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M L Selley

Publications and source records attributed to M L Selley.

22 records · Page 2Linked to original sources

Pharmacokinetic studies of tolmetin in man.

The pharmacokinetics of the new anti-inflammatory agent tolmetin have been studied after its oral administration to normal subjects and to patients with rheumatoid arthritis. Plasma concentration-time data were fitted to a one-compartment open model. Following single oral doses, no basic differences in rates of drug absorption and elimination were found between normal subjects and arthritic patients. For the 12 subjects studied, the overall mean elimination rate constant was 0.839 hr-1, corresponding to a plasma half-life of 0.83 hr. The drug was rapidly absorbed and had a mean apparent volume of distribution of 0.098 l/kg. Plasma levels and pharmacokinetic parameters of tolmetin in arthritic patients after multiple dosing were smaller to those after a single dose.

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The effect of increased concentrations of homocysteine on the concentration of (E)-4-hydroxy-2-nonenal in the plasma and cerebrospinal fluid of patients with Alzheimer's disease.

There is evidence that increased blood concentrations of homocysteine may be a risk factor for Alzheimer's disease. (E)-4-hydroxy-2-nonenal (HNE) is a neurotoxic product of lipid peroxidation that is increased in the ventricular fluid and brains of patients with Alzheimer's disease. We measured the concentrations of homocysteine, HNE, vitamin B(12) and folate in the plasma of 27 patients with Alzheimer's disease and 25 control subjects. There was a statistically significant increase in the plasma concentration of homocysteine (P < 0.001) and HNE (P < 0.001) in the Alzheimer's disease patients compared to the control group. There was a significant decrease in the plasma concentration of vitamin B(12) (P < 0.001) and folate (P = 0.002) in the Alzheimer's group compared to the controls. There was a significant positive correlation between the plasma concentrations of homocysteine and HNE in the patients with Alzheimer's disease (r = 0.661, P < 0.001). A significant negative correlation was found between the plasma concentration of homocysteine and the plasma concentrations of vitamin B(12) (r = -0.605, P = 0.0006) and folate (r = 0.586, P = 0.001). We also measured the concentrations of homocysteine, HNE, vitamin B(12) and folate in the cerebrospinal fluid (CSF) of 8 patients with Alzheimer's disease compared to 6 control subjects. The concentrations of homocysteine (P = 0.032) and HNE (P = 0.001) were significantly higher in the CSF of Alzheimer's patients than in the control subjects. There were significant positive correlations between the CSF concentrations of homocysteine and HNE (r = 0.924, P = 0.001). There was also a significant positive correlation between the plasma concentration of homocysteine and the CSF concentrations of homocysteine (r = 0.850, P = 0.007) and HNE (r = 0.092, P = 0.002). These results demonstrate that there is a relationship between increased homocysteine concentrations and increased HNE concentrations in Alzheimer's disease.

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