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Biomedical subjects

N W Spurling

Publications and source records attributed to N W Spurling.

6 recordsLinked to original sources
PubMed1992

Dose selection for toxicity studies: a protocol for determining the maximum repeatable dose.

1. A three-stage protocol is described for a dose-ranging study which defines the maximum repeatable dose (MRD) and provides a preview of the toxicology of new, pharmacologically active, substances before commencing the first formal regulatory toxicity studies, usually of 2 or 4 weeks duration. 2. Additionally, a range of toxicokinetic (TK) data relevant to protocol design for formal studies is generated. 3. Stage A is a dose incrementation process in which the MRD is provisionally determined and basic TK values generated. 4. In stage B the animals are dosed daily for at least 7 d, the MRD is substantiated and a wider range of TK data obtained. 5. In stage C, each of the dose levels identified for a formal study is administered once to investigate the relationship of doses to TK data. 6. This protocol can be completed using as few as 24 rats or six dogs (or primates). 7. Selection of dose levels for the first formal studies can be greatly aided by the results of a well-designed dose-ranging study including TK data. 8. For particularly toxic substances, the findings of studies based on this protocol have frequently been sufficiently clear to warrant early termination of their development.

Animals↗
PubMed1991

Phospholipase C-sensitive factor VII complexes in dog plasma.

We report the presence of a phospholipase c-sensitive activated factor VII complex in canine plasma after feeding a special diet. Low levels of complex was observed in the fasting state. The response to feeding in terms of activated factor VII varied markedly among the dogs investigated.

Animals↗
PubMed1989

Ondansetron: pre-clinical safety evaluation.

A programme of pre-clinical safety evaluation of ondansetron has been undertaken which involved a series of studies - single dose studies, repeat dose studies, reproduction studies, genotoxicity studies, oncogenicity studies, local irritancy studies, and a hypersensitivity study. Ondansetron was found to have a very good safety profile, and the only toxicity identified was associated with central nervous system activity when near lethal doses were administered. It was not genotoxic and had no reproductive or oncogenic potential.

Administration, Oral↗
PubMed1987

[The protein C inhibitory system].

The chemical and physical characteristics of the individual components of the protein-C inhibiting system, protein C, thrombomodulin, protein S and the inhibitor of the activated protein C are summarized in a survey, with their mutual relations and their physiological impact on the course of the coagulating and fibrinolytic systems being represented. Finally, the clinical implications of a hereditary and acquired protein C deficiency, of a diminished protein S level and a lowered inhibitor of the activated protein C are discussed. The complications caused by a rapid decline of protein C values after administration of coumarin derivates are referred too.

Blood Proteins↗
PubMed1978

The influence of residual factor VII on the sensitivity of brain thromboplastin.

One-stage prothrombin times of normal and of factor VII-deficient beagle plasma were determined with two types of beagle brain thromboplastin, one prepared from normal beagles and the other from factor VII-deficient beagles. There was little difference between the reagents in the prothrombin times obtained for normal plasma. However, when factor VII-deficient plasma was tested, reagent prepared from factor VII-deficient beagles gave considerably longer prothrombin times than were obtained with the normal reagent and the difference increased with increasing reagent concentration to a maximum at 140 mg/ml. Prothrombin times of a series of mixtures of normal and factor VII-deficient plasma indicated that the presence of only 1/90 part of normal plasma was necessary to compensate for the difference between the two reagents. Determination of the iron content of the reagent suggested that the microcirculation of an average brain contained some 1.8 g of whole blood. The finding that brain thromboplastin prepared from factor VII-deficient beagles is more sensitive to a deficiency of factor VII in plasma, presumably a result of the smaller quantity of factor VII present in the reagent, is compatible with the known kinetics of extrinsic coagulation.

Animals↗