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Biomedical subjects

R A Edgren

Publications and source records attributed to R A Edgren.

At least 19 recordsLinked to original sources
PubMed1989

Pharmacokinetics of norethindrone: effect of particle size.

In 24 healthy women between the ages of 19 and 35 years who had not used oral contraceptive preparations for at least 60 days, it was found that the smaller the particle size of norethindrone (NET) administered, the higher was the plasma NET level obtained. Three different preparations having particle sizes of NET smaller than 250 microns, 44 microns or 10 microns were tested in a crossover pattern. The time required to reach maximum plasma concentration (Tmax) became shorter with decreasing particle size, 1.69 hr, 1.52 hr and 1.06 hr, respectively. As particle size was reduced, the maximum NET plasma concentration (Cmax) increased for the 3 different 1 mg NET preparations, i.e. 8.66 ng/ml, 10.53 ng/ml and 15.73 ng/ml. A trial with a 2 mg NET preparation made with NET utilizing the 44 microns same material displayed a Tmax similar to the 1 mg NET preparation having the same particle size while the Cmax reached a level of 17.56 ng/ml. The area under the plasma concentration versus time curve from 0-24 hrs and the extrapolated total area under the curve, increased with decreasing particle size. The use of a smaller particle size allows for more rapid dissolution or oral contraceptive tablets when measured in vitro; however, there is no evidence that such faster dissolution leads to a significant difference in efficacy. Oral contraceptive tablets have, since their inception, utilized both large and small NET particle size material in various preparations.

Administration, Oral↗
PubMed1989

Bleeding patterns with low-dose, monophasic oral contraceptives.

Cycle control over 12 months with low-dose oral contraceptives (OCs) was analyzed using calendars of bleeding on pill-taking days 1 through 21 (intermenstrual bleeding; IMB). One preparation contained 0.5 mg norethindrone and 0.035 mg ethinyl estradiol (NET + EE), the other 0.3 mg norgestrel and 0.03 mg ethinyl estradiol (Ng + EE). Half the subjects had previously used OCs containing greater than or equal to 0.05 mg estrogen (switch-over); the others had not previously used OCs for 2 months or more (fresh). Fresh subjects reported more IMB than switch-over subjects, especially during the first three cycles; IMB decreased over time for both groups. Ng + EE subjects had fewer IMB episodes during the early cycles than NET + EE subjects. Daily incidence of IMB formed a characteristic W-shaped curve in the NET + EE subjects that was most apparent in early cycles.

Adolescent↗
PubMed1989

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

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

Adult↗
PubMed1988

Drug interactions with oral contraceptives: compilation and analysis of an adverse experience report database.

Over 700 alleged OC/drug interactions were reported for antituberculous drugs, other antibiotics, anticonvulsants, antidepressants, and analgesics. Fewer than ten reports of OC/drug interactions were found involving antihistamines, thyroid hormone, vitamin C, antacids, ulcer medication, or diuretics. These may represent a set of OC/drug interaction problems that need to brought into medical awareness. Pregnancy is the first event reported when OCs appear to interact with another drug. However, menstrual disturbances are reported more often. BTB is the most frequently reported menstrual disturbance: it has been considered a warning signal that OC efficacy may be compromised. In such circumstances, contraceptive backup may be warranted. Reports of interference with OC efficacy have been most common for drugs used to treat tuberculosis, epilepsy, and depression, so patients and their physicians should be aware of potential problems. However, the average woman is more likely to encounter antibiotics, analgesics, and antihistamines, and current package inserts contain appropriate warnings. In recent years, prescriptions for low-estrogen OCs have outnumbered those for high-dose preparations. Many physicians became concerned that there was an increased risk of OC drug failure with the low-dose products. The database does not seem to suggest that this has happened. The dose of estrogen is not correlated with total adverse experience reports, time of appearances of the first adverse experience reports, or rate of reporting of the interactions. Likewise, reports of potential interactions with menstrual disturbances are not correlated with lower estrogen doses in OCs. There is, however, an association between low-estrogen OCs and recently reported pregnancies attributed to OC/drug interactions.(ABSTRACT TRUNCATED AT 250 WORDS)

Contraceptives, Oral↗
PubMed1986

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

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

Absorption↗
PubMed1983

Steroid-induced thrombogenesis in rats.

Oral contraceptives have been associated with the development of thrombotic episodes in humans in various epidemiologic studies. Studies in laboratory animals have failed to provide evidence that sex hormones cause increased thromboses. Uzunova, Ramey, and Ramwell published data suggesting that male animals had more severe clotting problems following cannulation of the aorta than females, and that such problems were exacerbated by testosterone and ameliorated by estradiol. We attempted to confirm the testosterone effect and to extend the observations to such androgenic progestogens as norgestrel and norethindrone, and to ethinylestradiol, the estrogenic component of many oral contraceptives. None of these steroids had any measurable effect on cannula-induced thrombogenesis in rats, nor were "prothrombin times" affected. We conclude that another potential model for thrombogenesis in laboratory animals has failed to provide evidence for the putative effect of oral contraceptives in women.

Animals↗
PubMed1982

Elevated blood pressure following LHRH antagonists in rats.

LHRH and three potent antagonistic analogs: z-[Gln1, des-His2,D-Pse6,des-Gly10]-LHRH ethylamide, where D-Pse = threo-D-phenylserine; z-[Gln1,des-His2,D-Phe6,des-Gly10]-LHRH ethylamide; and Boc-[Ser(Bzl)1,des-His2,D-Trp6]-LHRH; were studied for their effects on blood pressure and heart rate in chronically catheterized conscious normotensive and hypertensive rats. All three analogs caused acute increases in blood pressure in normotensive male Sprague-Dawley rats; the z-Gln-Phenylalanine derivative also raised blood pressure in spontaneously hypertensive rats of Kyoto-Wistar origin. LHRH itself had no effect in either normotensive or hypertensive animals. The antagonistic analogs were also associated with acute toxicity. It is concluded that the antagonist analogs of LHRH, unlike LHRH itself, have significant acute cardiovascular effects in rats. Although the mechanism of these effects is not known nor is it known whether they occur in other species, the present data emphasize the need to define further the pharmacological profiles of these potent, biologically active materials.

Animals↗