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Biomedical subjects

D E Case

Publications and source records attributed to D E Case.

8 recordsLinked to original sources
PubMed1977

Safety of Hibitane. I. Laboratory experiments.

The safety evaluation of chlorhexidine (Hibitane) in animal species will be briefly reviewed. The relevance of these studies to human use will be discussed, and species comparisons made where possible. Animal studies with chlorhexidine were begun more than two decades ago and the evaluation of its safety has been under continual review ever since. Chlorhexidine is poorly absorbed after oral administration, well tolerated after parenteral administration and its percutaneous absorption is abolutely minimal. No clinical or histological effects have been obtained in any animal study to cause hesitation in the light of proliferating applications of chlorhexidine in human use. The various toxicological studies in animals will be described and in particular the results of a 2-year study in rats will be outlined. In this, as an in earlier long-term study, there were no effects whatsoever to suggest that chlorhexidine treatment could give rise to any kind of tumourigenic effect or any other toxic sign.

Administration, Oral↗
PubMed1975

Blood level studies with viloxazine hydrochloride in man.

1 The pharmacokinetic characteristics of a new antidepressant, viloxazine hydrochloride, (ICI 58,834, Vivalan), have been investigated in four separate studies. 2 In Study 1, blood levels were measured over a period of 24 h after single doses of viloxazine hydrochloride from 10-100 mg (expressed as base). In Study 2, blood levels were measured over 24 h, during which three single doses of viloxazine hydrochloride (80 mg, expressed as base) were given 4 h apart. In Study 3, blood samples and urine and faeces were collected for 96 h after doses of 40 and 100 mg of [14C] viloxazine hydrochloride (40 muCi). In Study 4, 1 h blood levels were measured at weekly intervals during a comparative clinical trial in which viloxazine was given at a dose of 100 mg four times a day. 3 The half-life of the drug is in the range 2-5 h with maximum blood levels occurring in 1-4 h of the oral dose. Maximum blood levels are proportional to the oral dose given over the range studied (0.76(mug/ml)/(mg/kg)). The drug is very well absorbed orally, only 2% being found in faeces. Repeated dosing at 4 hourly intervals leads to slightly higher blood levels after the second, but not subsequent, doses. No accumulation was seen from week to week in depressed patients. No regular sex difference was seen in the pharmacokinetic characteristics of viloxazine hydrochloride but two females in one study did show a markedly higher maximum blood level and apparently longer half-life than the males. 4 It is concluded that viloxazine is rapidly and almost totally absorbed after an oral dose, and has a shorter half-life than the tricyclic antidepressants; therapy with it should be easily controllable.

Adult↗
PubMed1975

The disposition and metabolism of I.C.I. 58,834 (viloxazine) in animals.

1. 2-(2-Ethoxyphenoxymethyl-2,3,5,6-tetrahydro-1,4-oxazine (I.C.I. 58,834) has been prepared in three different 14C-labelled forms and its absorption, distribution, metabolism and elimination studied in six animals species. 2. In all species I.C.I. 58,834 was well absorbed after oral administration and extensively metabolized. Excretion via the kidney was the main route of elimination. 3. In the rat the major metabolic pathway is o-dealkylation and sulphate conjugation; the dealkylated metabolite was detected in brain extracts. A novel type of polar metabolite was isolated from rat urine, apparently a conjugate with sulphate and hippurate. 4. The metabolic pathways in beagle dogs include hydroxylation of the phenyl ring (and subsequent conjugation), N-methylation, formation of the N-methyl-N-oxide, and oxidation of the oxazine ring. 5. Maximum blood levels of I.C.I. 58,834 in dogs were unchanged during eight weeks daily administration and the half-life was 2.5-3 h. I.C.I. 58,834 is the main component in dog blood. Rat serum contains mainly conjugates of dealkylated I.C.I. 58,834 and the parent compound is a minor component. 6. None of the metabolites has significant CNS activity and activity observed following administration of I.C.I. 58,834 is due primarily to the parent compound.

Animals↗
PubMed1975

The disposition and metabolism of I.C.I. 58,834 (viloxazine) in humans.

1. 2-(2-Ethoxyphenoxymethyl)-2,3,5,6-tetrahydro-1,4-oxazine (I.C.I. 58,834) in three 14C-labelled forms, given orally to two male volunteers, was completely absorbed, extensively metabolized and rapidly eliminated via the kidney. 2. O-Dealkylation, the major metabolic pathway in the rat, was not significant in man. 3. The major component in blood at all times was I.C.I. 58,834, which had a blood half-life of 4 h. The level of 14C in blood at 31 h was near the limit of detection. 4. The observed activity of the drug appears to be due to the parent compound alone.

Administration, Oral↗
PubMed1975

Incorporation into endogenous metabolic pathways of small fragments derived from I.C.I, 58,834(vioxazine).

1. Metabolic degradation of the tetrahydro-oxazine ring of 2-(2-ethoxyphenoxymethyl)-2,3,5,6-tetrahydro-1,4-oxazine (I.C.I. 58,834) gives rise to one- or two-carbon fragments which are utilized by endogenous metabolic pathways. 2. Evidence of this in dogs is shown by the 14C-labelled residues in tissues, 14C-labelled material in blood which has a half-life of three weeks, and elimination of [14C]urea in urine. 3. The same phenomenon occurs in rat, mouse and man, but to a smaller extent than in the dog. 4. Intravenous administration of [14C]ethanolamine to a dog gave rise to residual 14C blood levels with a half-life comparable to that produced by metabolic incorporation of 14C from 14C-I.C.I. 58,834.

Administration, Oral↗