Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Norethindrone”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 55 records · Page 3Linked to original sources
PubMed1998

Thalidomide does not alter the pharmacokinetics of ethinyl estradiol and norethindrone.

OBJECTIVE: To evaluate the effect of thalidomide on the plasma pharmacokinetics of ethinyl estradiol (INN, ethinylestradiol) and norethindrone (INN, norethisterone). METHODS: Ten women who had undergone surgical sterilization were enrolled in an open-label crossover study conducted in the Georgetown University Clinical Research Center. The pharmacokinetics of single doses of 0.07 mg ethinyl estradiol and 2 mg norethindrone were measured at baseline and after 3 weeks of 200 mg thalidomide. Compliance with the thalidomide regimen was assessed with use of Medication Event Monitoring System (MEMS) caps. RESULTS: No changes were observed in the pharmacokinetics of ethinyl estradiol or norethindrone with thalidomide therapy. The mean +/- SD area under the plasma concentration-time curve (AUC0-infinity) for ethinyl estradiol was 6580 +/- 1100 ng.h/L at baseline and 5970 +/- 1560 ng.h/L after the thalidomide regimen (paired t test, P > .05). The values for norethindrone were 103 +/- 54 micrograms.h/L and 107 +/- 58 micrograms.h/L (paired t test, P > .05). No changes were observed for other pharmacokinetic parameters assessed for either ethinyl estradiol or norethindrone. No accumulation of thalidomide was seen after 21 days of therapy: day 1 AUC0-infinity 41.1 +/- 13.9 micrograms.h/mL; day 21 AUC0-infinity 59.6 +/- 27.3 micrograms.h/mL (paired t test, P > .05). No changes were observed for other pharmacokinetic parameters assessed for thalidomide between days 1 and 21. Thalidomide was well tolerated but caused variable degrees of sedation. The average thalidomide compliance rate was 97%. CONCLUSIONS: The pharmacokinetics of thalidomide do not change with 3 weeks of daily dosing. Thalidomide does not alter the pharmacokinetics of ethinyl estradiol or norethindrone. Therefore there is no drug interaction between thalidomide and these 2 drugs. The efficacy of oral contraceptives containing ethinyl estradiol and norethindrone should not be affected by concomitant thalidomide therapy.

Adult↗
PubMed2000

Efficacy of continuous sequential transdermal estradiol and norethindrone acetate in relieving vasomotor symptoms associated with menopause.

OBJECTIVE: This study was undertaken to evaluate the efficacy and tolerability of a combination estradiol plus norethindrone acetate transdermal delivery system given in a continuous sequential regimen with transdermal estradiol versus placebo in the treatment of vasomotor symptoms of menopause. STUDY DESIGN: This was a 12-week double-blind trial of 220 healthy postmenopausal women with > or = 8 moderate to severe hot flushes and sweating episodes per day. Women were randomly assigned to wear transdermal placebo patches or a transdermal patch releasing 50 microg/d 17beta-estradiol alone (Vivelle) for days 1 to 14 of each cycle and a combination patch releasing 50 microg/d 17beta-estradiol plus 1 of 3 dosage levels (140, 250, or 400 microg/d) of norethindrone acetate (CombiPatch) for days 15 through 28. RESULTS: There was a significant (P <.001) reduction by the second week in the mean number of daily hot flushes from baseline to end point with all 3 doses of estradiol plus norethindrone acetate compared with placebo. Significant (P <.001) reductions in the mean intensity of hot flushes and sweating were also noted with estradiol plus norethindrone acetate compared with placebo. The incidences of adverse events with all 3 doses of estradiol plus norethindrone acetate and with placebo were comparable. CONCLUSION: An estradiol plus norethindrone acetate transdermal delivery system administered in a continuous sequential regimen with transdermal estradiol was well tolerated and effective for the treatment of moderate to severe vasomotor symptoms in postmenopausal women.

Administration, Cutaneous↗
PubMed2001

Minimal androgenic activity of a new oral contraceptive containing norethindrone acetate and graduated doses of ethinyl estradiol.

The pharmacokinetics and androgenic activity of Estrostep, a new oral contraceptive providing low-dose estrogen in a graduated sequence with a constant dose of progestin, were characterized in an open-label, nonrandomized study in 17 normally cycling women treated for three cycles with Estrostep. Women received 1 mg of norethindrone acetate daily combined with 20 microg of ethinyl estradiol daily for the first 5 days (1/20), 30 microg of ethinyl estradiol daily for the next 7 days (1/30), and 35 microg of ethinyl estradiol daily for 9 days (1/35). No medication was given for 7 days in each cycle to allow for withdrawal bleeding. Serial blood samples for the measurement of ethinyl estradiol and norethindrone concentrations were collected on days 5, 12, and 21 of the third treatment cycle for the 1/20, 1/30, and 1/35 dose, respectively. Sex hormone-binding globulin (SHBG) and free testosterone were measured at baseline, on day 1 of cycles 2 and 3 (SHBG only), and on days 5, 12, and 21 of cycle 3. Mean steady-state plasma ethinyl estradiol and norethindrone concentrations increased over cycle 3. The increases in ethinyl estradiol concentrations were proportional to dose. The increases in norethindrone concentrations were related to ethinyl estradiol-dependent increases in SHBG concentrations, which were 218%, 253%, and 296% of baseline values on days 5, 12, and 21, respectively. Mean plasma free testosterone concentrations decreased 47%, 60%, and 64% below baseline on days 5, 12, and 21 of cycle 3, respectively. Graduated ethinyl estradiol doses combined with a constant norethindrone acetate dose progressively increase SHBG and decrease free testosterone, which overrides any theoretic concerns of androgenic activity of norethindrone acetate. Although true androgenic activity can be determined only by assessing endpoints such as acne, hirsutism, and lipids in large controlled trials, the observed changes in circulating SHBG and free testosterone concentrations indicate that Estrostep has little, if any, intrinsic androgenic activity.

Adult↗
PubMed2003

Reduced vaginal bleeding in postmenopausal women who receive combined norethindrone acetate and low-dose ethinyl estradiol therapy versus combined conjugated equine estrogens and medroxyprogesterone acetate therapy.

OBJECTIVE: The purpose of this study was to compare the effects on vaginal bleeding patterns of continuous combined hormone replacement therapy with norethindrone acetate and ethinyl estradiol versus conjugated equine estrogens and medroxyprogesterone acetate. STUDY DESIGN: Three hundred fifty-seven postmenopausal women were selected randomly (in a blinded manner) to 12 months of treatment with 1 mg norethindrone acetate/5 microg ethinyl estradiol, placebo, or open-label 0.625 mg conjugated equine estrogens/2.5 mg medroxyprogesterone acetate (conjugated equine estrogens/medroxyprogesterone acetate [CEE/MPA]; Prempro). The incidence and duration of vaginal bleeding were assessed throughout the study. Statistical analyses used Cochran-Mantel-Haenszel methodology and analysis of variance. RESULTS: At 3 months, 1 mg norethindrone acetate/5 microg ethinyl estradiol therapy reduced the incidence of bleeding (12% vs 23%; P <.029) and bleeding and/or spotting (22% vs 44%; P <.001), compared with conjugated equine estrogens/medroxyprogesterone acetate therapy. The mean duration of bleeding and bleeding and/or spotting were also reduced with 1 mg norethindrone acetate/5 microg ethinyl estradiol therapy versus conjugated equine estrogens/medroxyprogesterone acetate (P =.004 and P <.001, respectively). The incidence of cumulative amenorrhea at every monthly interval was significantly better with 1 mg norethindrone acetate/5 microg ethinyl estradiol therapy versus conjugated equine estrogens/medroxyprogesterone acetate therapy (P <.05). Associated adverse event (ie, headache, breast pain) incidence rates were similar in the 2 active treatment groups. CONCLUSION: The 1 mg norethindrone acetate/5 microg ethinyl estradiol therapy provides significantly better control of vaginal bleeding than conjugated equine estrogens/medroxyprogesterone acetate therapy at all time points investigated in this 12-month study.

Adult↗
PubMedDate not supplied

Can we decrease breakthrough bleeding in patients with endometriosis on norethindrone acetate?

OBJECTIVE: To compare the breakthrough bleeding in endometriosis patients treated with Lupron-Depot alone, norethindrone acetate following Lupron-Depot, and norethindrone acetate alone. PATIENTS AND METHODS: 71 women with symptomatic surgically diagnosed endometriosis were retrospectively evaluated for this study. 28 women were treated with 6 doses of 3.75 mg Lupron-Depot every 4 weeks (Group I). 15 women were treated first with Lupron-Depot 3.75 mg every 4 weeks for 3 to 6 doses, followed by 5 mg norethindrone acetate (Group II). 28 patients were treated for 6 months with 5 mg per day norethindrone acetate alone (Group III). Breakthrough bleeding during treatment was scored mild (some spotting), moderate (lighter than patient's normal menstruation), or severe (as much as patient's normal menstruation or heavier). Multiple comparisons were done by ANOVA (SPSS) among three groups. The age of patients was not significantly different between groups 134.9-36.8 years). BMI of the three groups was significantly different 126.6 +/- 5.8, 27.4 +/- 6.4, 23.6 +/- 4.5, respectively). RESULTS: Breakthrough bleeding was reported by 14% of Group I, 20% of Group II, and 68% of Group III. CONCLUSION: Endometriosis patients who were treated with norethindrone acetate following Lupron-Depot had significantly less breakthrough bleeding than those given norethindrone acetate alone, and the incidence was comparable to Lupron-Depot alone.

Adult↗
PubMed1993

A clinical comparison of two triphasic oral contraceptives with levonorgestrel or norethindrone: a prospective, randomized, single-blind study.

Menstrual bleeding patterns were investigated in young women taking either a levonorgestrel triphasic, Triquilar, or a norethindrone triphasic, Ortho 7/7/7, two commonly prescribed low-dose oral contraceptives. The levonorgestrel triphasic contains ethinyl estradiol (EE) 30 micrograms + levonorgestrel (LNG) 50 micrograms for the first six days, EE 40 micrograms + LNG 75 micrograms for the following five days, and EE 30 micrograms + LNG 125 micrograms for the last ten days. The norethindrone triphasic contains EE 35 micrograms + norethindrone (NET) 0.5 mg for the first seven days, EE 35 micrograms + NET 0.75 mg for the following seven days and EE 35 micrograms + NET 1.0 mg for the last seven days. Three hundred women from 16 to 25 years of age were randomized to the levonorgestrel triphasic (n = 150) or the norethindrone triphasic (n = 150) groups. Assessments were made from daily diary cards and from bimonthly investigator interviews over 6 pill cycles. The results showed a higher incidence of intermenstrual bleeding (breakthrough bleeding and/or spotting) in the norethindrone triphasic group (NET group) than in the levonorgestrel triphasic group (LNG group): 44.9% of patients (66/147) randomized to the LNG group reported intermenstrual bleeding one or more times during the study compared with 61.9% (91/147) randomized to the NET group (p = 0.0036). Furthermore, in subjects who did not miss any pills, the proportion of patients with intermenstrual bleeding in each cycle was significantly greater (p < 0.02, cycles 1-4, 6; p > 0.05, cycle 5) and was experienced for more days per cycle (p < 0.05, cycle 1) and for more cycles per patient (p < 0.05, 5 cycles) in the NET group compared with the LNG group. Intermenstrual bleeding was also less frequently observed in the LNG group than in the NET group in patients who missed pills (p < 0.05, cycles 3, 5 and 6). In addition, early withdrawal bleeding occurred more often in the NET group than in the LNG group (p < 0.05, cycles 1, 3 and 4). The incidence of amenorrhea was similar in both groups. These results demonstrate a significantly lower incidence of intermenstrual bleeding and therefore better cycle control with the levonorgestrel triphasic Triquilar, compared with the norethindrone triphasic Ortho 7/7/7.

Adolescent↗
PubMed1991

The effects of norethindrone on the mullerian ducts of the American alligator.

Norethindrone, a reported aromatase inhibitor, has been used to examine the role of estrogens in the unilateral regression of the mullerian ducts that occurs in female chick embryos. The mullerian ducts are embryonic oviducts that regress in most male vertebrates under the influence of the testicular hormone, mullerian inhibiting substance (MIS). The ovaries of the chick also produce MIS during early development, but only the right duct regresses. Based on the finding that the left duct contains significantly more estradiol binding sites than the right duct, it has been proposed that the left duct is protected from the effects of MIS by preferentially binding estradiol from the ovaries. In support of this theory, norethindrone (0.1 and 0.5 mg) injected into the airsac of chick eggs results in regression of the left mullerian duct of female embryos, presumably by blocking the synthesis of estradiol. In the present study, it was hypothesized that crocodilians, because of the common ancestry they share with birds, would respond in a similar manner by exhibiting regression of both mullerian ducts in response to norethindrone. However, the application of norethindrone (0.5 mg) to the chorioallantoic membrane of female alligator embryos in ovo resulted in significant hypertrophy of the ducts, indicating that norethindrone had an estrogenic effect in the alligator rather than acting as an aromatase inhibitor. There was no effect of norethindrone on the gonads.

Alligators and Crocodiles↗
PubMed1983

Norethindrone acetate inhibition of triglyceride synthesis and release by rat hepatocytes.

The progestin, norethindrone acetate has been widely administered to patients in the form of oral contraceptives; however, its hypolipemic action has received little study. This report describes the effects of conventional doses of norethindrone acetate (100 micrograms/day.kg body weight 0.75) on rat plasma lipid levels in vivo as well as the mechanism of action on triglyceride metabolism in isolated hepatocytes in vitro. Norethindrone acetate administration led to significant and proportional reductions of the concentrations of triglycerides, cholesterol and phospholipids of plasma lipoproteins of density less than 1.006 of rats fed a high carbohydrate diet. Norethindrone acetate (0.1 mM) also significantly inhibited the incorporation of both [9,10(-3)H] palmitate and [U-14C]glycerol into triglycerides of isolated hepatocytes from fed rats, by 11 to 16% (P less than 0.001). Release of labeled triglycerides from the isolated hepatocytes was similarly inhibited, 21% and 46%, respectively (P less than 0.05). At the higher concentration of 1.0 mM, norethindrone acetate inhibited the incorporation of [2(-3)H]glycerol into hepatocytic triglycerides by 35-39% (P less than 0.05). The present findings suggest that inhibition of hepatic triglyceride synthesis can account for the reduction of hepatic triglyceride secretion and for at least part of the lowering of plasma VLDL levels which occurs during administration of norethindrone acetate in the rat.

Animals↗
PubMed1981

Destruction of liver haem by norethindrone. Conversion into green pigments.

1. Factors affecting the norethindrone-mediated conversion of hepatic haem into green pigments have been studied in the rat. Concentrations of haem and green pigments were estimated spectrophotometrically after esterification and separation by silica gel high-pressure liquid chromatography (h.p.l.c.). 2. Accumulation of green pigments in the liver was dependent on the dose of steroid and the time after dosing, maximum values being reached after 4-8h. Phenobarbitone pretreatment of rats resulted in an 8-fold increase in the concentration of green pigments at these times. 3. In microsomal systems in vitro, the formation of green pigments in the presence of NADPH and norethindrone was also dependent on the concentration of steroid and incubation times. Reaction rates very rapidly became non-linear with time, consistent with the self-catalysed destruction of the form(s) of cytochrome P-450 responsible for the metabolic activation of norethindrone. Microsomal mixtures incubated for a short period of time (1min) with norethindrone gave only one green-pigment peak after h.p.l.c. Longer incubation times gave four or five additional green pigments. Results suggested that multiple green pigments may arise by metabolic transformation of a single precursor. 4. When liver haem was prelabelled with (14)C by using 5-amino[4-(14)C]laevulinic acid, subsequent dosing with norethindrone in vivo gave rise to three major (14)C-labelled-green-pigment peaks on h.p.l.c. None of these components had the same retention times as the green pigments produced by microsomal fractions in vitro. 5. When liver haem was prelabelled with (59)Fe by using (59)FeCl(3), norethindrone administration resulted in the detection of (59)Fe-labelled green pigments if subsequent esterification was carried out under neutral conditions with trimethyloxonium tetrafluoroborate, but not when carried out under acidic conditions with methanol/H(2)SO(4). These results suggested that green pigments normally contain chelated iron and that metal-free green pigments are not produced by the liver.

Animals↗
PubMed1985

Unscheduled DNA synthesis caused by norethindrone and related contraceptive steroids in short-term male rat hepatocyte cultures.

The genotoxic potential of oral contraceptive steroids such as norethindrone was investigated in short-term rat hepatocyte cultures by measurement of unscheduled DNA synthesis. Norethindrone caused a small dose-dependent increase in unscheduled DNA synthesis in male rat hepatocytes as judged by the incorporation of [methyl-3H]thymidine into DNA. This was assessed either by liquid scintillation counting following isolation of DNA or by autoradiography. No increase in unscheduled DNA synthesis could be detected in female rat hepatocytes treated with norethindrone. Pre-treatment of male rats with phenobarbitone prior to hepatocyte preparation decreased the norethindrone mediated unscheduled DNA synthesis relative to control hepatocyte cultures while 3-methylcholanthrene pre-treatment had little effect. Unscheduled DNA synthesis in norethindrone treated control male rat hepatocytes was reduced by the mixed function oxidase inhibitors SKF 525A or metyrapone. In 24- or 52-hour-old hepatocyte cultures in which the cytochrome P-450 content was lower than in freshly prepared cells, or in a hepatocyte-derived cell line lacking cytochrome P-450, unscheduled DNA synthesis due to norethindrone was either decreased or abolished. Structure activity studies showed that only steroids containing a 17 alpha-ethynyl substituent caused an increase in unscheduled DNA synthesis.

Animals↗
PubMed1993

Effects of sodium etidronate in combination with low-dose norethindrone in patients administered a long-acting GnRH agonist: a preliminary report.

OBJECTIVE: To assess the efficacy of combining sodium etidronate with low doses of the 19-nor-testosterone progestin norethindrone or using high doses of norethindrone alone as prophylaxis against the vasomotor instability and bone density loss induced by GnRH agonists alone. METHODS: Eleven patients enrolled in this randomized study received the long-acting GnRH agonist leuprolide acetate 3.75 mg intramuscularly every 4 weeks for 24 weeks. Six patients (group I) self-administered sodium etidronate 400 mg/day orally for 14 days followed by calcium carbonate 500 mg/day orally for the next 42 days during three 56-day cycles. This regimen was supplemented by norethindrone 2.5 mg/day orally. Five patients (group II) self-administered norethindrone 10 mg/day orally. Two sets of controls were used. Group III consisted of ten previously reported patients who received the same GnRH agonist only. Group IV comprised 12 regularly cycling untreated controls. Bone mineral density, vasomotor symptoms, circulating estrogens, and lipids were assessed serially. RESULTS: The significant vasomotor instability (P < .01) and bone mineral density loss (-4.8 +/- 0.9%; P < .05) experienced by patients in group III was prevented in those in groups I and II despite maintenance of a persistent hypoestrogenic state. Bone density changes in groups I and II were similar to those in untreated controls (group IV). Persistent decreases in high-density lipoprotein (HDL) cholesterol (P = .005) and increases in the low-density lipoprotein-to-HDL ratio (P < .05) were noted only in group II patients receiving supplemental high-dose norethindrone. CONCLUSION: These preliminary data suggest that the addition of cyclic sodium etidronate in combination with low-dose norethindrone to GnRH agonists is an effective means of ameliorating the hypoestrogenic side effects induced by GnRH agonist alone.

Bone Density↗
PubMed2005

Treatment of symptomatic rectovaginal endometriosis with an estrogen-progestogen combination versus low-dose norethindrone acetate.

OBJECTIVE: To evaluate the efficacy, safety, and tolerability of an estrogen-progestogen combination versus low-dose norethindrone acetate in the treatment of persistent pain after surgery for symptomatic rectovaginal endometriosis. DESIGN: Randomized controlled trial. SETTING: Academic center. PATIENT(S): Ninety women with recurrent moderate or severe pelvic pain after unsuccessful conservative surgery for symptomatic rectovaginal endometriosis. INTERVENTION(S): Twelve-month, continuous treatment with oral ethinyl E2, 0.01 mg, plus cyproterone acetate, 3 mg/day, or norethindrone acetate, 2.5 mg/day. MAIN OUTCOME MEASURE(S): Degree of satisfaction with therapy. RESULT(S): Seven women in the ethinyl E2 plus cyproterone acetate arm and five in the norethindrone acetate arm withdrew because of side effects (n=5), treatment inefficacy (n=6), or loss to follow-up (n=1). At 12 months, dysmenorrhea, deep dyspareunia, nonmenstrual pelvic pain, and dyschezia scores were substantially reduced without major between-group differences. Both regimens induced minor unfavorable variations in the serum lipid profile. According to an intention-to-treat analysis, 28 (62%) out of 45 patients in the ethinyl E2 plus cyproterone acetate group and 33 (73%) out of 45 in the norethindrone acetate group were satisfied with the treatment received. CONCLUSION(S): Low-dose norethindrone acetate could be considered an effective, tolerable, and inexpensive first-choice medical alternative to repeat surgery for treating symptomatic rectovaginal endometriotic lesions in patients who do not seek conception.

Adolescent↗
PubMed2000

Norethindrone acetate and estradiol-induced endometrial hyperplasia.

OBJECTIVE: To identify the lowest effective continuous dose of norethindrone acetate that significantly reduces 12-month incidence of endometrial hyperplasia associated with unopposed 17beta-estradiol (E2), 1 mg. METHODS: In a double-masked, randomized, multicenter study, 1176 healthy postmenopausal women 45 years of age or older without evidence of endometrial abnormalities were given 12 months of treatment with unopposed E2, 1 mg, or continuous-combined regimens of E2, 1 mg, and norethindrone acetate, 0.1 mg, 0.25 mg, or 0.5 mg. Endometrial histology was evaluated at the end of the treatment period. RESULTS: Continuous-combined E2-norethindrone acetate regimens significantly reduced 12-month incidence of endometrial hyperplasia compared with unopposed E2 1 mg (P <.001). Endometrial hyperplasia occurred in 14.6% of women treated with unopposed E2 1 mg, whereas in all continuous-combined groups, the rate decreased to less than 1%. Among patients who received E2-norethindrone acetate 0.1 mg, incidence was 0.8%; among those who received 0.25 mg and 0.5 mg, it was 0.4%. CONCLUSION: Continuous norethindrone acetate at doses as low as 0.1 mg combined with E2 1 mg effectively negated risk for endometrial hyperplasia associated with unopposed E2 1 mg, at least for the first year of therapy.

Climacteric↗
PubMed1987

Influence of aspirin on the pharmacokinetics of norethindrone.

The influence of a single dose of aspirin on the pharmacokinetics of the synthetic progestogen norethindrone was studied in rabbits. It was found that neither the 24-hr plasma levels nor the pharmacokinetic parameters of norethindrone following intravenous dosing were significantly altered by aspirin. However, after oral administration of norethindrone, the area under the plasma norethindrone versus time curve was significantly decreased by aspirin from 0.72 +/- 0.058 ng/ml X hr to 0.49 +/- 0.046 ng/ml X hr (mean +/- S.E) and the oral bioavailability was reduced from 56 +/- 4.2% to 38 +/- 3.6%, perhaps due to increased gut wall metabolism of norethindrone by aspirin.

Animals↗
PubMed2003

Effect of topiramate or carbamazepine on the pharmacokinetics of an oral contraceptive containing norethindrone and ethinyl estradiol in healthy obese and nonobese female subjects.

PURPOSE: To study the pharmacokinetics of a combination oral contraceptive (OC) containing norethindrone and ethinyl estradiol during OC monotherapy, concomitant OC and topiramate (TPM) therapy, and concomitant OC and carbamazepine (CBZ) therapy in order to comparatively evaluate the pharmacokinetic interaction, which may cause contraceptive failure. METHODS: This randomized, open-label, five-group study included two 28-day cycles. Five groups of female subjects received oral doses of ORTHO-NOVUM 1/35 alone (cycle 1) and then concomitant with TPM or CBZ (cycle 2). The treatment groups were group 1, TPM, 50 mg/day; group 2, TPM, 100 mg/day; group 3, TPM, 200 mg/day; group 4, TPM, 200 mg/day (obese women); and group 5, CBZ, 600 mg/day. Group 4 comprised obese women whose body mass index (BMI) was between 30 and 35 kg/m(2). The BMI of the remaining four groups was < or =27 kg/m2. RESULTS: Coadministration of TPM at daily doses of 50, 100, and 200 mg (nonobese) and 200 mg (obese) nonsignificantly (p > 0.05) changed the mean area under the curve (AUC) of ethinyl estradiol by -12%, +5%, -11%, and -9%, respectively, compared with OC monotherapy. A similar nonsignificant difference was observed with the plasma levels and AUC values of norethindrone (p > 0.05). CBZ (600 mg/day) significantly (p < 0.05) decreased the AUC values of norethindrone and ethinyl estradiol by 58% and 42%, respectively, and increased their respective oral clearance by 69% and 127% (p < 0.05). Because CBZ induces CYP 3A-mediated and glucuronide conjugation metabolic pathways, the significant increase in the oral clearance of ethinyl estradiol and norethindrone was anticipated. CONCLUSIONS: TPM, at daily doses of 50-200 mg, does not interact with an OC containing norethindrone and ethinyl estradiol. The lack of the TPM-OC interaction is notable when it is compared with the CBZ-OC interaction.

Administration, Oral↗
PubMedDate not supplied

Effects of oral contraceptive norethindrone on blood-lipid and lipid peroxidation parameters.

Considering importance of the lipophilicity of norethindrone (log P=2.97), a significant contributor to its mechanism of action, interaction of the drug with total lipids of goat whole blood have been investigated using phospholipid binding, fatty acid composition and peroxidation phenomena as the parameters under investigation. The objective was to derive an insight into the pharmacodynamic behavior of the drug by correlating biological activity with drug induced changes in lipid constituents. Significant loss in phospholipid along with changes in fatty acid cotmposition was observed after incubation of whole blood with norethindrone at 56 ng/ml (effective contraceptive concentration in blood) in varying periods of time. This may be ascribed to binding affinity of norethindrone with lipid constituents in blood. Lipid binding potential of the drug may have a role in its therapeutic effect. Lipid peroxidation induction potential of norethindrone was quantitatively measured in the context of its toxicity. The results reveal that northindrone caused significant extent of lipid peroxidation. Ascorbic acid, a promising antioxidant, at equivalent human dose levels of 250 mg and 500 mg could significantly reduce norethindrone induced lipid peroxidation.

Animals↗
PubMed1975

Ultrastructural effects of mestranol and norethindrone on guinea pig endometrial stromal cell.

The effect of exogenous contraceptive steroids on the ultrstructural features of the endometrial stromal cells was studied in 64 guinea pigs allotted to 4 treatment groups. Four guinea pigs from each group were killed 14, 28, 56, and 84 days after treatment with mestranol (0.01 mg/day in 1 ml of oil) or with norethindrone (0.2 mg/day in 1 ml of oil) or with a combination of both (0.001 mg of mestranol/day and 0.02 mg of norethindrone/day in 1 ml of oil) or with 1 ml of vegetable oil (oil-treated controls). An additional 12 normal guinea pigs (nontreated controls) were killed during the follicular and luteal phases of the estrous cycle, and uterine specimens were immediately collected to determine base line characteristics. During estrus, the stromal cells of these 12 guinea pigs had abundant dilated rough endoplasmic reticulum. The interstitium was filled with collagen. During the luteal phase. the cytoplasm of the stromal cells of the 12 guinea pigs contained a prominent nucleus and rough endoplasmic reticulum with undilated cisterns. The interstitium contained sparse amounts of collagen. The stromal cells of the oil-treated control guinea pigs seemed similar in ultrastructure to the stromal cells of the 12 nontreated control guinea pigs at the luteal phase. Mestranol-fed guinea pigs had dilated rough endoplasmic reticulum and well-developed Golgi apparatus within 2 weeks of initial treatment. The interstitium of mestranol-treated guinea pigs had more collagen than that of the oil-treated controls and nontreated controls during the luteal phase. Prolonged treatment with mestranol caused extensive dilation of the cisternae of the endoplasmic reticulum. The interstitium was filled with abundant collagen. Pronounced alterations in the cytoplasmic organelles or extracellular connective tissue were not ovserved in guinea pigs given norethindrone alone or norethindrone in combination with mestranol for 14 days. The stromal cells closely resembled the cells of the mature animal at luteal phase. However, the dilated rough endoplasmic reticulum that occurred in cells after mestranol treatment was not seen in stromal cells after 84 days of treatment with norethindrone. Dilation of rough endoplasmic reticulum was also observed when both the contraceptive steroids were given simultaneously for 84 days. The increased and extensively dilated rough endoplasmic reticulum seen during the follicular phase and after mestranol administration or after 84 days of treatment with mestranol and norethindrone probably indicates increased protein synthesis by the endometrial stromal cells.

Animals↗
PubMed1985

Norethindrone disposition following x-ionizing radiation in rats.

The pharmacokinetics of norethindrone were investigated in rats exposed to ionizing x-irradiation. Norethindrone was administered by IV bolus injection immediately after, 3 days or 7 days after exposure to 100 rads, 300 rads, 600 rads, and sham x-irradiation. No observable change in norethindrone pharmacokinetics was observed in rats immediately after exposure to all dose levels of x-rays. At three days post irradiation there was an increase in volume of distribution (Vdarea) from 5.55 +/- 0.93 l/kg for sham irradiated to 11.28 +/- 0.74 l/kg for 600 rad rats. Half-life increased after exposure to x-rays from 45.2 +/- 4.5 minutes for sham irradiated to 85.5 +/- 12.1 minutes for 600 rads dose. The Mean Residence Time (MRT) increased from 56.7 +/- 5.6 minutes to 96.4 +/- 13.6 minutes after exposure to 600 rads. This same trend was present 7 days post irradiation but was not nearly as pronounced. No significant differences were observed in total body clearance in irradiated versus sham irradiated animals. As norethindrone is excreted as metabolites via hepatic biotransformation, these findings imply that this process is not affected by irradiation for drugs with high hepatic extraction ratios. Increased distribution of norethindrone to peripheral tissues results in a longer MRT for irradiated animals which could result from radiation induced increase in membrane permeability.

Animals↗