PubMed Health⌕ Search

Biomedical subjects

T K Holland

Publications and source records attributed to T K Holland.

9 recordsLinked to original sources
PubMed1997

Pharmacokinetics, absorption, distribution and disposition of [125I]-oligotide following intravenous or oral administration in the rat.

Oligotide (O) was labelled with 125I. The radiolabelled compound ([125I]-Oligotide ([125I]-O)) retained the biological activity of parent O. Following single intravenous administration the half lives of radioactivity associated with O and/or O related components in plasma were 9-10 min and 9-10 h for alpha and beta phases respectively. Following single oral administration the half life of radioactivity associated with O and/or O related components in plasma was 11.45-12.76 h for beta fase. Following multiple oral administration once daily for 7 days, the half life of radioactivity associated with O and/or O related components following the 7th dose was 10-12 h for beta phase. The areas under plasma total radioactivity versus time curves were dose-dependent. Following single intravenous administration the major proportion of the administered dose was excreted via urine, while following single oral administration excretion via urine and faeces accounted for similar proportions of the administered dose. Following both single and oral administration the levels of radioactive components derived from [125I]-O in organs examined were generally highest in highly perfused organs.

Absorption↗
PubMed1996

Study on pharmacokinetics of radioactive labelled defibrotide after oral or intravenous administration in rats.

Defibrotide (D) was labelled with 125I or with 32P. The radiolabelled compounds ([125I]-Defibrotide ([125I]-D), [32P]-Defibrotide ([32P]-D) retained the same profibrinolytic activity, in vitro, as the parent drug, suggesting that the labelling procedures had not modified the pharmacological properties of D and hence that its chemical structure was not affected significantly. After single intravenous or oral administration of [125I]-D or [32P]-D the pharmacokinetic parameters for the two labels were generally in good agreement (75%). t 1/2 alpha was in the range of minutes while t 1/2 beta was in the range of hours. Bioavailability, following single oral administration of [125I]-D or [32P]-D, was in the range of 58-70%. These data suggest that D, in spite of its macromolecular nature, is absorbed, after oral administration, fairly well.

Administration, Oral↗
PubMed1993

Pharmacokinetics, absorption, distribution and disposition of [125I]-defibrotide following intravenous or oral administration in the rat.

Defibrotide (D) was labelled with 125I. The radiolabelled compound ([125I]-Defibrotide ([125I]-D)) retained the same profibrinolytic activity as the parent drug. Following single intravenous administration of [125I]-D the half lives of radioactivity associated with D components in plasma were 9.45 min and 11.27 h for alpha and beta phases respectively. Following single oral administration of [125I]-D the half life of radioactivity associated with D components in plasma was 12.83 h for the elimination phase. Bioavailability was apparently 58%. The areas under plasma total radioactivity versus time curves were dose-dependent following both intravenous and oral administration. No significant accumulation of total radioactivity in plasma was observed following multiple oral administration of [125I]-D. Following single intravenous administration of [125I]-D a larger proportion of administered radioactivity was excreted via urine than faeces while following single oral administration excretion via urine and faeces accounted for similar proportions of administered radioactivity. Following both single and oral administration the levels of total radioactivity in tissues and organs examined were generally highest in highly perfused organs and were very high in the thyroid despite pretreatment with non-radiolabelled potassium iodide. Radioactivity was also found to be associated with the aorta wall.

Absorption↗
PubMed1989

Evaluation of the effect of cicletanine on genetic atherosclerosis in the rabbit.

This study was designed to evaluate the hypolipidaemic and anti-atherosclerotic potential of cicletanine in a genetic hypercholesterolaemic rabbit model. In a pilot study the effect of 8 weeks oral administration of 2 treatment levels of cicletanine (10, 30 mg.kg-1.day-1) was compared with vehicle alone. In the main study, 8 weeks oral administration of 2 treatment levels of cicletanine (5, 30 mg.kg-1.day-1) was compared with parallel treatment with probucol (15 mg.kg-1.day-1) and with nifedipine (10 mg.kg-1.day-1). At the start of each study and at scheduled points throughout, blood samples were collected for routine biochemical and lipid/lipoprotein analyses. At the end of each test period all animals were examined at post mortem. Aortae were dissected and examined for the presence ans degree of atheroma. Hearts were examined for the presence of lesions. Sections of aortae were stained for lipid, examined histologically and scored for extent of atheroma using an atherosclerotic index. In the pilot study cicletanine had no effect on blood lipid levels. Gross pathology indicated a reduction in the extent of aortic atheroma in cicletanine-treated animals. Histopathological examination of thoracic and abdominal regions of the aortae confirmed these gross findings. The atherosclerotic index was significantly reduced (p less than 0.06) in all drug treated animals. In the main study similar data were achieved. None of the test drug affected plasma lipid/lipoprotein levels. Gross pathology indicated a reduction in the extent of aortic atheroma in all cicletanine-treated animals and also in the nifedipine-treated group. This was confirmed by histopathological examination of thoracic and abdominal regions of the aortae.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1980

The interrelationship between thromboxane biosynthesis, aggregation and 5-hydroxytryptamine secretion in human platelets in vitro.

Platelet aggregation, secretion of 5-hydroxy tryptamine and production of thromboxane B2 were monitored simultaneously in human platelet suspensions in the absence and presence of cyclooxygenase or thromboxane synthetase inhibitors. Aggregation, secretion and thromboxane B2 formation in response to either sodium arachidonate or epinephrine were blocked by aspirin or by 1-N-butyl inidazole suggesting that thromboxane biosynthesis was an essential requirement for platelet activation by these agents. In contrast, thrombin and collagen could apparently induce aggregation and secretion via two pathways: at low doses involving thromboxane production, but at higher doses by a direct mechanism independent of thromboxane biosynthesis. In the case of ADP, inhibition of thromboxane production blocked secretion but had little effect on aggregation, indicating that secretion was probably dependent on thromboxane biosynthesis which probably occurred as a result of aggregation. Thus it appears that although the processes of thromboxane production, release of dense granule constituents and aggregation may often be intimately linked, each process can occur independently of the other, depending upon the stimulus used.

Blood Platelets↗