Disposition and clinical side effects of pentazocine when administered during day and night.

The question of possible circadian rhythm upon administration of 6,11-dimethyl-2,6-methano-3-(3-methyl-2-butenyl)-1,2,3,4,5,6-hexahydro-3- benzazocin-8-ol (pentazocine, Talwin) (which was found to exist in beagle dogs) was studied in eight healthy, male volunteers. Six of the subjects resided in the USA, and two subjects joined the study group the night before the morning experiment from Europe. All blood concentration-time data after i.v. injection starting between 8-9 a.m. and 8-9p.m., respectively, were best fit by biexponential curves. The derived pharmacokinetic parameters were essentially identical to those reported in the literature. Overall, no statistically significant differences were found for any of the parameters between the day and night study. However, the two volunteers from Europe demonstrated significant differences in the volume of distribution. Although the sample number is too small to draw final conclusions, it indicates the need for further studies regarding possible influences by offsetting the biologic clock, or "jet-lag" on drug disposition. No differences were found in clinical effects between the day and night study. However, all clinical effects were significantly more pronounced after the first than after the second dose, regardless of time of administration.

[Treatment of menstrual cycle associated migraine]. / Beitrag zur Behandlung der zyklusabhängigen Migräne.

A high percentage of migraine in women is closely related to the menstrual cycle either at the time of ovulation or in the perimenstrual period. It can be assumed that rapid serum fluctuations due to the decline of serum estrogens and or progesterone trigger this type of headache. With respect to a possible endocrine mechanism a hormonal treatment seems to be useful in order to avoid migraine or at least to decrease the complaints. Periovulatory migraine can be easily treated with oral contraceptives (o.c.). In women already taking o.c. with headaches in the perimenstrual period either low dose progestogens (minipill) or 0.5 mg estriol up to three times per day during the whole interval can be tried. In women not taking o.c. a corresponding therapy from day 20 of the cycle is indicated. It is important to choose the dosage to be neutral towards bleeding behavior.

[Obstetrical analgesia with tramadol]. / Geburtshilfliche Analgesie mit Tramadol.

Parenteral analgesia with Tramal was performed in 23 normal deliveries. The results were compared with a group of normal deliveries in which analgesia was achieved with pethidine. Both medicaments excerted an identical analgetic efficiency. No adverse side effects were observed with Tramal concerning the follow-up of labour or the newborn. Tramal can be recommended for obstetrical analgesia since it does not excert inhibitory effects upon the respiratory center.

[Inhibition of ovulation with 17-alpha-ethinyl-18-methyl-11-methylene-4-estren-17-ol plus ethinylestradiol]. / Zur Ovulationshemmung mit 17 alpha-Athinyl-18-methyl-11-methylen-4-östren-17-ol plus Athinylöstradiol.

A combined oral application of 30 micrograms ethinylestradiol with 50 micrograms 17 alpha-ethinyl-18-methyl-11-methylene-4-estren-17-ol (a newly developed progestagen) -- for 21 days resulted in a distinct antigonadotrophic effect, shown by hormone analysis (LH, FSH, estradiol and progesterone) in serum samples of three healthy and fertile women. A final recommendation on the daily dosage, however, depends on the results of clinical experimental investigation still in progress.

[Vaginal absorption of econazole]. / Untersuchungen zur vaginalen Resorption von Econazol.

After vaginal application econazol is absorbed to a high degree. Plasma levels are maintained for a relatively long period. Metabolism occurs in the vagina already. As there are no objections concerning toxicology the fact of absorption is considered positive from the therapeutical view-point because this drug does exert its effect not only in the vaginal cavity but also in the epithelium. It is suggested that vaginal absorption is influenced by cervical mucus.

[Circadian-induced change in the pharmacokinetic pattern exemplified on hexobarbital/Retrospective analysis of experimental data (author's transl)]. / Zirkadian bedingter Wechsel des pharmakokinetischen Modells am Beispiel von Hexobarbital. Retrospektive Analyse von Versuchsdaten.

The present study dealt with data from a study to evaluate circadian influences on the pharmacokinetics of hexobarbital. It could be seen that the pharmacokinetic model changes from an open one-compartment model to an open two-compartment model in dependence of the time of application. The curve fitting to an open two-compartment model reached high correlations when the test substance was applied at 18 h. The pharmacokinetic parameters to be evaluated did not fit to literature data. After application of the substance at 10 h in the morning the curve fitting to an open one-compartment model correlated highly. The pharmacokinetic parameters at this time comparable with the known literature.

[Circadian fluctuations of pharmacokinetic parameters after oral administration of hexobarbital (author's transl)]. / Zirkadiane Schwankungen pharmakokinetischer Parameter nach oraler Gabe von Hexobarbital.

To 4 male and 2 female subjects hexobarbital was applied orally at different times of the day: 2, 10, 18 h. Serum concentrations of hexobarbital were determined by HPLC procedure and the resulting pharmacokinetic parameters in a rotating iterative program. Application at 18 h resulted in a shorter invasion time, a higher maximum concentration and a delayed elimination; in addition, the AUC was elevated in relation to application at 2 or 10 h. In the 2 female subjects a different pattern was observed. The results lead to the assumption that application of hexobarbital is more effective in the evening than in the morning.

[Diagnosis of candidiasis by means of Microstix-Candida]. / Zur Diagnostik der Soorinfektion mittels Microstix-Candida.

The incidence of candidiasis was study in 115 mothers (vaginal) and their newborn infants (throat and fecal). Comparison studies employing Microstix-Candida and conventional Nickerson's media indicate a higher detection rate with the former. The detection of candida albicans in the newborn was obtained at an earlier time point and somewhat more frequently with Nickerson's medium.

[Human-pharmacokinetic Studies on Penetration Kinetics of a 6 alpha-Fluoro-9 alpha-chloro-16 alpha-methyl-delta 1,4-pregnadiene-11 beta-dihydroxy-3,20-dione-21-trimethyl-acetic acid (Clocortolone Trimethyl-acetic acid) after e picutaneous application]. / Human-pharmakokinetische Untersuchungen zur Penetrationskinetik eines 6 alpha-Fluoro-9 alpha-chloro-16 alpha-methyl-delta 1,4-pregnadien-11 beta-dihydroxy-3,20-dion-21-trimethylacetat (Clocortolon-trimethylacetat) nach epikutaner Applikation.

Investigation on 6 alpha-fluoro-9 alpha-chloro-16 alpha-methyl-delta 1,4-pregnadiene-11 beta-dihydroxy-3,20-dione-21-trimethylacetic acid (clocortolone trimethylacetic acid) are reported. The aim of the trial was to prove the penetration kinetics of the steriod into the skin. Three healthy female subjects took part in the investigations. They were treated with an oil-water emulsion of the substance on two spots on the back, after having observed alcohol abstinence. One of the treated spots was stripped after 30 min, the second after 60 min using the "Tesafilm" stripping method. The strips were then analysed gaschromatographically on the presence of clocortolone-trimethylacetic acid. It could be shown that the steroid penetrates into the skin up to the 12th-14th strips, building up a certain congestion of the substance at this time because of reaching the stratum corneum, as we suppose. At this place a depot is built of which probably only a very small or no permeation into the system occurs, as clocortolone could not be detected either in the subjects' serum nor in the urine.

[Diagnosis of candidid colpitis by Microstix -Candida (author's transl)]. / Zur Diagnostik der Soorkolpitis mittels Microstix -Candida

The increase in the clinical significance of candida albicans in gynecology, particularly the high incidence (candidiasis) in the pregnant woman, demand an easy, efficient and rapid method for the routine diagnosis of candida albicans. Microstix -Candida, a specially developed dry culture medium in miniature form, has been studied in comparison to the conventional Nickerson's Medium. Good agreement of the data was obtained in 425 patients. The main advantages are the ease of handling and the 24 hour incubation period. The observed difference in data obtained from the phase microscope examinations and the Microstix Candida cultured specimens are discussed in detail.