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Biomedical subjects

R Lancaster

Publications and source records attributed to R Lancaster.

At least 19 recordsLinked to original sources
PubMed1983

Genetically determined oxidation capacity and the disposition of debrisoquine.

1 The disposition in urine of debrisoquine and its hydroxylated metabolites has been studied in subjects of the 'extensive metabolizer' (EM; n = 5) and 'poor metabolizer' (PM; n = 5) phenotypes. The 4-hydroxylation of debrisoquine by PM subjects following a 10 mg oral dose was capacity-limited and displayed significant dose-dependency over a range of 1-20 mg. In contrast, the EM subjects' ability to perform this metabolic oxidation did not deviate from first-order kinetics over a dose range of 10-40 mg. 2 The disposition of debrisoquine in plasma following a 10 mg oral dose has been studied in EM (n = 4) and PM (n = 3) subjects. Whilst PM subjects displayed significantly higher plasma levels of debrisoquine at all time points following 1 h post-dosing, and higher values for areas under the plasma concentration-time curve (EM: 105.6 +/- 7.0 ng ml-1 h; PM: 371.4 +/- 22.4 ng ml-1 h, 2P less than 0.0001), neither debrisoquine plasma half-life (EM: 3.0 +/- 0.5 h; PM: 3.3 +/- 0.4 h) nor renal clearance of the drug (EM: 152.8 +/- 30.3 ml min-1; PM: 137 +/- 4.5 ml min-1) displayed significant inter-phenotype differences. 3 The results of these investigations show that the phenotyping of individuals for debrisoquine oxidation status by means of a 'metabolic ratio' derived from a single 0-8 h urine sample has a sound kinetic basis. The kinetic differences between the two phenotypes would strongly suggest that the metabolic defect manifested in PM subjects is one of pre-systemic elimination capacity.

Administration, Oral↗
PubMed1981

The St. Mary's Hospital sleep questionnaire: a study of reliability.

A systematic sleep questionnaire has been devised for assessing the previous night's sleep of a subject. It has been designed for repeated use. It is completed by the subject and is framed with the needs of the hospital patient in mind. In the present study it was given to 93 subjects in four different groups: 16 surgical inpatients, 21 medical inpatients, 32 psychiatric inpatients (in a general hospital unit), and 24 normal volunteers. Test retest reliability correlations have been derived using a nonparametric correlation coefficient (Kendall's tau). Each of the items achieved statistically significant reliability (p less than 0.0001) in all four groups, with the value for tau on the total sample varying from 0.70 to 0.96. The St. Mary's (or SMH) Sleep Questionnaire is put forward as an instrument that is a systematic inquiry into the subject's experience of sleep and that is composed of items of demonstrable reliability.

Adolescent↗
PubMed1979

The metabolism of [14C]-debrisoquine in man.

1 The synthesis of [14C]-debrisoquine hydrochloride and 4-hydroxy-debrisoquine sulphate is described. 2 The metabolic fate and excretion profile in both urine and faeces of 14C-labelled debrisoquine was studied in five healthy human subjects. 3 Investigations showed that the drug is well-absorbed after a single oral dose of 32 mg and quantitatively eliminated from the body within three days. 4 4-Hydroxy-debrisoquine is the major metabolite of debrisoquine, although significant amounts of 5-,6-, 7- and 8-hydroxy-debrisoquine are also formed. 5 Electron-capture gas chromatography is a useful method for measuring debrisoquine and its five hydroxylated metabolites in urine at the pg level.

Adult↗
PubMed1978

Polymorphism of carbon oxidation of drugs and clinical implications.

Eight volunteers previously phenotyped for their ability to hydroxylate debrisoquine (four extensive metabolisers (EM), four poor metabolisers (PM) were investigated for their metabolic handling of guanoxan and phenacetin. All three drugs are oxidised at carbon centres. Oxidative dealkylation of phenacetin was determined by measuring the rate of formation of paracetamol. The EM subjects excreted mostly metabolites of guanoxan (mean 29% of dose), whereas the PM group excreted large amounts of unchanged drug (48% of dose). The rate of formation of paracetamol was noticeably slower in the PM group, and, when analysed by minimum estimates of apparent first-order rate constants, the difference between the two phenotypes was significant. Thus the hydroxylation defect shown for debrisoquine metabolism carries over to the oxidative metabolism of phenacetin and guanoxan. Some 5% of the population are genetically defective hydroxylators of drugs. Thus methods for evaluating the metabolism of new drugs in respect of usage and side effects need to be revised.

Acetaminophen↗
PubMed1977

Polymorphic hydroxylation of Debrisoquine in man.

Debrisoquine and its primary metabolite, 4-hydroxydebrisoquine, were measured in the urine of 94 volunteers after a single oral dose of 10 mg debrisoquine. The ratio between excreted debrisoquine and its metabolite was bimorphically distributed in the study population. Family studies supported the view that alicyclic 4-hydroxylation of debrisoquine is controlled by a single autosomal gene and that a defect in this metabolic step is caused by a recessive allele.

Administration, Oral↗
PubMed1976

The effect of pindolol on plasma renin activity and blood pressure in hypertensive patients.

1 The effect of pindolol administered to twenty-six patients with hypertension of unknown origin was compared with respect to blood pressure and plasma renin activity change after increase of the dose over a period of 6 weeks. 2 There was no clear correlation between the fall of plasma renin activity, which in some patients was very marked, and the fall in blood pressure. Some patients with a fall in plasma renin activity did not drop their pressure. Conversely, some with a fall of pressure did not drop their plasma renin activity. 3 The addition of hydrochlorothiazide to the pindolol finally caused further lowering of the blood pressure in all but one patient and the plasma renin activity rose in all but two patinets. There was no clear correlation between change in plasma renin activity and the effect on blood pressure.

Adult↗