A large observational clinical evaluation of a desogestrel-containing combiphasic oral contraceptive in Germany.

OBJECTIVE: The aim of this observational study was to assess the influence of a new combiphasic oral contraceptive on cycle control, tolerability and acne in a large cohort of women who wanted to switch from their previous oral contraceptive. METHODS: A total of 2,280 women were enrolled in this clinical evaluation at 232 centers in Germany. All women switched from their previous pill to a combiphasic oral contraceptive containing ethinylestradiol and desogestrel (combiphasic EE/DSG; comprising 25 microg desogestrel and 40 microg ethinylestradiol for 7 days followed by 125 microg desogestrel and 30 microg ethinylestradiol for 15 days and then a 6-day pill-free interval) for three cycles. RESULTS: Most women (53%) had previously used a monophasic oral contraceptive containing 20 or 30-35 microg ethinylestradiol. The most frequent reasons for switching were bleeding irregularities (41% of women), other menstrual disorders (27%) and migraine/headache (10%). After switching to combiphasic EE/DSG, cycle control improved significantly: the incidences of spotting and breakthrough bleeding decreased from 33% and 23% of women, respectively, before the start of the study, to 7% and 3% of women at the end of the study period. At the end of the study, acne was no longer present in 37% of the 592 women who had acne at the start of the study, and subjective complaints such as headaches were less frequent than before. Most women were satisfied or very satisfied with the combiphasic oral contraceptive and 89% wished to continue using it. CONCLUSIONS: The results of this observational clinical evaluation indicate that in everyday use, for women who wish to switch from another oral contraceptive, combiphasic EE/DSG is an effective and well-tolerated oral contraceptive, which improves cycle control and has a beneficial effect on acne.

Multicenter study of the efficacy, cycle control and tolerability of a phasic desogestrel-containing oral contraceptive.

OBJECTIVE: To investigate the efficacy, cycle control and tolerability of a phasic oral contraceptive containing ethinylestradiol 35/30/30 microg and desogestrel 50/100/150 microg. METHODS: A multicenter study was conducted involving 2070 healthy, fertile women, who received study treatment for six treatment cycles. RESULTS: Most of the participants (79%) had previously been using an alternative oral contraceptive. In 10,408 treatment cycles, two women became pregnant while on treatment (Pearl index, 0.25). The incidence of irregular bleeding was 10% before treatment, rising to 27% at cycle 1, and decreasing to 11% by cycle 6. Irregular bleeding was mainly due to spotting rather than breakthrough bleeding and the incidence of breakthrough bleeding remained below 2.2% for most of the study period. Only 1.8% of women withdrew due to bleeding irregularities. First-time oral contraceptive users initially experienced more irregular bleeding than switchers but these differences lessened over time. The most common adverse events during treatment were headache, breast tenderness and nausea. The incidence of these adverse events fell to below pretreatment levels with continued use. CONCLUSION: The phasic preparation was effective and well tolerated.

The National Leprosy Control Programme of Zimbabwe a data analysis, 1983-1992.

Prevalence and detection rates of leprosy in Zimbabwe as well as patient characteristics were reported by the National Leprosy Control Programme over the 10-year period 1983-1992. The control programme made a new start in 1983 when multidrug therapy was introduced. Prevalence per 10,000 population declined steeply from 3.78 in 1983 to 0.52 in 1987. Prevalence continued to decline to 0.22 in 1992 and was highest in the north-eastern provinces. After an initial increase, the detection rate per 10,000 had declined from 0.19 in 1985 to 0.08 in 1992. The proportion of refugees among new cases had gradually increased since 1988 and amounted to one third in 1991 and 1992. An analysis of records of 802 cases who were newly detected from 1983 to 1992 showed that 51% were of the multibacillary (MB) type, 33% had visible disabilities at detection, 5% were under 15 years of age while the average delay time was 2.6 years. Patients with disabilities reported a longer delay time, were more often men and had more often the MB type of leprosy. The data suggest that transmission of leprosy is low but that cases are not diagnosed early enough to prevent transmission altogether.

A comparison of the cycle control and tolerability of two ultra low-dose oral contraceptives containing 20 micrograms ethinylestradiol and either 150 micrograms desogestrel or 75 micrograms gestodene.

OBJECTIVE: To compare the cycle control and tolerability of two oral contraceptives containing 20 micrograms ethinylestradiol and either 150 micrograms desogestrel or 75 micrograms gestodene. METHODS: A randomized, multicenter study was conducted in which 1016 healthy adult women received the desogestrel (n = 509) or the gestodene (n = 507) preparation for six treatment cycles. RESULTS: No significant differences in bleeding patterns were detected between the two treatments. The incidence and duration of irregular bleeding decreased markedly, and to a similar extent, during each treatment. The occurrence of irregular bleeding per cycle decreased from 24.6 to 9.4% in the desogestrel group and from 19.7 to 8.6% in the gestodene group. Its duration fell from 1.1 to 0.2 days and from 0.9 to 0.3 days, respectively. There was a consistently low incidence of amenorrhea (1.0-2.8%). There were no significant differences between treatments for the incidence, intensity or emergence of dysmenorrhea. During both treatments, the incidence of premenstrual syndrome and complaints such as breast tenderness, nausea and headache dropped markedly. CONCLUSION: Ultra low-dose oral contraceptives containing desogestrel or gestodene offer equivalent, good cycle control and improvements in dysmenorrhea and premenstrual syndrome and have similar, excellent tolerability profiles.

The effects of cimetidine, ranitidine and famotidine on the single-dose pharmacokinetics of naproxen and its metabolites in humans.

We studied the effects of cimetidine, ranitidine and famotidine on the kinetics of naproxen. The mean t1/2 beta of naproxen in 6 subjects was 25.7 +/- 5.4 h (range 16 to 36). Naproxen acyl glucuronide accounts for 50.9 +/- 6.9% of the dose, its isomerized isoglucuronide for 6.8 +/- 2.6%, O-desmethylnaproxen acyl glucuronide for 14.3 +/- 4.1% and its isoglucuronide for 5.5 +/- 1.5% (n = 6). Naproxen (1.3 +/- 1.1%) and O-desmethylnaproxen (0.6 +/- 0.4%) are excreted in negligible amounts. Cimetidine, ranitidine and famotidine all reduced significantly the t1/2 beta of naproxen by 50% from 25 h to 13 h and the t1/2 alpha from 4.0 h to 1.1 h. No effect of the H2 antagonists was observed on the absorption of naproxen. They also reduced the Vss of naproxen by 50%. The amount of naproxen acyl glucuronide, naproxen isoglucuronide and O-desmethylnaproxen acyl glucuronide excreted in the urine, remained unchanged, 60%, 7%, and 14% respectively.

The pharmacokinetics of naproxen, its metabolite O-desmethylnaproxen, and their acyl glucuronides in humans. Effect of cimetidine.

1. The pharmacokinetics of 500 mg naproxen given orally were described in 10 subjects using a direct h.p.l.c. analysis of the acyl glucuronide conjugates of naproxen and its metabolite O-desmethylnaproxen. 2. The mean elimination half-life of naproxen was 24.7 +/- 6.4 h (range 7 to 36 h). 3. Naproxen acyl glucuronide accounted for 50.8 +/- 7.3% of the dose recovered in the urine, its isomerised conjugate isoglucuronide for 6.5 +/- 2.0%, O-desmethylnaproxen acyl glucuronide for 14.3 +/- 3.4%, and its isoglucuronide for 5.5 +/- 1.3%. Naproxen and O-desmethylnaproxen were excreted in negligible amounts (< 1%). 4. Even though the urine pH of the subjects was kept acid in order to stabilize the acyl glucuronides, isomerisation took place in blood. 5. The extents of plasma binding of the unconjugated compounds were 98% (naproxen) and 100% (O-desmethylnaproxen), while naproxen acyl glucuronide binding was 92%; that of its isomer isoglucuronide 66%. O-desmethylnaproxen acyl glucuronide was 72% bound and its isoglucuronide was 42% bound. 6. Cimetidine (400 mg twice daily) decreased the t1/2 of naproxen by 39-60% (mean 47.3 +/- 11.5%; P = 0.0014) from 24.7 +/- 6.4 h to 13.2 +/- 1.0 h. It increased (10%) the urinary recovery of naproxen acyl glucuronide (P = 0.0492). The urinary recoveries of naproxen isoglucuronide and O-desmethylnaproxen acyl glucuronide remained unchanged.

O-Dealkylation and N4-acetylation of sulpha-2-monomethoxine by the turtle Pseudemys scripta elegans.

Sulpha-2-monomethoxine is N4-acetylated to an extent of 12% of the dose by Pseudemys scripta elegans; 48% is excreted unchanged. No O-dealkylation of the 2-methoxy group takes place.

N2-glucuronidation and N4-acetylation of sulphaphenazole by the turtle Pseudemys scripta elegans.

After an oral dose of 100 mg of sulphaphenazole, the turtle Pseudemys scripta elegans excretes 27% of the compound unchanged and 3.8% as N4-acetylsulphaphenazole. The expected glucuronide conjugate, sulphaphenazole-N2-glucuronide, is not formed and excreted.

O-demethylation and N4-acetylation of sulfadimethoxine by the snail Cepaea hortensis.

The snail Cepaea hortensis O-dealkylates sulfadimethoxine at the 2- and 6-position, the 2-position being favoured. Sulfadimethoxine is also acetylated, while no measurable acetylation of the hydroxy (= demethyl) metabolites took place.

Oxidation and acetylation of sulfamonomethoxine by the snail Cepaea hortensis.

Sulfamonomethoxine is not O-demethylated in the snail Cepaea hortensis, but acetylated (15.2%) and oxidised (0.78%) at the 2 position of the pyrimidine nucleus.

Acetylation, deacetylation and hydroxylation of sulphamethoxazole and N4-acetylsulphamethoxazole in the snail Cepaea hortensis.

The snail Cepaea hortensis is able to acetylate and hydroxylate sulphamethoxazole in a similar way to man. About one percent deacetylation, but no hydroxylation of N4-acetysulphamethoxazole takes place. The relative rates of the metabolic pathways for hydroxylation and acetylation of sulphamethoxazole are equal.

Acetylation and hydroxylation of sulphatroxazole in the snail Cepaea hortensis and the slug Arion rufus.

The snail Cepaea hortensis can acetylate and hydroxylate sulphatroxazole via a pathway similar to that in man. The principal metabolic pathways, in order of decreasing rate, are hydroxylation, glucuronidation and acetylation. The slug Arion rufus also can acetylate and hydroxylate sulphatroxazole, although, in contrast to the snail, is rate of acetylation is higher than that of hydroxylation.