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Biomedical subjects

A Darragh

Publications and source records attributed to A Darragh.

At least 73 records · Page 4Linked to original sources
PubMed1981

Effects of Ro 11-2465, a new psychotropic agent on the uptake of serotonin by human platelets--in vitro determination of the IC50.

The influence of Ro 11-2465, a new psychotropic agent, on the in vitro uptake of 3H-serotonin into human blood platelets was studied and compared with that of clomipramine, imipramine and amitriptyline. These compounds inhibited the uptake of serotonin in a dose-dependent manner. Ro 11-2465 was found to be six times more potent than clomipramine and 14 times more potent than imipramine in its ability to inhibit serotonin uptake. IC50 value determined for Ro 11-2465 was 7 x 10(-10) M. The results indicate the potential ability of Ro 11-2465 to interfere with the human serotoninergic mechanism.

Antidepressive Agents↗
PubMed1980

Determination of the antispasmodic agent ethaverine in human plasma by high-performance liquid chromatography.

Ethaverine can be measured in the plasma of human subjects by reversed-phase high-performance liquid chromatography employing UV detection. The limit of detection was 2 ng/ml, and the precision was +/- 14, +/- 6 and +/- 2% at concentrations of 5, 25 and 50 ng/ml respectively. A peak mean plasma drug concentration of 20 ng/ml occurred at 1.5 h after single oral doses of a capsule formulation to human subjects, and declined with a half-life of 2.9 h.

Administration, Oral↗
PubMed1980

The absorption and excretion of the peripheral vasodilator 14C-mecinarone, (14C-6809 MD) in rat, dog and man.

Oral doses of the peripheral vasodilator mecinarone (6809 MD), administered as the 14C-compound, were well absorbed from the gastrointestinal tract of rats, dogs and humans. Much of the dose was excreted in 24 by rats and dogs, but more slowly by humans. In 5 days, rats, dogs and humans excreted in the urine and faeces respectively means of 3.3 and 95.9%, 13.2 and 80.3%, and 22.0 and 60.8%. The proportions of radioactivity excreted in urine and faeces after intravenous doses were similar to those after oral doses, means of 3.1 and 85.0% respectively by rats and 16.8 and 78.3% by dogs. Radioactivity present in the faeces was probably mainly excreted in bile; rats (n = 2) excreted a mean of 52.3, 19.8 and 3.9% in bile, faeces and urine after oral doses. Plasma concentrations of radioactivity after oral doses reached a maximum at 1 h in rats (mean 126 ng equiv/ml), at 1 to 2 h in dogs (mean 784 ng equiv/ml) and at 1.5 to 2 h in humans (mean 547 ng equiv/ml. Only a small proportion of this radioactivity (10-30%) represented unchanged drug. When "normalised" for dose/bodyweight differences, those levels were in the ratio 1 : 7 : 32 (rat less than dog less than man). Areas under plasma radioactivity concentration-time curves after oral doses to rats and dogs were about 25% and 53% respectively of those after corresponding intravenous doses. Only about 20% of the radioactivity in the plasma of dogs at 2 min after an intravenous dose represented unchanged drug. These data suggest that 6890 MD was probably rapidly biotransformed in rat, dog and man.

Administration, Oral↗
PubMed1980

Sleep-endocrine profile of the antidepressant mianserin.

The effects of mianserin, a tetracyclic antidepressant, on sleep stages and on the nocturnal secretion of cortisol, ACTH, growth hormone, prolactin and tryptophan were studied on 11 normal male volunteers in a double-blind, placebo-controlled study. Mianserin increased Stage 3 time (p less than 0.001) and Stage 4 time (p less than 0.01). It reduced the number of REM periods (p less than 0.001), the REM latency after sleep onset (p less than 0.01) and both the total and percentage REM time (p less than 0.05). A reduction in both the total sleep time (p less than 0.05) and the percentage of total time in bed (p less than 0.05) were the only significantly carry-over effects from the drug treatment period. No significant difference in any biochemical measurement was found between placebo and drug treatment.

Adult↗
PubMed1980

The metabolic fate of Sormodren (bornaprine hydrochloride) in animals and humans.

1. Single oral doses of the anticholinergic drug [14C]Sormodren to rats (1 mg/kg), dogs (0.3 mg/kg) and humans (0.03 mg/kg) were well absorbed. Excreted in urine and faeces were means of 31 and 70%, 53 and 39%, and 78 and 4% in rats, dogs, and humans, respectively, during five days: excretion was prolonged and still incomplete at five days in humans. 2. Peak plasma levels of 14C (scaled for dose) were generally reached within 1-2 h after oral doses in rats, 49 (ng/ml)/(mg/kg), dogs 290 (ng/ml)/(mg/kg) and humans 410 (ng/ml)/(mg/kg), and declined with half-lives of approx. 5, 12 and 30 h, in these species respectively. Repeated oral doses of [14C]Sormodren to dogs resulted in some accumulation of 14C in the plasma. 3. Tissue concn. of 14C in dogs were generally higher than those in rats, particularly in the brain, lungs and eyes. The tissue distribution of 14C in rats and dogs was consistent with that of a compound readily eliminated by both renal and hepatic routes. 4. Basic metabolites in dog and human, urine and plasma were investigated using a combination of h.p.l.c. and g.l.c.-mass spectrometry. Unchanged Sormodren was not detected in the dog samples and was only a minor component in human urine and plasma. Some metabolites were present as conjugates. 5. A basic extract of enzyme-hydrolysed dog urine (5 mg/kg dose) contained 42% of the urine 14C. The major metabolites in this fraction were identified as three isomers of monohydroxy-N-desethyl-Sormodren and three isomers of monohydroxy-Sormodren, resulting from hydroxylation in the bicyclic ring. The positions of oxidation were not determined. A similar extract from dog urine (0.3 mg/kg dose) contained 26% of the urine 14C and the major metabolites were identified as isomers of monohydroxy-N-desethyl-Sormodren. 6. A basic extract of enzyme-hydrolysed human urine (0.03 mg/kg dose) contained 23% of the urine 14C. The unchanged drug was only a minor component and most of the radioactivity was associated with five isomers of monohydroxy-Sormodren, hydroxylation having occurred in the bicyclic ring. 7. Basic extracts of dog and human plasma only contained about 10% of the plasma 14C. Metabolites were chromatographically similar to the hydroxylated metabolites identified in the corresponding urine samples.

Adult↗
PubMed1979

High-performance liquid chromatographic determination of the nitroimidazole azanidazole in human plasma and urine.

Azanidazole can be measured in plasma and urine by reversed-phase high-performance liquid chromatography employing UV detection. Peak mean plasma concentrations of azanidazole, of 267 ng/ml, occurred at 1.5 h after single oral doses to human subjects, and declined with a half-life of 0.8 h. Less than 0.5% of the dose was excreted in the urine as unchanged drug. Metabolites of azanidazole were also detected by the procedures used.

Chromatography, High Pressure Liquid↗
PubMed1979

Effect of beta-blockers on exercise double product (systolic blood pressure x heart rate).

1 The effect of single oral doses of six beta-receptor antagonists on exercise-induced changes in double product (systolic blood pressure x heart rate) were studied in 25 human volunteers. 2 Three doses of propranolol, nadolol, oxprenolol, pindolol, timolol and atenolol were selected for study on the basis of in vivo beta-blocking potency. 3 Although all beta-blockers studied reduced the double product response to exercise, the pharmacodynamics of this effect differed markedly. 4 Pharmacodynamic half-lives, estimated for the drug tested, were 39 h for nadolol, atenolol 21 h, timolol 15 h, oxprenolol 13 h, propranolol 11 and pindolol 8 h. 5 These results suggest that the clinical choice of a beta-blocker with the least problems of compliance can be made on the basis of pharmacodynamics as well as pharmacological profile.

Adolescent↗
PubMed1979

Chronic dopamine receptor stimulation using bromocriptine: failure to modify thyroid function.

Administration of 2.5 mg bromocriptine (Parlodel), a dopamine agonist, on two occasions to six normal volunteers did not alter the plasma TSH response to an i.v. injection of 100 micrograms TRH, but significantly (P less than 0.01) blunted it after 200 micrograms. Chronic bromocriptine treatment (7.5--50 mg/day) of fifteen acromegalic subjects failed to influence basal plasma TSH or the response pattern to 200 micrograms TRH. The thyroxine Binding Index (TBI) and the levels of T3 and T4 were not modified by treatment. These results indicate that chronic dopaminergic therapy with bromocriptine does not alter thyroid function.

Acromegaly↗
PubMed1978

Pharmacokinetics of flunitrazepam following single- and multiple-dose oral administration to healthy human subjects.

Healthy human subjects received single and multiple oral doses of flunitrazepam. Absorption and disposition were first order and reproducible from administration. The oral doses were virtually completely available to the liver, and elimination from the body occurred entirely via metabolism. Assuming the liver to be the sole eliminating organ, hepatic blood clearance and extraction ratio were approximately 0.235 liter/hr/kg and 0.154, respectively. Steady-state blood volume of distribution averaged 3.76 liters/kg in the single-dose studies. Terminal exponential half-lives from the single- and multiple-dose studies (different subjects) averaged 13.5 and 19.2 hr, respectively; these differences were not due to clearance changes but were entirely attributable to variations in volumes of distribution.

Administration, Oral↗