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Biomedical subjects

E S Palva

Publications and source records attributed to E S Palva.

8 recordsLinked to original sources
PubMed1987

The value of comparative bioavailability studies of marketed drugs in drug control. An example with erythromycin stearate.

As a part of the quality control of drugs The National Medicine Control Laboratory in Finland has started comparative bioavailability studies of synonym preparations in human volunteers by taking all the products containing the same active ingredients for absorption studies at the same time. The first study, which is presented as an example of the importance of these studies, covered three erythromycin stearate preparations containing 250 mg of erythromycin. 12 volunteers took 2 tablets of every product at one week intervals in a cross-over fashion, and the serum erythromycin levels were measured microbiologically for 12 hr. Disintegration and dissolution tests were also performed. One of the products was coated with an acid-resistant film and was not dissolved in pH 1.2, whereas the conventional tablets lost all antimicrobial activity after 15 min in pH 1.2. In phosphate buffer, pH 6.6, all the tablets dissolved rapidly and retained antimicrobial activity. One of the conventional tablets showed only a 50% bioavailability as compared to the two others and was subsequently withdrawn from the market. Thus, it is important to conduct comparative post-marketing bioavailability studies with drugs which earlier have shown good bioavailability.

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PubMed1985

Gender-related differences in diazepam effects on performance.

In order to investigate the possible differences of diazepam effects in the two sexes, two placebo-controlled double-blind studies were conducted on healthy volunteer students. In one study the subjects received diazepam 10 mg alone or combined with 0.5 g/kg of alcohol in a parallel group design; in the other 0.2 mg/kg of diazepam or placebo were given in a cross-over manner. In both trials diazepam impaired the psychomotor skills of women more than men. The difference was similar in tasks measuring cognitive (digit symbol substitution), motor (balance of extraocular muscles) and sensory (critical flicker fusion) performances. Tapping speed was affected to a similar degree in both genders. Diazepam 10 mg did not cause impairment of body balance, a parameter sensitive to alcohol. The combined effect of diazepam and alcohol was of similar magnitude in both sexes in all objective tests. Subjectively the women felt themselves clumsier than did the men. The calming effect was similar in both groups. The results suggest that while the performance of women may be more vulnerable than men to impairment by diazepam they also are aware of it. The difference of effects is of such magnitude that it may cause bias in experiments unless carefully balanced groups are used.

Adult↗
PubMed1984

Naloxone-ethanol interaction in experimental and clinical situations.

The effect of naloxone on ethanol-induced impairment of psychomotor performance was studied in a series of three placebo-controlled, double-blind trials. In all trials, two successive intravenous injections of naloxone (0.4 and 2.0 mg) were given at an interval of 0.5-1.5 hours. Cross-over trials with healthy volunteers (n = 17) were performed in laboratory. In these conditions, naloxone alone had no effect on performance. Ethanol alone (1.0 and 1.5 g/kg) dose-dependently induced nystagmus and impaired coordination, reactions, hand cooperation, body balance, flicker discrimination and extraocular muscle balance. When naloxone was given after ethanol, the first injection reduced slightly but significantly ethanol-induced (1.5 g/kg) nystagmus, while the second injection did not enhance this counteraction any more. Other alcohol effects were not significantly antagonized by naloxone. The clinical part of the study, consisting of parallel groups of either naloxone (n = 11) or saline (n = 7) -treated alcohol-intoxicated (mean blood alcohol concentration 2.9 mg/ml) out-patients, most of them alcoholics, showed that no counteraction of alcohol inebriation (measured by clinical inebriation tests) was associated with the treatment with naloxone in the clinical situation either. Our results suggest that naloxone has no clinical significance in antagonizing ethanol intoxication. The inebriating effects of ethanol are not importantly mediated via central opioid mechanisms.

Adult↗
PubMed1982

Actions and interactions of diazepam and alcohol on psychomotor skills in young and middle-aged subjects.

Healthy pretrained men participated in three separate controlled double-blind and cross-over trials. There were 10 students in Trial I, 11 army officials or policemen aged 38-59 years in Trial II, and 11 students in Trial III. After single oral doses of diazepam 10 mg (D), placebo, alcohol 0.5 g/kg (A) or D+A, given at one-week intervals in balanced order, the psychomotor skills (choice reaction, tracking, attention, flicker fusion) were repetitively measured up to 2.5 hrs. Serum D concentrations were measured by gas chromatography. D alone impaired flicker fusion in trials I and II, and also reactive and coordinative skills in trial III. A alone slightly impaired skills and failed to potentiate D effects. Increasing age rendered the performance worse but this was due to increased base-line errors rather than to enhanced responses to D. Serum D concentrations tended to rise in the presence of A suggesting an inhibition of D demethylation by alcohol. Both total and free concentrations of D were similar in both age groups. The results suggest that in spite of unaltered sensitivity to D, middle-aged subjects have a lowered margin of safety when driving or using machinery under D treatment.

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PubMed1979

Acute and subacute effects of diazepam on psychomotor skills: interaction with alcohol.

Effects of diazepam and alcohol on psychomotor skills were measured in two trials. In the first one, 200 healthy students volunteered for a double-blind single-dose study. Three doses of diazepam (5, 10 and 20 mg) and alcohol (0.5, 0.8 and 1.2 g/kg) were used alone and combined to construct dose-response graphs. All doses of alcohol impaired divided attention while co-ordinative skills were impaired by the 1.2 g/kg dose. Diazepam alone did not impair reactive or co-ordinative skills whereas the combinations of diazepam and alcohol did so. To further elucidate the subactue effects, a double-blind randomized study was conducted administering 2 and 10 mg of diazepam t.i.d. for two weeks to 18 healthy volunteers. The psychomotor tests were performed on the 7th and 14th days of drug administration, and 0.5 g/kg of alcohol was given on either day. Diazepam 2 mg, alone or with alcohol, did not differ from placebo. 10 mg of diazepam slightly increased reaction times but not reaction mistakes, and impaired both co-ordination and attention. Alcohol did not enhance diazepam effects. We suggest that a development of tolerance to diazepam may compensate the deleterious interaction of the agents found in acute studies.

Adult↗
PubMed1978

Effect of active metabolites of chlordiazepoxide and diazepam, alone or in combination with alcohol, on psychomotor skills related to driving.

Interaction of the main metabolites of diazepam and chlordiazepoxide with alcohol was measured in two subacute double-blind cross-over experiments on 40 healthy, young volunteers. The drugs were administered for two week periods. The variables measured were choice reaction time and accuracy, eye-hand co-ordination, divided attention, flicker fusion, proprioception and nystagmus. Chlordiazepoxide lactam, methyloxazepam and oxazepam significantly enhanced the alcohol-induced impairment of psychomotor skills, whereas N-desmethyl-diazepam did so only exceptionally in certain subjects in the choice reaction test. It is concluded that diazepam-alcohol interaction on psychomotor skills is mainly due to the parent compound. No correlation between the serum level of the agents and the changes in performance were found.

Adult↗
PubMed1976

Effect of active metabolites of chlordiazepoxide and diazepam, alone or in combination with alcohol, on psychomotor skills related to driving.

The interaction of the main metabolites of diazepam and chlordiazepoxide with alcohol was measured in two double-blind crossover subacute experiments on 40 healthy young volunteers. The drugs were administered for 2 weeks each. The variables measured were choice reaction time and accuracy, eye-hand coordination, divided attention, flicker fusion, proprioception, and nystagmus. ChL, MO and O significantly enhanced the alcohol-induced impairment of psychomotor skills whereas DMD did so only exceptionally on some subjects in the choice reaction test. It is concluded that the diazepam-alcohol interaction on psychomotor skills is mainly due to the parent compound. No correlations between the serum levels of the agents and the changes of performance were found.

Adult↗