[Does grapefruit juice increase the bioavailability of orally administered sex steroids?]. / Zvysuje grapefruitová stáva dostupnost orálne podaných sexuálních steroidu?

OBJECTIVE: To verify if and to which extent the interaction with grapefruit juice can increase bioavailability of orally administered sexual steroids. DESIGN: Pilot pharmacokinetics study. SETTING: Department of Obstetrics and Gynecology and Institute of Pharmacology, Medical Faculty, Palacký University, Olomouc; Department of Nuclear Medicine, University Hospital, Olomouc. METHODS: 2 mg of estradiol valerate and 100 mg of micronized progesterone were given to eight healthy postmenopausal volunteers. Blood samples were collected at time 0, 2, 3, 5 and 24 hours after tablets application. The same trial was repeated a week later but tablets were swallowed with 200 ml of grapefruit juice. Serum levels of estradiol and progesterone were measured by RIA. Results were statistically evaluated using the Wilcoxon's nonparametric paired test. RESULTS: Though grapefruit juice on average slightly increased serum levels of estradiol (E2) and progesterone, this increase reached statistical significance only for the E2 level 24 hours after application of tablets. The mean area under curve (AUC) of estradiol rose significantly to 117%. The even greater increase in the mean AUC of progesterone (to 125%) was not statistically significant because of marked individual variability of response. CONCLUSIONS: Our results suggest that grapefruit juice may increase bioavailability of orally administered estradiol and progesterone. The response varies markedly between individuals. This observation may be of some importance also for users of OC and HRT.

[Personal experience with lovastatin, a HMG-CoA reductase inhibitor (Mevacor, MSD) in the treatment of hypercholesterolemia]. / Nase zkusenosti s inhibitorem HMG-CoA reduktázy lovastatinem (Mevacor, MSD) v lecbe hypercholesterolémie.

The authors administered lovastatin (Mevacor, MSD) to 18 patients with primary hyperlipoproteinaemia (familial and non-familial) with a lipoprotein pattern type IIa and IIb. During treatment a marked reduction of atherogenic indicators of the lipid metabolism occurred, i.e. a decline of total cholesterol (-28.6%), LDL-cholesterol -39%), apolipoprotein B (-18.6%), the index of total cholesterol/HDL-cholesterol (-44.6%) and the index LDL-cholesterol/HDL-cholesterol (-48.2%). At the same time a favourable effect on indicators of the lipid metabolism to which a protective action is ascribed was recorded: a rise of HDL-cholesterol (+13.6%) and apolipoprotein AI (+13%) and AII (+13%). An excellent effect was observed also in four heterozygotes with familial hypercholesterolaemia which is usually rather resistant to other types of hypolipidaemic treatment. The drug was very well tolerated and subjective side-effects of treatment were minimal. Despite the fact that a number of laboratory indicators was followed up, the authors did not observe any undesirable side-effects, only a transient and marginal rise of ALT in one patient. Lovastatin is, due to its potent hypolipidaemic effect, a new hope in the treatment of hypercholesterolaemia. Its usefulness in the prevention of ischaemic heart disease, as well as its safety during prolonged administration are tested at present in long-term investigations.

Comparative study of midazolam and diazepam in premedication of bronchoscopy.

Two types of benzodiazepines were used in premedication of flexible bronchoscopy. The agents were introduced in randomized, double-blind trial. Midazolam (Dormicum Hoffmann-La Roche AG) was given to 21 patients (0.07 mg/kg i.v.), diazepam (Seduxen Richter) to 22 patients (0.14 mg/kg i.v.) and placebo (saline) to 20 patients (0.07 ml/kg i.v.). Vigility, motor functions and anxiety were estimated from the application to 3 hours after endoscopy. Breathing, pulse rate, blood pressure and local reactions were followed as well. The course of bronchoscopy, anterograde amnesia and acceptability of further intervention were evaluated. Midazolam offered short term action, stronger sedative and anxiolytic effect than diazepam (48% to 27%). The anterograde amnesia was more frequent (90.5% to 55% in diazepam), acceptability of further bronchoscopy after midazolam was present in 95% of patients, after diazepam in 86% of patients. These favourable properties can be utilized especially in cases with enhanced anxiety and necessity of further endoscopies.

[Clinical trial of Pilogel HS made by Alcon]. / Klinické zkousení prípravku Pilogel HS firmy Alcon.

The authors give an account on the results of clinical tests of the anti-glaucomatous preparation PILOGEL HS of ALCON Co. The drug replaced in all groups of patients reliably 1-3% Pilocarpine administered three times a day, as regards its effect on intraocular tension. Its great practical advantage is that the effect is achieved after a single administration per 24 hours (at night). In particular patients in their productive age appreciate this advantage. The preparation was included in the import plan.

[Comparison of the results of therapy with vinblastine iontophoresis in post-diskectomy syndromes and other painful conditions]. / Srovnání výsledku lécby vinblastinovou iontoforézou u postdiskotomických syndromu a u jiných algických stavu.

The authors tested in 36 patients treatment of chronic intractable pain by percutaneous iontophoretic administration of an inhibitor of microtubular transport, Vinblastine inj. (G. Richter, Hungary). The groups comprised: (1) 16 patients with severe radicular pain after one or several operations of prolapsed lumbar intervertebral discs, (2) 20 patients with severe pain in the area of radicular dermal zones or dermal innervation areas of peripheral nerves. In every patient a minimum of 15 procedures were tried. Evaluation of the therapeutic effect was based on subjective data of the patient on the mitigation of pain in per cent, on the intensity of the current pain and the interference of the intensity of pain with daily activities. According to all criteria improvement was achieved in 31 subjects, i.e. in 86%. A favourable effect of treatment was observed after the 8th-10th administration. In the first group of patients clinically significant mitigation of algic symptoms was achieved in 69% of the treated subjects. In the second group a therapeutic effect was achieved in 90% of the patients. A marked difference between the two groups was found with respect to mitigation of the intensity of pain on completion of treatment. The mean mitigation of pain intensity in the first group was 24.1%, in the second group 47.7%. This difference is highly significant. With the exception of one female patient always a positive effect at the site of administration (beneath the anode) was observed.

Vinblastin iontophoresis in treating intractable pain.

A group of 36 patients were tested for the effects of percutaneous iontophoretic application of Vinblastin inj., a microtubular transport inhibitor (Gideon Richter, Hungary) in the treatment of chronic intractable pain. The group is divided into two subgroups: (1) 16 patients with persistent root pain following one or more operations for lumbar intervertebral disk herniation. (2) 20 patients with persistent pain in the area of the radicular skin zones or in the skin innervation areas of peripheral nerves. Vinblastin was injected in the place of maximal pain, 0.01% concentration in the total amount of 5 mg of active substance. The active electrode was the anode. There were at least 15 procedures per patient. The therapeutic effect was evaluated from the patients' subjective reports on pain relief in per cent, from the intensity of actual pain and from the interference of pain intensity with daily activities. Considering all the criteria, an improvement was achieved in 29 cases, i.e. 81%. The beneficial effect of the therapy was observed from the 8th to 10th application. In the first group of patients, 69% showed a clinically significant relief of the algetic symptoms. In the other group, the therapeutic effect was 90% of cases. A significant difference between both these groups was found to be in the degree of pain relief after the end of therapy. In the first group the average pain relief was 22.2%, in the other one 47.7%. This difference is statistically highly significant. Except for one case, the beneficial effect was always recorded in the place of administration (under the anode). Apart from local skin irritation in 2 patients and spot burns under the electrode in 2, no other side adverse effects were seen in the course of therapy, after its termination or at the checks made after some time interval (maximum 3 years).

[Iontophoretic administration of vinblastine in the control of refractory spinal root pain and postherpetic neuralgia]. / Iontoforetická aplikace vinblastinu k ovlivnení refrakterních korenových bolestí a postherpetické neuralgie.

Iontophoretic administration of substances which influence the function of microtubuli in the peripheral nerves is one of the new ways how to suppress some types of refractory chronic pain. Based on a number of experimental data and encouraging clinical results, the authors used in the submitted work repeated iontophoretic administration of 0.01% Vinblastine (G. Richter, Hungary) into the painful zone in a group of 20 patients with several types of non-malignant pain. Objectivization of the evaluation was partly also due to the authors' own version of McGill Pain Questionnaire, along with the graphic presentation of algetic zones. Clinically detectable mitigation of pain was achieved in 14 subjects, in eight improvement persisted for more than six months and one year resp. No serious undesirable side-effects were observed in the investigated subjects.

[Pathogenesis of embolotoxic reactions]. / Die Pathogenese der embolo -- toxischen Reaktion.

Own investigations concerning the principal mechanisms of Hoigné's syndrome demonstrated that the phenomenology of embolotoxic reactions depends in certain pre-conditions on high pressure during a rapid injection with the result of penetration of the drug into the blood stream. The occurrence of the syndrome and its symptomatology depend on the size of the crystals or lipid droplets that enter the blood stream, on the solubility of the crystals in the body, on the toxicity of the components of a particular drug and on the volume of the injected drug that enters the blood vessels. For the reasons mentioned above the symptomatology of the syndrome is variable and depends on the type of medicament applied.