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Biomedical subjects

J Moncrieff

Publications and source records attributed to J Moncrieff.

At least 55 records · Page 3Linked to original sources
PubMed1991

Absence of polymorphism of sparteine oxidation in the South African Venda.

1 This study has found no occurrence of poor metabolism of sparteine within a South African Venda population of 97 subjects. 2 On the basis of MR (metabolic ratio) the mean and distribution of the results are very similar to those found in Ghanaians. 3 The distribution is also similar to that for fast metabolizers in Caucasians. 4 It is concluded that different P450 cytochromes are responsible for immediate oxidation of debrisoquine and sparteine, but that both may be activated by the same P450 reductase.

Adult↗
PubMed1990

Fraction of theophylline in sustained-release formulation which is absorbed from the large bowel.

In a cross-over study of six healthy male volunteers, 500 mg theophylline was administered either as plain tablets or in a sustained release preparation. On each occasion 2 g of non-enteric coated sulphasalazine was administered simultaneously as the time of appearance of sulphapyridine, the product of hydrolysis, in the blood provides an approximation of the oral--caecal transit time. The mean fraction absorbed--time profile was calculated from serial serum concentration measurements of theophylline by a modification of the Wagner-Nelson equation. The mean cumulative fraction of the dose absorbed following administration of the plain tablets was maximal at 3 h i.e. approximately 3 h ahead of the mean oral-caecal transit time, which was 5.9 h. Thus complete absorption occurred in the small intestine. With the sustained--release formulation, approximately only half of the dose was absorbed at the time the medication reached the large bowel i.e. at about 5.4 h. Absorption continued and at least 38% of the administered dose was additionally absorbed over the next 25 h. A reliable lengthened dosage interval is therefore possible with this particular sustained--release formulation.

Adult↗
PubMed1990

The mean cumulative fraction absorbed-time profiles of paracetamol as an index of gastric emptying.

The purpose of this study was to measure gastric emptying by using the cumulative fraction absorbed-time profiles of paracetamol. To evaluate the validity of the method as an index of gastric emptying, six healthy male volunteers were entered into an ethically approved trial using different regimens of cholinergic enhancing (i.e. metoclopramide and neostigmine) and blocking agents (i.e. atropine and pirenzepine) and the results were compared with the bioavailability (i.e. Cmax, Tmax, AUC) parameters of paracetamol as an index of gastric emptying. The cumulative fractional absorption of paracetamol appears to be a valuable index for the measurement of gastric emptying.

Acetaminophen↗
PubMed1989

Determination of pharmacological levels of harmane, harmine and harmaline in mammalian brain tissue, cerebrospinal fluid and plasma by high-performance liquid chromatography with fluorimetric detection.

Increased blood aldehyde levels, as occur in alcohol intoxication, could lead to the formation of beta-carbolines such as harmane by condensation with indoleamines. Endogenous beta-carbolines, therefore, should occur in specific brain areas where indoleamine concentrations are high, whilst exogenous beta-carbolines should exhibit an even distribution. The author presents direct and sensitive methods for assaying the beta-carbolines harmane, harmine and harmaline in brain tissue, cerebrospinal fluid and plasma at picogram sample concentrations using reversed-phase high-performance liquid chromatography with fluorimetric detection and minimal sample preparation. Using these assay methods, it was found that the distribution of beta-carbolines from a source exogenous to the brain results in a relatively even distribution within the brain tissue.

Alkaloids↗
PubMed1989

Metoprolol alpha-hydroxylation polymorphism in the San Bushmen of southern Africa.

1. The metabolic oxidation of metoprolol has been studied in a group of 98 San Bushmen. 2. The amounts of metoprolol and alpha-hydroxy metoprolol excreted in 0-8 h urine collection, after dosing with 100 mg metoprolol, were measured and the metabolic ratio (% dose excreted as metoprolol/% dose excreted as alpha-hydroxy metoprolol) calculated. 3. Frequency distribution and probit plots of the metabolic rate data showed a bimodal distribution with 4.1% of the population exhibiting slow metabolism with an MR greater than 10. 4. These results are much less than found in Caucasians (8.4%) but very different from the unimodal distribution found for Nigerians. 5. A previous study in the same group of Bushmen had revealed that 18 of 96 subjects were poor or non-metabolizers of debrisoquine to 4-hydroxy debrisoquine, but only one of the poor metoprolol metabolizers was a poor metabolizer of debrisoquine. 6. On the basis of these results, the claim of debrisoquine type of polymorphism for beta-adrenoceptor antagonists found in Caucasians cannot be extrapolated to the San Bushmen, and one must query the use of debrisoquine as measure of oxidative status in any group other than Caucasians.

Black People↗
PubMed1989

Non-correlation between debrisoquine and metoprolol polymorphisms in the Venda.

1. The metabolic 4-hydroxylation of debrisoquine has been studied in a group of 98 black African villagers in Vendaland. 2. The metabolic alpha-hydroxylation of metoprolol has been studied in 94 of the same black African villagers. 3. A 4% prevalence of poor oxidative metabolism of debrisoquine and a 7.4% incidence of poor oxidation of metoprolol were found. The 4% result for debrisoquine differs considerably from the 19% found in San Bushmen, 30% in Hong Kong Chinese, 9% in Britains and 0% in Nigerians and Japanese, whilst the 7.4% result for metoprolol compares with 8.4% in Britains but differs from 0% in Nigerians and 4.1% in San Bushmen. 4. None of the poor oxidative metabolizers of debrisoquine were also poor oxidative metabolizers of metoprolol. This is contrary to results in British and Nigerian subjects where defective oxidation of metoprolol co-segrates with that of debrisoquine. 5. No similarities were found between the Venda metabolic ratio (MR) distributions and either extensive or poor MR distributions in Britains or Nigerians.

Black People↗
PubMed1988

Polymorphism of the 4-hydroxylation of debrisoquine in the San Bushmen of southern Africa.

1. The metabolic oxidation of debrisoquine has been studied in a group of 96 San Bushmen. 2. The amounts of debrisoquine and 4-hydroxy-debrisoquine excreted in 0-8 h urine were measured and the metabolic ratio (% dose as debrisoquine/% dose as 4-hydroxy-debrisoquine) calculated. 3. On the basis of Caucasian criteria, that metabolic ratios greater than 12.6 represent poor metabolizers, 19% of the Bushmen were poor metabolizers in contrast to the 8-10% found in Caucasian studies. 4. Probit plots showed four modes may be present in the data, which may represent at least three isozymes of the relevant enzyme which may also differ from the Caucasian isozymes.

Black People↗
PubMed1987

Antipyrine metabolism in the Venda.

The excretion of antipyrine metabolites over 48 h as percentage dose and the antipyrine kel and metabolite formation rate constants have been measured for 20 healthy Venda Africans. To allow comparison with published data from inter-ethnic studies with antipyrine, subjects were selected who had assumed a western life and diet. The values (mean +/- SE) for excretion of the metabolites, 4-hydroxyantipyrine (4OHA), norantipyrine (NORA) and 3-hydroxymethylantipyrine (3HMA) as percentage dose were 26.17 +/- 0.34, 7.44 +/- 0.34 and 13.28 +/- 0.31 respectively. The total of the three metabolites was 49.56 +/- 0.33. These results differ significantly from the values found for groups of Canadian students of Oriental and Caucasian backgrounds. The values (mean +/- SE) found for the antipyrine elimination rate constant and the metabolite formation rate constants of 4OHA, NORA and 3OHA were 6.56 (+/- 0.56) X 10(-2), 2.05 (+/- 0.24) X 10(-2), 0.60 (+/- 0.09) X 10(-2) and 1.06 (+/- 0.16) X 10(-2) respectively. Only the NORA formation rate constant showed any significant difference with the results obtained for Americans, although the Venda exhibited a wider distribution of the 3HMA data. The linearity of the probit plots obtained suggest that the subjects selected are homozygous for the oxidations investigated. The marked difference found in comparison with Caucasian and Oriental data on the one hand and American data on the other, also implies a marked difference between the Caucasian and Oriental data and the American data.(ABSTRACT TRUNCATED AT 250 WORDS)

Antipyrine↗
PubMed1987

Paracetamol conjugation: an interethnic and dietary study.

To test whether dietary or hereditary factors affect paracetamol metabolism, two groups of Venda and a group of Caucasian medical students were investigated. The Venda groups were selected as traditionally living villagers and those who followed a Western life-style. Salivary concentrations of paracetamol and urinary amounts of the glucuronide and sulphate metabolites eliminated over 22 h were determined by HPLC. The metabolite formation rate constants and the percentage of the dose eliminated as each metabolite were calculated. No significant differences were found between the data for total Venda, rural Venda, westernized Venda and Caucasian students for the calculated metabolite parameters. Thus environmental effects showed no apparent influence on the sulphide and glucuronide conjugation of paracetamol, and no hereditary effect was evident between the Venda and Caucasians.

Acetaminophen↗
PubMed1985

Chronopharmacokinetics of paracetamol in normal subjects.

The chronopharmacokinetics of paracetamol was studied in six male volunteers. Serum concentrations of paracetamol were determined after a single oral dose of 1 g, on three occasions, spaced at least 1 week apart. Plasma drug concentration vs time curves were obtained after dosage at 08.00 h (Day 1), 14.00 h (Day 2) and 20.00 h (Day 3), under standardized conditions. Pharmacokinetic parameters compared were t1/2,alpha, t1/2,Z, tmax, Cmax and AUCpo. No statistically significant differences were found.

Acetaminophen↗
PubMed1985

Antipyrine metabolism in African villagers.

Antipyrine clearance has been measured from serial serum samples in 49 healthy black Africans from a village in Southern Africa. The subjects follow a lifestyle which minimally exposes them to environmental inducing or inhibiting agents. Food is mainly maize cereal with a protein content of only about 8.8%, together with greens. Antipyrine clearance, half-life and apparent volume of distribution (mean +/- SD) were, respectively, 0.538 +/- 0.163 ml min-1, kg-1, 14.81 +/- 6.5 h and 0.626 +/- 0.075 litre/kg. These results do not differ significantly from the mean values found in a group of lactovegetarian Indo-Pakistani immigrants to Britain. This would suggest that the major environmental determinant influencing hepatic mixed-function oxidase activity is the presence or absence of meat in the diet. However, the relative contributions of environment and heredity will be difficult to determine.

Adult↗
PubMed1985

Paracetamol metabolism in African villagers.

Paracetamol clearance has been measured from serial serum samples in 49 healthy black Africans from a village in Southern Africa. The subjects are minimally exposed to known environmental inducing or inhibiting agents and the staple diet consists of maize cereal and greens. The mean clearance (+/- SD) was 4.98 +/- 1.61 ml min-1 kg-1, which is significantly faster than the values found in previous investigations with paracetamol in whites and Asian immigrants in London. The mean half-lives were fairly similar but the apparent volumes of distribution were also found to be larger in the present study. The ethnic difference in paracetamol kinetics identified in this study is possibly genetically controlled.

Acetaminophen↗