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Biomedical subjects

A Darragh

Publications and source records attributed to A Darragh.

At least 55 records · Page 3Linked to original sources
PubMed1983

Bioavailability of isosorbide dinitrate and its two mononitrate metabolites from sustained-release formulations.

Plasma concentrations and bioavailability of isosorbide dinitrate (ISDN) and its active metabolites isosorbide 2-mononitrate (2-ISMN) and isosorbide 5-mononitrate (5-ISMN) from two sustained-release formulations and one standard-release formulation of isosorbide dinitrate were compared. Means of peak drug concentrations of ISDN, 2-ISMN, and 5-ISMN after administration of the 20-mg sustained-release formulation were 5.5, 24.4, and 129.1 ng/ml, respectively, at 3.1, 4.2, and 4.5 h; after the 40-mg sustained-release formulation, they were 10.9, 44.0, and 214.5 ng/ml, respectively, at 4.2, 6.3, and 6.7 h; and after the 20-mg standard formulation, they were 19.1, 34.7, and 159.2 ng/ml, respectively, at 0.5, 1.0, and 1.5 h. As might be expected, peak concentrations and their times of occurrence were statistically significantly different when results from the sustained-release formulation were compared to those from the standard formulation. Plasma drug concentrations were detectable for longer after administration of the sustained-release formulations. The extent of bioavailability of ISDN, 2-ISMN, and 5-ISMN from the three formulations as estimated from the areas under the plasma drug concentration - time curves were not statistically significantly different (p greater than 0.05). The ratios for relative drug bioavailability from the respective formulations were similar whether ISDN, 2-ISMN, or 5-ISMN data were used for calculation. Reasons are discussed for the biphasic decline of plasma ISDN concentrations (half-lives 26 min and 5.1 h) obtained after administration of the standard-release formulation.

Adolescent↗
PubMed1983

[Pharmacokinetics of 14C-isosorbide dinitrate after administration in various sustained-release formulations].

To study the influence of various in vitro release rates and of coadministration with food on bioavailability of isosorbide dinitrate (ISDN; isoket retard 40) and its mononitrate metabolites from sustained-release formulations the pharmacokinetics of two experimental batches of tablets with different release rates containing 40 mg 14C-ISDN each were studied in six human volunteers. One of the formulations was not only administered after fasting but aslo with a standard meal. In all cases approx. 80% of the administered radioactivity were recovered in the urine and 5% in the faeces during 3 days demonstrating extensive absorption. Any influence of release rates or food on absorption rates could not be detected. When administered after fasting either formulation was bioequivalent. Coadministration of a meal enhanced ISDN plasma levels in some subjects although no statistically significant difference in extent of bioavailability was observed. Availability of the mononitrates was unaffected by food.

Adult↗
PubMed1982

Etretinate in treatment of actinic keratosis. A double-blind crossover study.

50 patients with actinic keratosis were studied over four months of treatment with either etretinate ('Tigason') or placebo. Each treatment was given for two months and the order of administration was randomised. The clinical response to treatment was assessed by direct measurement and photographs of the lesions at monthly intervals. Of the 44 patients who completed treatment with etretinate 37 had a complete or partial response. Of the 42 patients who completed treatment on placebo only 2 showed a complete or partial response. The response to treatment occurred within the first month of therapy and was maintained even when the dose was reduced because of toxicity.

Aged↗
PubMed1982

Endocrine response patterns and psychological correlates.

A group of young men volunteering for military service in the United States Navy were studied during an acute stress situation. The subjects (S's)(N = 62) were non-swimmers, and they all had to jump from a 5-foot platform into the deep end of a swimming pool. Before and after the exposure, blood and urine samples were taken for endocrine analysis. The Defense Mechanism Test (DMT), the Coping Operations Preference Enquiry (COPE), Joffe and Nanitch Scales for Defenses (J&N), and a Mood Questionnaire (MQ) were administered. For the endocrine reactions, postsamples, 3 factors emerged: a Cortisol factor, a Testosterone factor, and a Catecholamine factor. There was a significant correlation between the Cortisol factor and defense mechanisms, evaluated both by the DMT and the paper-and-pencil tests. Furthermore, there was a significant relationship between high anxiety, and defense mechanisms on the one hand, and physiological responses on the other.

Adaptation, Psychological↗
PubMed1982

RO 15-1788 antagonises the central effects of diazepam in man without altering diazepam bioavailability.

1 In a double-blind, placebo controlled study, the efficacy of Ro 15-1788, a new benzodiazepine antagonist, in blocking the cognitive, psychomotor and subjective effects of diazepam, was investigated in a group of six healthy male volunteers. 2 The central effects of orally administered diazepam (40 mg) were most pronounced 1 h after dosing and persisted for 9 h with decreasing severity. 3 Concurrent oral administration of Ro 15-1788 (200 mg) completely prevented the impairment in cognitive and psychomotor function observed after diazepam alone. 4 The duration of action of Ro 15-1788 was shorter than that of diazepam. 5 Plasma diazepam levels after administration of the diazepam/antagonist combination were very similar to those observed following diazepam alone.

Adult↗
PubMed1982

The metabolism of the hypolipidaemic drug sultosilic acid in rat, dog and man.

1. Single oral doses of the hypolipidaemic drug [35S]sultosilic acid to rats (40 mg/kg), dogs (40 mg/kg) and man (7 mg/kg) were well absorbed. During three days, means of 59.2%, 58.8% and 61.8% in urine and 37.7%, 31.9% and 19.7% in faeces, were excreted by these species respectively. Most of the dose was excreted during the first 24 h. 2. Peak plasma levels of 35S were generally reached during 1-2 h after oral doses in rats (12 micrograms equiv./ml), dogs (45 micrograms equiv./ml) and two human subjects (15.2 and 10.3 micrograms equiv./ml). In humans, peak plasma levels of unchanged drug (at 1-1.5 h) were 10.5 and 6.3 micrograms/ml. Plasma concentrations of 35S increased almost proportionately to dose in rats following oral doses of 400 and 1200 mg/kg, although in dogs, concentrations were similar at these two dose levels but several times higher than at 40 mg/kg. 3. Tissue concn. of 35S were generally higher in rats than in dogs. Highest concn. occurred at 3 h in rats and 1 h in dogs. Apart from those in the liver and kidneys, tissue concn. were appreciably lower than the corresponding plasma levels. 4. The major radioactive component in dog urine was sultosilic acid. Rat and human urine contained sultosilic acid and also two more polar major metabolites. In male and female rat urine, the proportions of these excretory products differed and the proportions in male rat urine were similar to those in human urine. Sultosilic acid was also the only component detected in dog plasma, whereas rat and human plasma also contained the two urine metabolites. Dog bile contained a conjugate of sultosilic acid. 5. The two metabolites have been identified by mass spectrometry and nuclear magnetic resonance spectroscopy as products resulting from oxidation of the methyl in the p-toluenesulphonyl group. The structures assigned are the corresponding carboxylic acid and the hydroxymethyl derivatives.

Administration, Oral↗
PubMed1981

The effect of multiple rising doses of Ro 11-2465 (serotonin uptake inhibitor) on serotonin content of human platelets.

Ro 11-2465, a cyanide derivative of imipramine with serotonin uptake inhibitory properties, was investigated in six healthy volunteers for its effect on serotonin concentration in blood platelets. The initial dose was 1 mg daily, the maximum dose of 3 mg being reached on day 3 and maintained for 7 days. A significant decrease in the platelet serotonin concentration was not observed until 3 days after the start of drug administration, after which depletion was rapid. After 5 days of treatment, the reduction was about 80% compared to pre-drug level. Serotonin restoration after drug withdrawal was very slow, and 5 days after discontinuation, it was still 70% below its baseline level.

Blood Platelets↗
PubMed1981

Prolactin responsiveness to repeated decremental doses of sulpiride.

The variation in the prolactin response to sulpiride was studied in six normal men by repeating the same dose of the drug (50 mg) after 24 hours and on three subsequent occasions, repeating this 2 day test at an interval of 6 days with progressively halved doses of sulpiride. A similar PRL response occurred on the first day of each test period and the peak response was highly significant (P less than 0.001), occurring within 30 minutes. A gross blunting of the PRL response on the second day of each period was noted throughout the study. The difference in delta PRL between the first and second day of each period was highly significant (P less than 0.001). The delta PRL increment on the second day was inversely proportional to the dose of sulpiride; the differences in delta PRL between periods 1 and 3 and periods 1 and 4 being highly significant (P less than 0.001). This study suggests that a much lower dose of sulpiride than that normally used is adequate to stimulate PRL secretion and that care must be taken in the timing of repeat testing.

Adult↗
PubMed1981

The metabolic fate of 3[H]econazole in man.

1. Following single oral doses of 3[H]econazole base (500 mg) to two human subjects, excretion of radioactivity was prolonged, and incomplete after five days (means of 40% and 27% dose in urine and faeces respectively). 2. Plasma concn. of unchanged econazole and total radioactivity attained peak values at approx. the same for each subject (1.5 - 3h), but the former declined much faster than the latter. Most of the 3H in early plasma samples was present as unchanged drug and extractable metabolites, but after 24h concn. of econazole were close to the limit of detection (0.04 ug/ml) and very little plasma 3H was extractable, whereas total 3H concn. were still measurable after five days (mean 1.54 ug/ml). Thus, plasma contained metabolites with much longer half-lives than econazole. 3. The main route of biotransformation of econazole in man involved multiple oxidation of the imidazole ring carbons followed by O-dealkylation and conjugation of the resulting alcohols, probably with glucuronic acid.

Administration, Oral↗