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Effects of 5-hydroxytryptamine on fertility and luteal development following intravaginal administration in the rat.

Intravaginal administration of 5HT was effective in terminating pregnancy when given after implantation in the rat, provided that the tampon was allowed to remain in the vagina for 4 hr or more. Complete antifertility efficacy was associated with a prevention or reversal of the increase in ovarian weight, which occurs in untreated rats between Days 12 and 17 of pregnancy, and correlates with enlargement of the CL. Data from hysterectomized, ovariectomized and progesterone-implanted rats indicated that the effect on CL was not a cause of the antifertility effect. Intravaginal administration of 5HT was found to lead to general systemic effects.

Animals

Intravaginal administration of RU 486 in humans and rats: inadequate absorption in humans.

Vaginal absorption of the antiprogesterone steroid RU 486 was studied in humans and rats. In rats, RU 486 was sufficiently absorbed to terminate early pregnancy following vaginal, oral or intramuscular administration. The quantitation of RU 486 in serum showed that the ratios of the areas under the concentration curves per mg administered were 1:2.8:3.4 for the vaginal, intramuscular and oral routes, respectively. Female volunteers received RU 486 vaginally in polyethylene glycol (PEG) suppositories, in tampons and in oil solution. Following vaginal (PEG-suppository) and oral administration of 100 mg of RU 486, the ratio of the areas under the serum concentration curves was 1:56, respectively. From tampons and oil, RU 486 was absorbed in a similar manner to that of the PEG-suppositories, resulting in nanomolar serum concentrations. In humans no biological effects were noted following vaginal administration of RU 486. These data suggest that vaginal release of RU 486 is not a successful route of administration in humans.

Administration, Intravaginal

[Clinical studies on intravaginal administration of CDDP for dysplasia, carcinoma in situ and microinvasive carcinoma of the uterine cervix].

We attempted CDDP (cis-diaminedichloroplatinum) intravaginal administration by directly exposing the uterine cervix to CDDP in cases of dysplasia of the uterine cervix and cervical intraepithelial and micro-invasive carcinoma. Out of 12 patients, 7 had dysplasia of the uterine cervix (dysplasia was mild in 4, of an intermediate level in 1, 4 with mild dysplasia, 1 with and advanced in 2); 3 had carcinoma in situ, and 2 had microinvasive carcinoma. For CDDP intravaginal administration, a gauze tampon containing CDDP (5mg) was inserted into the vagina. CDDP administration was repeated daily for 10 days. The total dosage of CDDP administered was 50mg (new paragraph). During this period, vaginal cytologic examination was conducted and total plasma Pt content was determined daily for all. Following the completion of CDDP administration, the uterine cervices of those with dysplasia were histologically examined. For those with carcinoma in situ and microinvasive carcinoma, simple total hysterectomy was performed after intravaginal administration of CDDP to determine its therapeutic efficacy and the Pt concentration of the tissue; 1. In the 7 cases of dysplasia, dysplastic cell degeneration was observed 1-2 days after the start of intravaginal CDDP administration and these cells disappeared in all cases after its completion. 2. Sixteen histological sections of the resected cervical specimens from the 3 cases of carcinoma in situ showed complete disappearance of cancerous cells. 3. In the 2 cases of microinvasive carcinoma, no tumor cells were detected in one case; in the other case, tumor cells persisted in part of the resected specimen.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intravaginal

[Intravaginal administration of CDDP for adenocarcinoma].

Single vaginal administration of CDDP was done in a case of adenocarcinoma when relapse in the vaginal stump followed surgery for uterine corpus carcinoma. A tumor the size of a large fingertip in the vaginal stump was completely eliminated via 15-time (75 mg) CDDP vaginal administration, suggesting that this treatment was effective against adenocarcinoma. The only side effect over the whole body was slight pain developing in the external genitalia.

Adenocarcinoma

[Intravaginal administration of CDDP in cervical cancer].

An 84-year-old woman was seen on June 19, 1989 with the chief complaint of excessive abnormal genital bleeding of 10 days' duration. The patient was diagnosed as FIGO stage IV b (positive metastasis to lung and Virchow's nodes) and was urgently admitted because of massive bleeding, which was well controlled by whole pelvic irradiation (Lineac 3,000 rad). However, subsequent 3 courses of systemic combination chemotherapy including cisplatin delivered progressing disease (PD) with the evidence of exacerbation of primary and metastatic lesions. In such an intelligible case, authors applied 5 mg of CDDP for 13 consecutive days directly into the vaginal wall and made a pharmaco-dynamic kinetic study by measuring the blood and tissue Pt concentration. Cyto- and pathological analysis of tissue specimen revealed that this topical used of low-dose consecutive CDDP was effective for local tumor control even after failure of systemic chemotherapy.

Administration, Intravaginal

[Labor induction by intravaginal administration of prostaglandin E2 tablets].

Between 1982 and 1984, at Graz University Obstetric and Gynaecological Clinic, labour was induced in 307 women (146 primiparae and 161 multiparae) by intravaginal administration of 3 mg prostaglandin (PG) E2 tablets, because birth was overdue or because labour was irregular. No risk factors were present when PG was administered: signs of deficiency or postmaturity, or twisted cord, were ruled out. The following complications were evaluated: birth rate and induction-birth interval in relation to cervical maturity and parity. The number of complications was low. It was unrelated to cervical maturity and only partially to parity. Birth was induced successfully with a single dose of 3 mg PG E2 in over 80% of the primiparae and over 90% of the multiparae. The majority of the primiparae and all the remaining multiparae were successfully delivered with a second dose; no relationship between birth rate and cervical maturity was established. Among the primiparae with a low degree of cervical maturity the child was born within 12 hours in over 50% of the cases, among primiparae with more mature cervices in almost 90%. Among the multiparae, the child was born within 12 hours in 90% of the cases regardless of the state of cervical maturity. It is concluded from these results that with appropriate monitoring of birth, intravaginal administration of PG E2 tablets is an efficient and easily managed method of inducing birth at term, involving little risk.

Administration, Intravaginal

HPLC method for pharmacokinetic studies on ciclopirox olamine in rabbits after intravenous and intravaginal administrations.

This paper reports a HPLC method to detect unchanged and glucuronide derivatives of ciclopirox olamine (a substituted 2-pyridone antimycotic) and gives pharmacokinetics in rabbits after i.v. and intravaginal administration. The HPLC method utilizes a RP 18 reverse phase column, a mobile phase of water and acetonitrile (60/40), a flux of 1 ml/min and wavelength of 304 nm. For the determination of free ciclopirox the plasma drug is methylated with dimethyl sulphate, extracted with n-exane, purified on Adsorbex CN and injected into the column. For the determination of total (free and glucuronide derivatives) ciclopirox the plasma is previously hydrolized with beta-glucuronidase before the application of the above procedure. In rabbits the drug is administered at 15 mg/kg for both routes; the t1/2 elim is 2.1 hours, the total clearance/F is 0.73 1.h-1 and the distribution volume/F is 2.2 1. Ciclopirox olamine, after intravaginal administration, shows low absorption (about 2%) and is mainly transformed into glucuronide derivatives.

Administration, Intravaginal

Midtrimester abortion induced by serial intravaginal administration of prostaglandin E2 suppositories in conjunction with a contraceptive diaphragm.

Midtrimester abortion was successfully induced in 68 of 69 patients with serial intravaginal administration of prostaglandin E2 suppositories behind a contraceptive diaphragm. The mean abortion time for the successful inductions was 13.07 hours; multiparous patients aborted somewhat faster, mean 12.72 hours, as compared to nulliparous patients, mean 14.22 hours. In 36 patients the PGE2 suppositories were placed behind an intact diaphragm and the mean abortion time was 14.89 hours. In 33 patients the PGE2 suppositories were placed behind a diaphragm modified by having an opening incised in the center, the mean time in these patients was 11.96 hours. Of the 68 successful abortions 59% of the patients aborted in 12 hours or less and 88% aborted within 24 hours. The most frequently encountered side effect was temperature elevation of 2 degrees F or higher which occurred in 68% of the patients. Temperatures returned to normal levels within 4 to 6 hours after the last adminstration of PGE2. Gastrointestinal side effects occurred in 45% of patients, but these side effects were well tolerated and did not require termination of drug administration in any of the patients. Intravaginal administration of PGE2 suppositories is a very effective abortifacient technque during the midtrimester, however the use of PGE2 in conjunction with a diaphragm did not appreciabley improve the technique although the amount of drug administered and the incidence of side effects was somewhat lower than when the PGE2 suppositories are used alone. If a diaphragm is to be used, a modified diaphragm is indicated since it simplifies the clinical management of the abortion, eases administration of the suppositories and permits a more accurate estimation of cervical changes, vaginal bleeding and abortion.

Abortion, Induced

Induction of midtrimester abortion by serial intravaginal administration of 15(S)-15-methyl-prostaglandin F2alpha (THAM) suppositories.

Midtrimester abortion was successfully induced in 13 of 22 patients by serial intravaginal administration of 15(S)-15-methyl-prostaglandin F2alpha (THAM) suppositories. Nine patients, 4 nulliparas and 5 multiparas, failed to abort after 24 hours of prostaglandin administration and a concomitant infusion of oxytocin was initiated. Seven of the nine patients aborted within 7 hours of the combined therapy and one patient on methadone maintainence aborted after 17.5 hours of combined therapy, 41.5 hours after the first dose of prostaglandin. A single patient failed to abort, despite the concomitant prostaglandin-oxytocin administration and underwent surgical evacuation. The mean abortion time for the 21 successful abortions was 22.56 hours. Nulliparous patients aborted somewhat faster, mean 21.79 hours, than multiparous patients, mean 23.80 hours, but this difference was not statistically significant. In this study, one patient aborted in less than 12 hours, and 62% of the successful cases aborted within 24 hours. The plasma levels of 15-ME-PGF2alpha were analyzed by radioimmunoassay in 10 patients. Plasma prostaglandin levels rose significantly 30 minutes after the insertion of the first suppository, but there was a wide variation in levels from patient to patient. It was observed that the 2 patients with the highest levels had the fastest abortion times and episodes of gastro-intestinal side effects appeared related to a rise in prostaglandin levels. Sixty-four percent of the patients in this study had no gastro-intestinal side effect related to prostaglandin administration.

Abortion, Induced

Mid-trimester abortion induced by intravaginal administration of prostaglandin E2 suppositories.

Mid-trimester abortion was successfully induced in 70 of 71 patients by administration of vaginal PGE2 suppositories. The one patient who failed to abort with this method was pregnant in the blind horn of a duplex uterus. The mean abortion time for the successful inductions was 11.88 hours. Multiparous patients aborted somewhat faster than nulliparous patients, but the difference was not significant. Among the 70 successful inductions 42 patients aborted in 12 hours or less and only one patient had an abortion time of more than 24 hours. The drug appeared effective throughout the stages of gestation included in this series--from 8 to 27 weeks. Eight patients were monitored throughout the abortion procedure and uterine activity was calculated and analyzed. The development of uterine activity was gradual without the sudden rise in frequency of contractions and intrauterine baseline tonus that characterized prostaglandin administered by other methods. The most frequently encountered side effect of vaginal PGE2 suppositories was a temperature elevation, which returned to normal within a few hours of the last dose of the drug. Gastrointestinal disturbances--vomiting and diarrhea--were also common, despite a low initial dose of PGE2 and premedication with antiemetic and antidiarrheal agents. These side effects were in general well tolerated by the patients and never required termination of therapy. The cardiovascular effects of PGE2 in this series could be considered minimal. In a single patient surgical intervention was required to remove the placenta. In seven patients the placenta was removed by sponge forceps and in five patients the placenta was removed manually. There was an estimated blood loss exceeding 250 ml. in 10 patients, but transfusion was not required. Although white blood cell count rose significantly during the abortion period there were no significant changes in hematocrit or platelet count. Mid-trimester abortion with intravaginal administration of PGE2 suppositories appears to offer a valid alternative to the presently available techniques, with a rapid abortion time, high success rate, and low incidence of complications.

Abortion, Induced

[Labor induction at term: amniotomy versus intravaginal administration of prostaglandin E2 tablets].

This study compares the conventional method for induction of labour, amniotomy (A) with or without oxytocin infusion, with induction by means of intravaginal prostaglandin (PG)-E2 tablets. We reviewed the records of 266 women (A group: 155 women, PG group: 111 women), who had no risk factors at the time of induction. Both methods were effective. However, induction by PGE2 tablets presented less risk and was more comfortable than early amniotomy. We conclude that A should no longer be the method of choice for the induction of labour at term; the application of intravaginal PGE2 tablets is an efficacious, easy, and low-risk alternative.

Administration, Intravaginal

[The "other induction"--experiences and consequences in 281 deliveries following intravaginal administration of PGE2 tablets].

186 patients have been included prospectively in a study, aimed at analysing the course of birth after induction with 3 mg PGE2-tablets given intravaginally. These data are compared with those gained from a retrospective analysis of 95 patients using a dose of 2 mg. The total of the births within our clinic in 1986/87 functions as controls. Although in every case there has been an urgent need for the termination of pregnancy and there have been also unfavourable cervix findings in the 3 mg group, no differences could be observed in comparison to the control group concerning duration of cervical dilatation and expulsion, as well as foetal outcome parameters. When comparing the 2 mg and 3 mg groups, a certain superiority of the 3 mg dosage could be noted, leading to the opinion, that trial dosages of less than 3 mg should be abandoned. C-section rate was lowest and spontaneous birth rate was highest in the 3 mg group as compared to the 2 mg and the control groups. Permanent CTG-monitoring was not necessary. CTG-controls after 2 and 6 hours proved to be sufficient. Uterine hyperstimulation occurred in 2.1% of cases in both groups. In every case, prompt antagonization by means of high dose betamimetic therapy could be achieved. Due to reducing maternal and foetal side effects, the maximal mobility of the mother after tablet application, as well as, for the smooth congruence of cervical ripening and labour induction, the clinical use of the 3 mg tablet is a modern alternative to the classic oxytocin induction.

Administration, Intravaginal