Search PubMed⌕ Search

Biomedical subjects

G Edwards

Publications and source records attributed to G Edwards.

414 records · Page 23Linked to original sources
PubMedDate not supplied

Pharmacokinetics of phenytoin following intravenous and intramuscular administration of fosphenytoin and phenytoin sodium in the rabbit.

The purpose of this study was to evaluate and compare plasma phenytoin concentration versus time profiles following intravenous (i.v.) and intramuscular (i.m.) administration of fosphenytoin sodium with those obtained following administration of standard phenytoin sodium injection in the rabbit. Twenty-four adult New Zealand White rabbits (2.1 +/- 0.4 kg) were anaesthetized with sodium pentobarbitone (30 mg/kg) followed by i.v. or i.m. administration of a single 10 mg/kg phenytoin sodium or fosphenytoin sodium equivalents. Blood samples (1.5 ml) were obtained from a femoral artery cannula predose and at 1, 3, 5, 7, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240 and 300 min after drug administration. Plasma was separated by centrifugation (1000 g; 5 min) and fosphenytoin, total and free plasma phenytoin concentrations were measured using high performance liquid chromatography (HPLC). Following i.v. administration of fosphenytoin sodium plasma phenytoin concentrations were similar to those obtained following i.v. administration of an equivalent dose of phenytoin sodium. Mean peak plasma phenytoin concentrations (Cmax) was 158% higher (P = 0.0277) following i.m. administration of fosphenytoin sodium compared to i.m. administration of phenytoin sodium. The mean area under the plasma total and free phenytoin concentration-time curve from time zero to 120 min (AUC(0-120)) following i.m. administration was also significantly higher (P = 0.0277) in fosphenytoin treated rabbits compared to the phenytoin group. However, there was no significant difference in AUC(0-180) between fosphenytoin and phenytoin-treated rabbits following i.v. administration. There was also no significant difference in the mean times to achieve peak plasma phenytoin concentrations (Tmax) between fosphenytoin and phenytoin-treated rabbits following i.m. administration. Mean plasma albumin concentrations were comparable in both groups of animals. Fosphenytoin was rapidly converted to phenytoin both after i.v. and i.m. administration, with plasma fosphenytoin concentrations declining rapidly to undetectable levels within 10 min following administration via either route. These results confirm the rapid and complete hydrolysis of fosphenytoin to phenytoin in vivo, and the potential of the i.m. route for administration of fosphenytoin delivering phenytoin in clinical settings where i.v. administration may not be feasible.

Animals↗
PubMedDate not supplied

The safety and kinetics of intramuscular quinine in Malawian children with moderately severe falciparum malaria.

The safety and kinetics of intramuscular quinine (10 mg salt/kg every 8 h for 3 doses) were assessed in Malawian children suffering from uncomplicated falciparum malaria, who were unable to take oral antimalarial drugs. Treatment was completed with oral pyrimethamine-sulfadoxine. The mean (+/- SD) peak plasma quinine concentration after the first injection was 9.0 (+/- 2.3) micrograms/ml, at 1.1 (+/- 0.7) h. Mean plasma concentrations increased further after the second and third doses to a maximum of 11.5 (+/- 2.6) micrograms/ml at 16.1 (+/- 3.2) h. No hypotension, hypoglycaemia or electrocardiographic abnormalities developed during quinine treatment. These results provide further evidence for the safety of intramuscular quinine in children with moderately severe malaria. Plasma concentrations of alpha 1-acid glycoprotein (AGP) were higher, and the degree of protein binding of quinine was greater, in acute malaria than in convalescence. There was a significant correlation between AGP concentration and the fraction of plasma quinine bound to plasma protein. These findings suggest a role for AGP in the binding of quinine in plasma in vivo and are of interest since unbound quinine is responsible for both the efficacy and toxicity of the drug.

Animals↗
PubMedDate not supplied

Mortality among drug addicts in Greater London.

During January 1970 to December 1974, 134 deaths in people aged 10-50 years investigated by coroners in Greater London were recorded as being due to drug addiction. Over three-quarters of the addicts were under 30, and 105 (78%) were male; 55 (41%) were unknown to the Home Office. Barbiturate overdose accounted for over half of the deaths, though two-thirds of these were in people registered as addicts to notifiable drugs. Since the Home Office index is concerned with addiction to one class of drugs only, it fails to reflect accurately the prevalence of all serious forms of addiction. Owing to the continuous change in drug-taking behaviour, however, probably no one method of assessment can provide a complete picture, and thus complementary research methods are essential.

Adolescent↗
PubMedDate not supplied

The disposition of primaquine in the isolated perfused rat liver. Effect of dose size.

The disposition of 14C-radiolabeled primaquine in the isolated perfused rat liver preparation was investigated after the administration of 0.5-, 1.5-, and 5.0-mg doses of the drug. The pharmacokinetics of primaquine in this experimental model were dependent on dose size. Increasing the dose from 0.5 to 5.0 mg produced a significant reduction in clearance from 11.6 +/- 2.5 to 2.9 +/- 1.0 ml X min-1. This decrease was accompanied by a disproportionate increase in the value of AUC from 25.4 +/- 5.9 to 1128.6 +/- 575.7 micrograms X min X ml-1, elimination half-life from 33.2 +/- 10.7 to 413.0 +/- 239.3 min, and volume of distribution from 547.7 +/- 153.1 to 1489.0 +/- 249.0 ml. Furthermore, primaquine exhibited dose dependency in its pattern of metabolism. While the carboxylic acid derivative of primaquine was not detected in perfusate after the 0.5-mg dose, it was the principal perfusate metabolite after the 5.0-mg dose. Primaquine was subject to extensive biliary excretion at all doses; the total amount of 14C radioactivity excreted in the bile decreased from 60 to 30% as the dose of primaquine was increased from 0.5 to 5.0 mg. The metabolite composition of radioactivity excreted in the bile was also examined. Total recovery of the administered radioactivity from bile, perfusate, and liver was essentially complete at all doses. The perfusate concentrations at the conclusion of each experiment (i.e. 5 hr) did not differ among dosage groups. By contrast, increased dose size produced a reduction in the amount of 14C radioactivity recovered in bile which was associated with increased levels of 14C in the liver.

Animals↗
PubMedDate not supplied

The role of iron in neurotoxicity: a study of novel antimalarial drugs.

The antimalarial drug artemisinin and its derivatives display neurotoxicity in animal studies in vivo and in neuronal cells in vitro. Their toxicity may be due to an interaction of iron with the endoperoxide bridge of the derivative to produce toxic free radicals and/or other toxic metabolites. In this study, 0.3 microM artemether (AEM) in the presence of 2 microM haemin significantly inhibited the outgrowth of neurites from differentiating NB2a neuroblastoma cells by up to 76%. The antioxidants ascorbic acid and glutathione completely protected against this toxicity at a concentration of 100 microM. AEM was found to be partially converted to two isomeric products, which were identified as the tetrahydrofuran acetate isomer of AEM and 3alpha-hydroxydesoxyartemether.

Animals↗