Calibration, quality control, and stability of a quantitative enzyme immunochromatographic method for therapeutic drug monitoring.

We describe a noninstrumented quantitative method for therapeutic drug monitoring (AccuLevel test) that uses a factory-calibrated unit test format and a novel single-level approach to quality control. The AccuLevel method is based on the principles of immunochromatography, which provides a number of convenient protocol advantages without sacrificing assay performance or quality assurance. Most of the benefits of the immunochromatographic method derive by virtue of the fact that quantification is dependent on enzyme migration rather than enzyme activity. Since migration height is almost solely a function of a highly stable, immobilized, dry antibody reagent, the AccuLevel test is extremely insensitive to environmental factors. The predictable and uniform dependence of quantification on antibody site concentration allows complete reliability with a single-level control. These features of stability, factory calibration, and unitized test components make the AccuLevel immunochromatography method amenable to new quality control schemes.

The effect of a progesterone-releasing intrauterine contraceptive device on uterine secretion of prostaglandin F2alpha and life-span of corpora lutea in the ewe.

Two studies were conducted to investigate the effect of a progesterone-releasing intrauterine contraceptive device (IUD) on uterine secretion of prostaglandin (PG) F2alpha associated with IUD-induced luteolysis in sheep. In bilaterally ovulating ewes receiving an IUD on day 3 (estrus = day 0) intrauterine release of progesterone (90 microgram per day) by the device did not prevent premature luteolysis or the increased concentration of PGF2alpha in uterine venous plasma on day 5 caused by conventional IUD's. In the second study a progesterone-releasing IUD (645 microgram per day) inserted adjacent to the intact ovary at unilateral ovariectomy on day 14 inhibited early luteolysis in the subsequent estrous cycle and reduced the uterine secretion of PGF2alpha on day 5, without affecting concentrations of progesterone in the peripheral circulation at the intervening estrus. It is suggested that locally delivered intrauterine progesterone can inhibit IUD-induced luteolysis in the ewe by suppressing the uterine secretion of PGF2alpha.

The effect of exogenous intrauterine progesterone on the amount and prostaglandin F2alpha content of menstrual blood in dysmenorrheic women.

Women with complaints of moderate or severe dysmenorrhea received intrauterine progesterone contraceptive system (16 patients) or placebo systems releasing no hormone (8 patients). Tampons were collected during the period prior to insertion and from 11 and 6 women, respectively, in the two groups at the second and fourth postinsertion periods. Prostaglandins in menstrual blood were extracted, and the amount and concentration of PGF2alpha analyzed for each patient. The menstrual blood loss (MBL) was determined by the method of Hallberg and Nilsson. The total PGF2alpha content was significantly lower in the group using progesterone systems than in the placebo group at collections 2 and 4 and was well below the preinsertion level; in placebo users the content tended to be slightly higher than it had been before insertion. The MBL increased approximately 60% above preinsertion levels in five of the six women using placebo units and decreased approximately 40% in 10 of 11 women with progesterone systems. Of the eight women in the progesterone group who had reported severe dysmenorrhea prior to insertion, seven reported an improvement; three of six in the placebo group reported a lower degree of improvement. These findings suggest that the decreased biosynthesis of PGF2alpha is a concomitant of intrauterine progesterone administration and may be a basis for the ability of the Progestasert system to diminish menstrual pain.

Preclinical evaluation of intrauterine progesterone as a contraceptive agent. I. Local contraceptive effects and their reversal.

PIP: This study compared the local effects on the rabbit reproductive tract of 10, 65, or 150 mcg of progesterone/day (4.4, 29.6, or 71.4 mcg/day/kg of body weight, respectively), released from a delivery system directly into the uterine lumen. In addition, the reversibility of the effects of progesterone treatment, at a rate of 10 mcg/day, on fertility was evaluated after system removal. Progesterone administered continuously and unilaterally at a rate of 10 mcg/day by intrauterine placement caused greater declines in fertility rations (embryos/corpora lutea) than those observed in animals bearing identical systems that released no hormone. Contralateral horns served as controls. Fertility reduction was greater for both placebo systems and progesterone systems (10 mcg/day) when placed in the upper 1/3 of the uterus than in the lower 1/3. After placebo and progesterone systems were removed, all groups rapidly regained their fertility. Embryonic mortality in all groups during treatment was comparable to that in control horns of animals unilaterally pregnant. Progestational effects were observed only in the treated horn at the lowest hormone release rate (10 mcg/day); with the higher doses, however, the endometrium of both horns was affected. Ovulation did occur during all treatment in all animals, except those receiving the highest dose, 150 mcg/day. The importance of both a localized placement effect and a localized progestational effect on contraceptive action was confirmed; however there was no effect on the ovulatory process from intrauterine progesterone delivered at a contraceptive dose.^ieng