PubMed Health⌕ Search

Biomedical subjects

G Edwards

Publications and source records attributed to G Edwards.

At least 73 records · Page 4Linked to original sources
PubMed1990

The action of diazoxide and minoxidil sulphate on rat blood vessels: a comparison with cromakalim.

1. The actions of diazoxide and minoxidil sulphate have been compared with those of cromakalim in rat aorta and portal vein. 2. Diazoxide and minoxidil sulphate hyperpolarized the rat portal vein in a similar manner to cromakalim. 3. Cromakalim, diazoxide and minoxidil sulphate increased 42K and 86Rb efflux from rat portal vein, although minoxidil sulphate had only a small effect on 86Rb efflux. 4. Cromakalim, diazoxide and minoxidil sulphate increased 42K efflux from rat aorta but only cromakalim and diazoxide increased 86Rb efflux from this tissue. 5. Glibenclamide inhibited the relaxant actions of cromakalim, diazoxide and minoxidil sulphate on rat aorta and the increase in 42K efflux produced by these agents in this tissue. 6. Diazoxide relaxed an 80 mM KCl-induced contraction of rat aorta, whilst cromakalim and minoxidil sulphate were without effect. 7. Cromakalim, diazoxide and minoxidil sulphate had no effect on cyclic AMP or cyclic GMP concentrations in rat aorta. 8. It is concluded that diazoxide and minoxidil sulphate like cromakalim exhibit K+ channel opening properties in vascular smooth muscle. Diazoxide exerts an additional inhibitory action not related to the production of cyclic AMP or cyclic GMP. The action of minoxidil sulphate may be primarily located at a K+ channel which is relatively impermeable to 86Rb.

Animals↗
PubMed1990

Flurbiprofen in human crevicular fluid analyzed by high-performance liquid chromatography.

The aim of this study was to determine whether the non-steroidal anti-inflammatory drug, flurbiprofen, which has been shown to be an inhibitor of alveolar bone loss in human periodontal disease, is present in human crevicular fluid (CF) following oral dosing. A method is described whereby routine high-performance liquid chromatography is used to detect the drug in only 20 microliters of CF. 5 volunteers abstained from toothbrushing for 21 days to induce experimental gingivitis and increase the resting flow of CF. 100 mg of flurbiprofen was taken by each volunteer on d 21-28. On d 21 and 28, serum and CF samples were taken prior to dosing and afterwards at 1, 2, 4 and 6 hours. On d 21 the mean peak concentration of the drug in serum was about 11 micrograms/ml and was found between 1-2 h after dosing. The respective values for CF (d 21) were 0.32 micrograms/ml and 4 h. On d 28 flurbiprofen was detected in both fluids prior to dosing. The mean peak concentrations after dosing had increased to 13.13 micrograms/ml (serum) and 0.46 micrograms/ml (CF) although the levels of the drug in CF remained relatively constant throughout the observation period on d 28. The results indicate that flurbiprofen may be detected in human CF after oral administration and that the levels are in excess of the plasma level, which in beagles has been shown to inhibit alveolar bone loss in periodontal disease.

Administration, Oral↗
PubMed1990

The effect of malaria infection on the disposition of quinine and quinidine in the rat isolated perfused liver preparation.

The effect of malaria on the disposition of quinine and quinidine was studied in livers isolated from young rats infected with merozoites of Plasmodium berghei, a rodent malaria model, and non-infected controls. Following bolus administration of quinine (1 mg) or quinidine (1 mg) to the 100 mL recycling perfusion circuit, perfusate was sampled (0-4 h) and plasma assayed for quinine and quinidine by HPLC. Higher quinine (AUC:6470 +/- 1101 vs 3822 +/- 347 ng h mL-1, P less than 0.001) and quinidine (AUC: 6642 +/- 1304 vs 4808 +/- 872 ng h mL-1, P less than 0.05) concentrations were observed during malaria infection (MI). MI resulted in decreased quinine clearance (CL) (0.33 +/- 0.08 vs 0.64 +/- 0.09 mL min-1 g-1, P less than 0.001) and volume of distribution (Vd) (53.0 +/- 13.3 vs 81.2 +/- 23.7 mL g-1, P less than 0.05) but no significant change in elimination half-life (t1/2) (1.93 +/- 0.6 vs 1.37 +/- 0.25 h, P greater than 0.05). With quinidine, however, MI resulted in decreased CL (0.38 +/- 0.16 vs 0.64 +/- 0.09, P less than 0.05) with no change in Vd and a significant increase in t1/2 (1.62 +/- 0.42 vs 0.88 +/- 0.22, P less than 0.01). In summary, the hepatic disposition of quinine and quinidine is altered in the malaria-infected rat.

Animals↗
PubMed1990

The potassium channel openers: a new class of vasorelaxants.

Cromakalim, pinacidil, nicorandil, diazoxide and RP-49356 belong to the class of drugs termed potassium channel openers. In rat portal vein diazoxide, like cromakalim, abolished spontaneous mechanical and electrical activity and in rat aorta caused an increase in 86Rb efflux and inhibited KCl(20 mM)-induced contractions. However, in contrast to cromakalim, diazoxide (greater than 100 microM) also inhibited mechanical responses evoked by 80 mM KCl in rat aorta suggesting that it possesses pharmacological properties in addition to K channel opening. Since glibenclamide can attenuate the effects of cromakalim and diazoxide in vascular tissues, it is possible that a channel resembling the ATP-sensitive K channel found in pancreatic beta-cells may be involved in the vasorelaxant effects of these agents. However, differences exist in the order of potency of cromakalim and diazoxide for producing smooth muscle relaxation and for decreasing insulin secretion in pancreatic beta-cells. Furthermore galanin (which opens ATP-sensitive K channels in beta-cells) increases mechanical activity in rat portal vein. It is anticipated that new chemical developments will produce K channel opening molecules with greater potency and tissue selectivity.

Animals↗
PubMed1990

The chemotherapy of onchocerciasis. XIV. Studies with mebendazole citrate.

Twenty patients from an area of vector control in the savannah region of northern Ghana with moderate to heavy infection with Onchocerca volvulus were randomised to receive two priming doses of levamisole 150 mg on two occasions followed either by mebendazole-citrate (500 mg) given daily or twice daily for 14 days. The two dose levels produced a similar effect on skin microfilariae (80-88% reduction) with a very mild systemic clinical reaction: low levels were maintained over 42 weeks. Both regimes were embryotoxic for O. volvulus; an effect which was transient in the single dose group but persisted for more than three months in the twice daily dose group. Mebendazole-citrate appeared to be absorbed more predictably than has been observed previously for mebendazole. The degree of systemic exposure as determined by measurement of AUC (0-24 h) was 2.5 times greater for the twice daily dose as compared to the single dose and this fact was reflected in the efficacy of the two dose regimes against the adult female worms at three months.

Adult↗
PubMed1989

Determination of artelinic acid in blood plasma by high-performance liquid chromatography.

A reversed-phase high-performance liquid chromatographic method is described for the analysis of the new antimalarial drug artelinic acid in blood plasma. The influence of mobile phase composition, pH and type of mobile phase modifier on the retention of artelinic acid on the reversed-phase column is reported. Linear calibration curves were obtained in the range 0-500 ng/ml artelinic acid. Intra-assay and inter-assay variability in the analysis of plasma samples spiked with the drug were less than or equal to 15%. Plasma samples of the drug were found to be unstable when stored at -20 degrees C, the concentration of the drug decreasing by over 50% within three days. Plasma samples stored at -70 degrees C remained stable for at least two weeks. Initial pharmacokinetic studies in the rat showed that following intravenous administration, plasma concentrations of artelinic acid declined mono-exponentially. The relatively short elimination half-life (17 +/- 5 min) of artelinic acid is consistent with what is known for qinghaosu and its derivatives.

Animals↗
PubMed1989

Determination of arteether in blood plasma by high-performance liquid chromatography with ultraviolet detection after hydrolysis acid.

A reversed-phase high-performance liquid chromatographic method is described for determination of the antimalarial agent arteether in blood plasma based on its decomposition in acidic medium and measurement of the major decomposition product, which has been identified as an alpha,beta-unsaturated decalone. Linear calibration curves were obtained in the range 0-250 ng/ml arteether and the recovery of the drug from plasma was found to be quantitative. There is no interference from desoxyarteether, the putative major metabolite of arteether. The method has been applied to the measurement of arteether in the plasma of rats given 110 mg/kg by intramuscular injection of the drug as a solution in sunflower oil.

Animals↗
PubMed1989

Blasted with ennui.

Explore the source record for details and available documents.

3,4-Methylenedioxyamphetamine↗
PubMed1989

Avascular necrosis of bone in bone marrow transplant patients.

Avascular necrosis of the hips occurred in two patients after allogeneic bone marrow transplantation. One had been receiving steroid therapy for prophylaxis of graft-versus-host disease, the other for the treatment of this condition. This complication has been reported infrequently, but the incidence could be as high as 10% in long-term survivors of bone marrow transplantation. While other drugs and irradiation may also contribute to this condition, it is likely that steroids are the major cause. An awareness of this risk should encourage minimizing the use of steroid therapy after bone marrow transplantation.

Adrenal Cortex Hormones↗
PubMed1989

What drives British drug policies?

This paper identifies four broad types of influence which have contributed to the dynamics of British drug policy development over many decades: international influences, varieties of fear, professional entrepreneurship, and the perceived tension between treatment and control. A follow-through of these same themes to current policy concerns is traced. The need to develop a comparative and international framework for policy analysis is stressed. Policy research, it is argued, deserves to be given greater attention as the necessary means toward a more informed sense of feasibilities and policy options.

Health Policy↗
PubMed1989

Pharmacokinetics of halofantrine in man: effects of food and dose size.

1. Plasma concentrations of halofantrine (Hf) and its putative principal plasma metabolite desbutyl halofantrine (Hfm) have been measured in two separate studies after oral administration of the hydrochloride salt. 2. Six healthy male volunteers each received single oral doses of 250, 500 and 1000 mg administered after an overnight fast. A washout period of at least 6 weeks was allowed between each dose. A further 250 mg single oral dose was administered to the same six subjects in a fasting state and after a standardised fatty meal in a randomised study, again with a washout period of at least 6 weeks. 3. AUC and maximum plasma concentration (Cmax) for Hf increased in proportion to the dose from 250-500 mg. This increase was non-proportional when the dose was increased from 500 to 1000 mg. For Hfm, in the dose range 250-500 mg, AUC but not Cmax increased in proportion in the increase in dose size. The increase in these parameters was non-proportional when the dose was increased from 500 to 1000 mg. Time to reach peak concentrations for Hf and Hfm and the elimination half-life of Hf remained unchanged across the dosage range. 4. Following a fatty meal, Cmax for Hf was increased from 184 +/- 115 micrograms l-1 (fasting) to 1218 +/- 464 micrograms l-1 (fed). AUC for Hf was increased from 3.9 +/- 2.6 mg l-1 h (fasting) to 11.3 +/- 3.5 mg l-1 h following a fatty meal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

An improved formulation of chloroquine for intramuscular administration: absorption kinetics in rabbits.

Intramuscular chloroquine is rapidly absorbed, even in severe falciparum malaria, and may cause potentially lethal hypotension. Less rapidly absorbed formulations should be safer. A chloroquine phosphate solution containing 2% methylcellulose 1500 released chloroquine 2.6 times more slowly than a commercial aqueous solution in an in-vitro absorption simulator. There was a log linear relationship between viscosity and release rate. The absorption pharmacokinetics of the more viscous chloroquine phosphate solution were then compared with those of a commercial solution after intramuscular injection to eight rabbits in an open cross over comparison. The rate of absorption was over three times slower with the viscous solution; median time to peak whole blood concentration with the commercial aqueous solution was 10 (range 5-20) min compared with 30 (range 10-60) min for the more viscous formulation (P less than 0.05). Peak whole blood concentrations were 66% (95% CI 50-82%) of those with the commercial preparation, but the acute bioavailability of the two solutions was similar. This simple new formulation may be safer than currently available chloroquine preparations and should now be evaluated in man.

Absorption↗