A two-centre, open-label, randomised study of ovulation inhibition with three transdermal contraceptive patches, each containing different amounts of ethinyl estradiol and gestodene in healthy, young women.

Here we report the findings of a two-centre, open-label, randomised, Phase IIa study designed to investigate whether an ethinyl estradiol (EE)/gestodene (GSD) patch that has been developed (referred to herein as the 'EE/GSD patch') reliably inhibits ovulation in comparison with patches delivering lower doses of these hormones. The study rationale was to provide justification of the doses of EE and GSD selected for the EE/GSD patch. Healthy women, aged 18-35 years, were randomised to receive treatment with either the EE/GSD patch, a 'reduced-GSD patch' (delivering similar amounts of EE and approximately half the amount of GSD) or a 'reduced-EE/GSD patch' (delivering half the amount of EE and GSD). Treatment was administered for three 28-day cycles (three × 7 patch-wearing days, plus a 7-day patch-free interval). The primary pharmacodynamic variable was the percentage of women with ovulation in at least one of Cycles 2 and/or 3, as indicated by Hoogland score. Pharmacokinetic parameters for EE and GSD were also measured. Results indicated that the EE/GSD patch effectively suppressed ovulation, while patches delivering lower doses of EE and GSD were less effective for this purpose. All three patches showed comparable tolerability.

Effect of the antiprogestin onapristone on follicular growth in women.

The effects of the antiprogestin onapristone on the menstrual cycle were assessed in surgically sterilized volunteer women. The steroid was given orally at the dose of 5, 15 or 50 mg/day, from day 5 to day 11 of the cycle. Ovarian ultrasonography and hormonal determinations in plasma and urine were used to monitor the pre-treatment, treated and post-treatment cycles. Onapristone, given at a dose of 5 mg/day, affected follicular growth inconsistently. The dose of 15 or 50 mg/day arrested follicular growth and oestradiol increase and delayed gonadotrophin surge, extending the length of the follicular phase in five of seven women in each group. After discontinuation of treatment the leading follicle resumed its growth and ovulation occurred as judged by the elevation of plasma progesterone, preceded in most but not all cases by an echographic image of follicular collapse. The ensuing luteal phases were not significantly altered in length or plasma progesterone concentration. Cortisol concentrations were unaffected and no serious side-effects were recorded. The antifolliculotrophic effect of onapristone demonstrated here, together with previous reports of similar activity of mifepristone in women, indicate that this may be a general property of compounds that interfere with progesterone receptor function.

Determination of onapristone and its N-desmethyl metabolite in human plasma or serum by high-performance liquid chromatography.

An automated reversed-phase high-performance liquid chromatographic method for the determination of the antiprogestin onapristone and its N-desmethyl metabolite in human plasma or serum is described. Ultraviolet detection was performed at 315 nm, with a limit of detection of 1 ng/ml at a signal-to-noise ratio of 3. The intra- and inter-assay precision were less than or equal to 6% and less than or equal to 7%, respectively. Onapristone and its N-desmethyl metabolite were stable in human plasma. The method was successfully applied to serum samples obtained from human volunteers after oral administration of onapristone.

[Oral contrast media for magnetic resonance tomography of the abdomen. 1. Comparative animal studies of positive and negative contrast media]. / Orale Kontrastmittel für die magnetische Resonanztomographie des Abdomens. Teil 1: Tierexperimenteller Vergleich positiver und negativer Kontrastmittel.

Beagle dogs were investigated by MRI (Siemens Magnetom, 0.35 T) after oral administration of aqueous solutions of Gd-DTPA (n = 4), ferric ammonium citrate (n = 1), and magnetite dextran (n = 2). High signal intensity of the GI-tract versus adjacent structures was obtained with Gd-DTPA and ferric ammonium citrate. Magnetite showed negative contrast versus adjacent structures. However, magnetite displayed lower contrast relative to liver, muscle and gut wall compared to Gd-DTPA and ferric ammonium citrate. In relatively T2-weighted sequences labeling of poorly filled bowel loops was significantly better with Gd-DTPA and ferric ammonium citrate. For GI-tract contrast enhancement we conclude that positive contrast media are of higher diagnostic value compared to negative contrast agents.

Mechanism of renal excretion of various X-ray contrast materials in rabbits.

The excretory behavior of nine nephrotropic contrast agents with varying physicochemical properties such as charge, lipophilicity, and molecular size was investigated. Renal clearance in comparison with inulin was determined by means of the continuous infusion method. Each contrast agent was infused at three dose levels in four to six rabbits. The investigations show that tubular transportation in proportion to glomerular filtration decreases with increasing dosages of all the contrast agents. Thus, with the highest concentration in plasma all contrast agents are eliminated at more or less the glomerular filtration rate (GFR). After administration of the low dosages the following differences are found: 1) Net tubular secretion increases for the monomeric contrast agent acids with increasing lipophilicity, in the order diatrizoate congruent to iothalamate less than iodamide less than acetrizoate. 2) The clearance studies do not reveal any tubular secretion or reabsorption for a hydrophilic cationic contrast agent. 3) The nonionic contrast agents do not show net secretion. The more lipophilic they are, the more they are reabsorbed. 4) Two dimeric contrast agents also do not reveal any tubular secretion. They seem to be reabsorbed more than monomers with the same charge.