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Biomedical subjects

C F George

Publications and source records attributed to C F George.

At least 19 recordsLinked to original sources
PubMed1992

The influence of levodopa on gastric emptying in healthy elderly volunteers.

Paracetamol absorption and 99Tc-DTPA measurements have been used to determine the influence of levodopa on gastric emptying in 8 healthy elderly volunteers. In the absence of levodopa 7 subjects showed a rapid gastric emptying pattern by gamma-camera and a single major peak in the plasma concentration-time curve of paracetamol. One subject showed two rapid phases of gastric emptying separated by a period of negligible emptying and had 2 separate peaks in the paracetamol plasma concentration-time curve. In the presence of levodopa, the gamma-camera data for 6 subjects showed a pattern of gastric emptying consisting of 2 rapid phases separated by a plateau. In each case secondary peaks in the plasma concentration-time curve of paracetamol occurred about 30 min after the end of the plateau. The time to 90% emptying on the gamma scan was increased significantly from 40 min to 65 min in the presence of levodopa. Comparison of the present data with those reported previously indicates that levodopa affects gastric emptying in the both elderly and young volunteers to a similar extent.

Acetaminophen↗
PubMed1992

The metabolism of cyclamate to cyclohexylamine and its cardiovascular consequences in human volunteers.

A group of 194 diabetic patients were given calcium cyclamate (1 g/day as cyclamic acid equivalents) for a period of 7 days. Blood and urine samples were collected to determine the formation of cyclohexylamine, which is an indirectly acting sympathomimetic amine. Blood pressure and heart rate were recorded before and after treatment. Urine samples were collected each day and analyzed for cyclamate (to check compliance) and cyclohexylamine (to monitor the development of metabolizing activity). After 7 days intake most individuals (78%) did not excrete significant amounts of cyclohexylamine (less than 0.1% of the daily dose of cyclamate) but a small number (8; 4% of the group) excreted more than 20% of the daily dose as cyclohexylamine in the urine. Similar interindividual variations were found in the plasma concentrations of cyclohexylamine after 7 days intake of cyclamate, with 8 individuals having concentrations of 300-1942 ng/ml. The changes in cardiovascular parameters in these 8 subjects between pre- and postdosing were similar to those found in 150 subjects with plasma cyclohexylamine concentrations less than 10 ng/ml. Twenty of the subjects were restudied after receiving calcium cyclamate for 2 weeks at a daily dose equivalent to 2 g of cyclamic acid (0.66 g tds). Plasma concentrations of cyclohexylamine, heart rate, and blood pressure were measured every 30 min for a period of 8 hr (one dose interval) after the final dose. Twelve patients had plasma concentrations of cyclohexylamine greater than 10 ng/ml (89-2043 ng/ml) at the start of the dose-interval investigations. There were no transient increases or decreases in plasma concentrations of cyclohexylamine which might have resulted in a transient change in blood pressure or heart rate. These data indicate that the metabolism of cyclamate (2 g/day) to cyclohexylamine would not affect blood pressure or heart rate even in individuals with high metabolizing ability.

Adult↗
PubMed1992

The influence of posture on the pharmacokinetics of orally administered nifedipine.

1. Nifedipine (20 mg as capsules) and soluble paracetamol (1 g) were co-administered to eight healthy young volunteers on three separate occasions, following which in random order they stood, lay on their left side or lay on their right side for 4 h. 2. The time to maximum plasma concentration of paracetamol was significantly lower when standing or lying on the right side compared with recumbent left, indicating more rapid gastric emptying. 3. The times to maximum plasma concentrations of nifedipine and its metabolite produced at first pass were reduced when standing or lying on the right side. These postures were associated with significantly higher peak plasma concentrations and AUC values of nifedipine but not of its nitropyridine metabolite. 4. The increase in heart rate following nifedipine administration was significantly greater when lying on the right side compared with the left. 5. The data are consistent with transient saturation of first pass metabolism of nifedipine with postures which favour rapid gastric emptying. The results demonstrate the importance of defining the precise posture in studies in which pharmacokinetic and pharmacodynamic measurements are made on drugs which are absorbed rapidly and are subject to presystemic elimination.

Acetaminophen↗
PubMed1992

HLA-D-region genomic DNA restriction fragments in DRw15 (DR2) familial narcolepsy.

Restriction fragment length polymorphism (RFLP) associated with the three human lenkocyte antigen (HLA)-D-region gene-specific cDNA probes (gene-specific DQ alpha, DQ beta and DP beta) was evaluated in two Caucasian families from southwestern Ontario, each with two confirmed narcoleptic siblings. The special feature of the two families is that the affected members are not necessarily DRw15 (previously DR2) positive. In family 1, of the two affected sibs one is DRw15 positive, whereas in family 2 all members including the two affected sibs are DRw15 negative. There is no association between narcolepsy and HLA haplotype in the two families. Further, the polymorphic DNA band patterns generated by a number of restriction enzymes do not show a relationship with the presence or absence of narcolepsy. The probe-specific DNA and patterns however do follow the HLA haplotypes associated with the DQ and DR loci. These results suggest that in DRw15-negative narcolepsy, the DNA patterns are not informative with respect to diagnosing or predicting the presence of narcolepsy. Further, such results argue for genetic heterogeneity in narcolepsy, and the role of DRw15 in the development of the disease could at best be viewed as contributory and not essential.

DNA↗
PubMed1991

Ethnic differences in the pharmacokinetics of oral nifedipine.

1. The pharmacokinetics of a single oral dose of 20 mg nifedipine, given as capsules, has been compared in five South Asian volunteers with data for 27 Caucasian volunteers. 2. The area under the plasma concentration-time curve (AUC) of nifedipine was three fold higher in South Asians (989 +/- 166 ng ml-1 h) than in Caucasians (323 +/- 116 ng ml-1 h). 3. The ratio of the AUC of nifedipine to that of the nitropyridine analogue, which is formed largely as a first pass metabolite, was significantly higher in South Asians (4.6 +/- 1.9) than in Caucasians (2.3 +/- 1.1) indicating a lower first pass metabolism in South Asians. 4. The terminal half-lives of nifedipine and the nitropyridine metabolite were significantly greater in South Asians than in Caucasians. 5. Consumption of a spicy curry diet for 3 days by Caucasians did not significantly affect the pharmacokinetics of a single oral dose of nifedipine. 6. The treatment of patients of South Asian origin with nifedipine should be initiated with lower doses than would be given to Caucasians.

Administration, Oral↗
PubMed1991

The influence of protein containing meals on the pharmacokinetics of levodopa in healthy volunteers.

1. The pharmacokinetics of levodopa and paracetamol after single oral doses have been investigated in eight healthy young volunteers in the fasted state and following isocaloric meals containing either 10.5 g or 30.5 g of protein. 2. The initial peak and maximum plasma drug concentrations and the times at which these occurred were not affected by food. 3. The mean area under the plasma concentration-time curve (AUC) for paracetamol following an overnight fast did not differ significantly from that observed following the low and high protein meals. 4. By contrast, the AUC for levodopa following the low protein meal (193.9 +/- 15.7 micrograms ml-1 min) was significantly lower compared with administration in the fasted state (216.5 +/- 26.1 micrograms ml-1 min). However, there were no significant differences in the kinetics of levodopa between the fasting state and following the high protein meal. 5. There was no evidence that consumption of a meal containing 30.5 g of protein impaired either the rate or extent of absorption of levodopa. Therefore the reported beneficial effects of a low protein diet in the treatment of patients with Parkinson's disease probably result from reduced competition for levodopa transport across the blood-brain barrier.

Acetaminophen↗
PubMed1991

Gastric emptying in healthy volunteers after multiple doses of levodopa.

1. Oral levodopa frequently produces an episodic delay in gastric emptying which leads to multiple peak concentrations of the drug in plasma. We have studied the effects of multiple dosing of levodopa on gastric emptying and levodopa absorption in eight healthy young volunteers in a randomised two-way cross-over study. 2. The plasma concentration-time curves for levodopa were measured after three oral doses of 125 mg given at 2 h intervals and compared with the concentration-time curve for levodopa following administration of two doses of placebo and a single oral dose of 125 mg. 3. A low incidence of multiple peak plasma concentrations of levodopa was detected after all doses of levodopa. The area under the plasma concentration-time curves (AUC) for the final dose of levodopa (150.8 +/- 22.0 micrograms ml-1 min) was lower than for the two preceding doses (205.7 +/- 41.8 and 199.5 +/- 51.8 micrograms ml-1 min) but not different from that of the single dose given at the same time of day (141.7 +/- 29.1 micrograms ml-1 min). This indicates that the lower AUC of the final dose of levodopa was related to the time of administration and not a result of the two preceding doses. 4. The absence of any significant effects of preceding doses of levodopa on gastric emptying was confirmed a) by co-administration of soluble paracetamol, as a marker of gastric emptying, with the second dose of levodopa or placebo and b) by co-administration of radiolabelled DTPA and gamma-camera imaging with the final dose of levodopa on the multiple dosing day and the single dose of levodopa on the placebo day.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaminophen↗
PubMed1991

Oral amino acids and gastric emptying: an investigation of the mechanism of levodopa-induced gastric stasis.

To investigate possible mechanisms of levodopa-induced gastric stasis, we have studied the effect of other amino acids on gastric emptying. The large neutral amino acid tryptophan delays gastric emptying in the dog at molar concentrations below those required to stimulate duodenal osmoreceptors. In healthy volunteers, we have shown that neither tryptophan nor the small neutral amino acid glycine delayed gastric emptying when given in concentrations similar to those of levodopa which produce gastric stasis. The study suggests that levodopa does not inhibit gastric emptying by an effect on duodenal amino acid receptors or via osmoreceptors.

Acetaminophen↗
PubMed1991

Juvenile onset narcolepsy in an individual with Turner syndrome. A case report.

We describe an 8 year old girl who presented with excessive daytime sleepiness and frequent falling. Following extensive investigations, the diagnosis of both narcolepsy and Turner Syndrome were confirmed. To our knowledge, this is the first report of these two conditions in the same individual. Both conditions are common, but the early expression of narcolepsy is unusual. Although there is a genetic basis for each, the two conditions are not necessarily related since Turner is an X-linked abnormality, while narcolepsy has an autosomal basis. Nonetheless we wonder if the hormonal balance of Turner Syndrome might have some role to play in the early expression of narcolepsy.

Arousal↗
PubMed1990

Drug therapy for Parkinson's disease in the elderly.

The diagnosis and management of Parkinson's disease in the elderly is complicated by the common presence of multiple pathology and age related changes in drug handling. Accurate diagnosis requires a high index of suspicion combined with careful assessment before and after a trial of therapy. A multidisciplinary approach is required to help the patient, and their carer, cope with the fundamental disabilities resulting from Parkinson's disease. The elderly are more susceptible to side effects from antiparkinsonian medication and close supervision is therefore essential.

Aged↗
PubMed1979

The rationale of treating high blood pressure in the elderly.

The elderly are at risk from stroke and cardiac complications of hypertension. There is strong circumstantial evidence to indicate that these risks may be reduced by hypotensive therapy. However, the decision to treat must be taken after careful appraisal of the patient and, because the risks of therapy are higher in this age group, the choice of drugs should be restricted.

Adrenergic beta-Antagonists↗
PubMed1979

The effect of ageing on the hepatic clearance of propranolol.

1. Plasma propranolol concentrations were measured in healthy old and young subjects following single oral doses of 40 mg, single i.v. infusions of 0.15 mg kg-1 and after nine 40 mg oral doses given four times daily. 2. In each of the three studies, the elderly had higher plasma propranolol concentrations than the young despite having similar apparent volumes of distribution. 3. The terminal half-life of propranolol was similar in the two groups after oral propranolol but significantly shorter in the young after intravenous dosing (P less than 0.05). 4. The bioavailability assessed from the concentration-time curves after i.v. and oral dosing was greater in the elderly (P less than 0.05). 5. The differences between peak concentrations observed in old and young subjects after single oral doses were maintained during chronic therapy and there was a correlation between the individual values obtained on multiple therapy with that after a single dose (P less than 0.05). 6. Ageing appears to affect the pharmacokinetics of propranolol in two ways. Firstly, distribution to the tissues appears to be slowed. Secondly, the increased bioavailability following oral administration suggests diminished intrinsic clearance by metabolism.

Administration, Oral↗
PubMed1979

Chlormethiazole--no hangover effect but not an ideal hypnotic for the young.

The hangover effects of 768 mg chlormethiazole, an hypnotic with a half-life of approximately 4 hr, were compared with those of placebo in a double-blind cross-over study in 8 young subjects. Ten hours after dosing there were no differences between the preparations in the subjects' psychomotor performance, EEG sleep scores, or visual analogue ratings. Thus, an hypnotic which is rapidly removed from the body may confer considerable advantages. However, all 8 subjects had unpleasant nasal symptoms following chlormethiazole, and it is therefore not an ideal hypnotic for this age group.

Adult↗