using the rhesus monkey as the primate model. Incidence of pregnancy, vaginal bleeding patterns, serum levels of progesterone, estrogen and monkey chorionic gonadotropin were examined following vaginal administration of (Ala8,13,18)-magainin II amide, a synthetic analogue of magainin 2, via tampon during days 20 to 26 of mated cycles. Implantation occurred in two out of three animals following administration of 0.25 mg magainin, while administration of 0.5 mg (Ala8,13,18)-magainin II amide resulted in inhibition of implantation in all females with no change in lengths of treatment cycles, and subsequent cycles. It appears from the present study that, besides being a local microbicidal agent, intravaginal administration of (Ala(8,13,18))-magainin II amide is a potential anti-implantation strategy for intercepting pregnancy.

Administration, Intravaginal↗

Pharmacokinetics of intravaginal metronidazole gel.

The pharmacokinetics of a single 500 mg oral dose of metronidazole and 5 g of 0.75% metronidazole intravaginal gel (37.5 mg metronidazole) were compared in 12 adult volunteers in a randomized crossover manner. Serial serum samples were collected over a 48-hour period and analyzed for metronidazole and hydroxymetronidazole. Metronidazole serum concentrations after intravaginal administration were only 2% of concentrations seen with the standard 500-mg oral dose. The dose-adjusted maximum serum concentration (898 +/- 121 ng/mL vs. 237 +/- 69 ng/mL) and area under the serum concentration-time curve (9362 +/- 2873 ng * hr/mL vs. 4977 +/- 2671 ng * hr/mL) were significantly greater for the oral versus intravaginal dose of metronidazole. The time to reach maximum concentration (1.4 +/- 0.6 hr vs. 8.4 +/- 2.2 hr) was significantly shorter for the oral compared with the intravaginal dose. The mean bioavailability for the intravaginal gel was 56%. Our results show that the 0.75% gel formulation may offer the advantage of fewer systemic adverse effects compared with other formulations for the treatment of bacterial vaginosis.

Absorption↗

Intravaginal glyceryl trinitrate and dinoprostone for cervical ripening and induction of labor.

OBJECTIVE: This study was undertaken to evaluate the efficacy and safety of intravaginal administration of glyceryl trinitrate plus dinoprostone versus dinoprostone, for cervical ripening and induction of labor. STUDY DESIGN: A prospective, double-blind, placebo-controlled, randomized clinical trial was conducted among 196 singleton low-risk nullipara women with term pregnancies and unfavorable cervices who were randomly assigned to receive intravaginal glyceryl trinitrate plus dinoprostone or placebo plus dinoprostone. The main outcome variables were time from application to active phase of labor and to delivery. Secondary outcomes were change in Bishop score, fetal and maternal morbidity, and incidence of cesarean deliveries. RESULTS: The interval from application of the initial dose to the beginning of active phase of labor was 868 +/- 582 and 1136 +/- 692 minutes (P = .004) and from initial dose to delivery was 1339 +/- 826 and 1620 +/- 975 minutes (P = .03) for the glyceryl trinitrate and placebo groups, respectively. There were no significant differences in Bishop score change, cesarean section rate, and in the incidence of hypersystole and hyperstimulation. The incidence of tachysystole was significantly lower in the glyceryl trinitrate group (4% vs 15%, P < or = .02). No maternal and neonatal adverse effects were noted. CONCLUSION: The association of glyceryl trinitrate with dinoprostone is more effective than dinoprostone alone for labor induction in low-risk patients at term with unfavorable cervices.

Administration, Intravaginal↗

Acute intravaginal misoprostol toxicity with fetal demise.

We report a case of an overdose with fetal demise from the intravaginal administration of misoprostol. A 25-yr-old gravid female self-administered 6000 micrograms misoprostol intravaginally and 600 micrograms orally. She rapidly developed shaking chills, abdominal and extremity cramping, emesis, and confusion. Hyperthermia and hypotension developed within 3.5 h after drug administration, with a temperature of 41.4 degrees C (106 degrees F). Ultrasound at 3.5 h after drug administration showed no fetal movement or heart motion. A nonviable fetus was delivered by emergent cesarean section. Treatment of the mother was supportive and included intravaginal decontamination and endotracheal intubation with neuroparalytic therapy to control agitation and hyperthermia. Recovery was complete within 15 h of drug administration.

Abortifacient Agents, Nonsteroidal↗

Antigen recognition in the female reproductive tract: I. Uptake of intraluminal protein tracers in the mouse vagina.

Local immunization in the vagina of several species elicits immune responses, but little is known about the uptake, processing and recognition of antigens at this site. We investigated the uptake of intravaginally administered tracers using FITC-bovine albumin, FITC-horse ferritin and FITC-horseradish peroxidase in non-pregnant and pregnant mice. Tracers were detected in cells in the vaginal epithelium and stroma at diestrus, proestrus and metestrus, but not at estrus. During pregnancy, racers were present in vaginal cells on Day 6 but not on Day 13. The distribution of tracers in the vagina was the same in all mice. They were present in vaginal epithelium in cells similar to Langerhans' cells and in the stroma in cells that resembled dendritic cells, fibroblasts or macrophages. In some non-pregnant mice, tracers were present in cells adjacent to lymphatic nodules located in the adventitia between the vagina and urethra. Tracers were seen in phagocytic cells lining the marginal and medullary sinuses of the draining lymph nodes (iliac nodes) in some non-pregnant mice at 4 h after intravaginal administration, or in small, dendritic cells in the paracortex at 17 h. To test the possibility that transfer of proteins into the vagina was due to toxic effects of the tracers, FITC-conjugated proteins were also administered into the lumen of uterine horns, and their distribution in horns, cervix and vagina was studied. In uterine horns, tracers were either absent or were located only in apical vesicles in the luminal epithelium. Tracers were present in the cervix and vagina as described above for intravaginal tracers. This result suggests that uptake of tracers in the vagina was not due to toxic effects, and that the vagina and cervix are major sites of protein uptake into the reproductive tract.

Administration, Intravaginal↗

The vagina as a route for systemic drug delivery.

Exhaustive efforts have been made toward the administration of drugs, via alternative routes, that are poorly absorbed after the oral administration. The vagina as a route of drug delivery has been known since ancient times. In recent years, the vaginal route has been rediscovered as a potential route for systemic delivery of peptides and other therapeutically important macromolecules. However, successful delivery of drugs through the vagina remains a challenge, primarily due to the poor absorption across the vaginal epithelium. The rate and extent of drug absorption after intravaginal administration may vary depending on formulation factors, vaginal physiology, age of the patient and menstrual cycle. Suppositories, creams, gels, tablets and vaginal rings are commonly used vaginal drug delivery systems. The purpose of this communication is to provide the reader with a summary of advances made in the field of vaginal drug delivery. This report, therefore, summarizes various vaginal drug delivery systems with an introduction to vaginal physiology and factors affecting drug absorption from the vaginal route.

Administration, Intravaginal↗

Treatment of intravaginal HSV-2 infection in mice: a comparison of CpG oligodeoxynucleotides and resiquimod (R-848).

The mammalian innate immune system recognizes pathogens via a series of pattern-recognition receptors such as the toll-like receptors (TLR) that interact with pathogen-associated molecular patterns (PAMPs) and lead to the rapid activation of innate immune cells. In this study, we compared the efficacy of CpG ODN (a TLR9 agonist) and resiquimod (R-848; a TLR7/8 agonist) for topical immunoprophylaxis or immunotherapy of vaginal herpes simplex virus type 2 (HSV-2) infection in mice. Efficacy against HSV infection was observed with CpG ODN but less so with R-848, even after repeated administrations. Intravaginal (IVAG) administration of CpG ODN resulted in strong local but relatively weak systemic immune activation, as determined by levels of the chemokines IP-10, MIG and I-TAC in vaginal tissue and plasma, respectively. In contrast, IVAG administration of R-848 resulted in high levels of plasma IP-10, similar to those seen after parenteral administration, but overall, weaker or shorter-lived local immune responses than obtained with CpG ODN. These findings suggest that differences in biodistribution and sites of immune activation between CpG ODN and R-848 after IVAG delivery account for differences in efficacy, and demonstrate the need for local mucosal innate activation for protection against HSV-2.

Adjuvants, Immunologic↗

[Using of Misoprostol for preinduction and induction of labor in term pregnancy].

UNLABELLED: Labour induction is frequently indicated in women with an unfavourable cervix. Oxytocin and prostaglandins are the most common drugs used for labour induction. Induction of labour with prostaglandins offers the advantage of promoting both cervical ripening and myometrial contractility. The purpose of the study was to evaluate the safety and efficacy intravaginal administration prostaglandin E1 methyl analogue, misoprostol in cervical ripening and induction of labour in term pregnancy and in women with unfavourable cervix (Bishop score < = 4). The approval for this study was given by the Board of Medical Ethics, University Medical School of Lublin in Poland. MATERIALS AND METHODS: 64 women with indication for termination of pregnancy received either misoprostol (Cytotec-Searle) vaginally (group M, n = 30) or intravenous drip infusion of oxytocin(group Ox, n = 34). We evaluated profile of the studied women (gravidity, weight, height, maternal age, gestational age), effectiveness and safety of the misoprostol and need for oxytocin administration in group M, start of induction-to-active labour interval (contractions), start of induction-to-vaginal delivery interval, hyperstimulation syndrome, delivery within 24 hours of drug application and caesarean section rate. Before starting labour induction a Bishop score was obtained. Statistical analysis was performed. Baseline and outcome variables were tested with student's t-test and c2 analysis. We needed p < 0.05 for statistical significance. RESULTS: There were no differences in the patient profiles (gravidity, weight, height, maternal age, gestational age) between groups except the score of cervical ripening. The Bishop score before induction was lower in group M. The interval between the initiation of induction to active labour was shorter in the misoprostol group (334.23 +/- 126.35 versus 610.00 +/- 352.14 minutes). The mean time between the initiation of induction to delivery was shorter in group M (707.69 +/- 341.15 +/- versus 1025.77 +/- 369.16 minutes). These differences were statistically significant. 28 (93.33%) patients in the misoprostol group delivered within 24 hours compared with 24 (70.59%) women in the oxytocin group. 8 patients in the misoprostol group and 8 patient in the oxytocin group had caesarean section. Labor induction was successful in 30 (100%) women in the misoprostol group compared with 24 (70.59%) patients in the group Ox. CONCLUSIONS: Intravaginal misoprostol is an effective, easy to use and cheap drug for the induction of labour, especially for cervical ripening in women with unfavourable cervix (Bishop score < = 4).

Administration, Intravaginal↗

Ovulation induction in rabbit does submitted to artificial insemination by adding buserelin to the seminal dose.

This study was aimed at determining if a GnRH analogue, buserelin, could be used for ovulation induction in rabbit does submitted to artificial insemination (AI) by intravaginal administration, by adding the hormone to the seminal dose. In a first experiment, 39 secondiparous experimental does (Hyplus strain PS19, Grimaud Frères, France, of about 30 weeks of age) were divided into 3 groups of 13 does each, which at the moment of AI received the following treatments, respectively: (1) control: an intramuscular injection of buserelin (0.8 microg/doe), (2) 8 microg/doe of buserelin added to the insemination dose, and (3) 16 microg/doe of buserelin added to the insemination dose. The experiment was done using 3 consecutive cycles at 42 day-intervals (n = 39). Four does from each of the 3 groups had blood taken at the fourth cycle for LH determination at 0, 60, 90, 120 and 150 min relative to AI. Kindling rates were 82% (28/34), 56% (29/36) and 85% (33/39), respectively for treatments 1, 2 and 3. In the does of groups 2 and 3, LH peaks were detected 60 min after AI, whereas in the does from group 1, the LH peak was detected 90 min after AI. Prolificacy was not different for the 3 treatments (average litter sizes ranged from 10.4 to 10.8). In a second experiment, 3 buserelin concentrations (8, 12 and 16 microg/doe) were used intravaginally and compared with the control treatment (0.8 microg/doe, via intramuscular). This experiment was done using 100 nulliparous rabbit does (Hyplus strain PS19, Grimaud Frères, France, of about 19 weeks of age) (4 groups of 25 does each) located on a commercial farm, to test if the previous results would be confirmed under field conditions. Kindling rates were no different (P < 0.05) for the 4 treatment groups [91.7% (22/24), 79.2% (19/24), 87.0% (20/23) and 87.5% (21/24) respectively for the control, 8, 12 and 16 microg of intravaginal buserelin], however, prolificacy was higher when using the maximal dose of intravaginal buserelin (11.7 vs. 9.4 for the control group). It was concluded that buserelin can be used for ovulation induction in rabbit does when included in the seminal dose, with similar AI results as those obtained when the hormone is administered intramuscularly.

Administration, Intravaginal↗

Antifertility and antiproteolytic activity of activated N-carbobenzoxy amino acid esters.

N-Carbobenzoxy L-phenylalanine, glycine, L-leucine, and L-proline derivatives, their vinyl esters, and their 1,2-dibromoethyl esters were tested for antifertility activity in mice. Intraperitoneal administration reduced the pregnancy percentage and the number of fetuses per litter. Intravaginal administration reduced the pregnancy percentage significantly, with N-carbobenzoxyglycine vinly ester, N-carbobenzoxyglycine-1,2-dibromoethyl ester, N-carbobenzoxyl-L-leucine-1,2-dibromoethyl ester, and N-carbobenzoxy-L-proline-1,2-dibromoethyl ester producing 100% inhibition at 10 mg/kg/day. Sperm enzyme hydrolysis of the nonspecific substrate azocasein was inhibited significantly by certain N-carbobenzoxy amino acid esters in vitro. Specific substrate N-benzoyl-L-arginine ethyl ester hydrolysis was also inhibited. Compounds that inhibited N-benzoyl-L-arginine ethyl ester hydrolysis also demonstrated in vivo intravaginal antifertility activity.

Acrosin↗

Cholestatic hepatitis after administration of furan derivatives.

A patient developed cholestatic hepatitis while being treated with nitrofurantoin. A second episode of jaundice followed the intravaginal administration of a mixture of furazolidone and nifuroxime. It is important to consider possible cross-sensitivity of chemically related compounds even when they are administered by different routes.

Adult↗

Some biological properties of RMI 12,936, a new synthetic antiprogestational steroid.

A new synthetic steroid, RMI 12,369, was examined for its contraceptive potential in rats and comparisons with ethinyloestradiol were also made. Marked differences in the biological effects of the compounds were found, RMI 12,936 having high antiprogestational but negligible oestrogenic activity. Administration of RMI 12,936 on Day 1 of pregnancy caused acceleration of egg transport, the initial changes being apparent within 12 hr of dosing. Termination of pregnancy was associated with a significant reduction in ovarian weight. On Day 8 of pregnancy, RMI 12,936 resulted in significant ovarian hypertrophy, apparent within 48 hr, possibly due to a luteotrophic stimulus of placental origin. Pregnancy could not be maintained by progesterone implants, indicating that utilization was inhibited. Egg transfer experiments indicated that the primary effects were probably on the maternal reproductive tract. Pregnancy was terminated after administration of RMI 12,936 ON Day 19. The compound also had antifertility activity following intravaginal administration.

Androstenols↗