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Biomedical subjects

C F George

Publications and source records attributed to C F George.

At least 91 records · Page 5Linked to original sources
PubMed1987

Factors affecting the pharmacokinetics of nifedipine.

The plasma pharmacokinetics of nifedipine and the formation of its metabolites have been studied in volunteers under conditions which would affect the activity of the cytochrome P-450 system. The pharmacokinetics of a 10-mg capsule of nifedipine were not significantly different between smokers and non-smokers of similar age. After pretreatment with cimetidine, which inhibits the activity of cytochrome P-450, the peak plasma concentration and area under the plasma-time concentration curve for nifedipine were increased by a mean 84%. In contrast, pre-treatment with ranitidine which has little effect on cytochrome P-450, did not significantly alter nifedipine pharmacokinetics. Smoking does not contribute significantly to the variability in nifedipine pharmacokinetics. However, the interaction between nifedipine and cimetidine, but not ranitidine, may be of clinical importance.

Adult↗
PubMed1987

Oxygenation and breathing pattern during phasic and tonic REM in patients with chronic obstructive pulmonary disease.

Oxygen desaturation in chronic obstructive pulmonary disease (COPD) occurs during sleep and is most marked in REM sleep. REM is not a homogeneous state, consisting of phasic REM (PREM) (REMs, myoclonic twitches) and tonic REM (TREM) (muscle atonia, desynchronized electroencephalogram). In normals, onset of PREM produces transient changes in breathing pattern with a decrease in respiratory amplitude and an increase in frequency, which produce reductions in oxygen saturation (SaO2). Because it is reasonable to expect such breathing pattern changes to cause more desaturation in COPD, and because systematic all-night studies of PREM and TREM have not been reported, we studied 18 patients with severe COPD [Forced expiratory volume in one second (FEV1) = 25.7 +/- 3.5 (SEM) % predicted] during sleep and monitored SaO2 and breathing pattern in PREM and TREM. PREM made up 19.7% of total REM (4.6% total sleep time) but was associated with 81.7% of the total REM desaturations of greater than 5% (57.9% of all sleep desaturations of greater than 5%). With PREM onset, breathing pattern changed 72.5% of the time, most often with a transient decrease in amplitude and increase in frequency. Even though 27.5% of PREM was not associated with changes in breathing pattern and many PREM segments were very short, we were still able to show highly significant SaO2 differences between PREM and TREM. Mean TREM SaO2 was 88.0 +/- 1.2%; mean PREM SaO2 was 86.6 +/- 1.4%, with mean nadir SaO2 for individual PREM segments falling to 84.8 +/- 1.5%. Mean awake SaO2 was 89.7 +/- 0.8%. We conclude that in COPD the transition from TREM to PREM is associated with breathing pattern changes and oxygen desaturation. Differences in breathing pattern with PREM onset may be related to different effects of PREM processes on respiratory neurons and diaphragm motor neurons.

Aged↗
PubMed1987

Dynamic in vivo response characteristics of three oximeters: Hewlett-Packard 47201A, Biox III, and Nellcor N-100.

Pulse oximeters (Biox III, Nellcor N-100) and a transmittance oximeter [Hewlett-Packard 47201A (HP)] were compared for SaO2 measurement and responsiveness during dynamic changes in arterial oxygen saturation and heart rate. Five sleep apnea syndrome patients were studied because they had large oscillations in SaO2 and heart rate in sleep. During sleep, each patient exhibited a series of rapid (18.0 +/- 8.3 s, mean +/- SD) oscillations in oxygen saturation (92.1 +/- 2.6% to 74.2 +/- 7.7%). Oxygen saturation measurements were sampled simultaneously from each oximeter by computer (at 2 Hz). Accuracy was assessed by comparing pulse and transmittance oxygen saturation measurements at the peak and trough of each apnea-related oscillation. Oximeter response was defined in terms of the "delay" or absolute time difference between the pulse oximeters and the transmittance oximeter for the determination of the peak and trough saturations. Linear regression analysis was used to establish accuracy and response relationships between pulse oximeter sensors (reusable ear, reusable digit, disposable digit, and disposable nasal sensors) and the transmittance oximeter sensor (reusable ear sensor). Pulse oximeter response delay was highly correlated with heart rate. Pulse oximeter SaO2 measurement and response characteristics varied considerably with sensor type (disposable, reusable) and sensor location (ear, nose, and digit). One must be aware of these differences in clinical and research application.

Adult↗
PubMed1987

Sleep in restrictive lung disease.

Restrictive lung disease patients exhibit a wide range of breathing and oxygenation abnormalities during sleep. The combination of degree of restriction, whether it is intrapulmonary or extrapulmonary, and confounding factors, such as obesity, age, and sex, will ultimately determine the degree of disturbed nocturnal physiology. The sleep literature is still sparse in most restrictive diseases. For patients with interstitial lung disease, the role of nocturnal oxygen in chronic established fibrosis, and also in acute alveolitis (e.g., farmer's lung, bird fancier's lung, etc.), has not been addressed. As fibrotic lung disease progresses, the degree of nocturnal desaturation and breathing dysrhythmias will progress. Changes in sleep architecture are likely related to the progression of the disease, but this is not known with certainty. Long-term evaluation of sleep and breathing in interstitial lung disease will give further insight into whether or not sleep changes are primary or secondary events. For kyphoscoliosis patients, again, we need more information on sleep as the thoracic deformity changes. In addition, the use of drugs (acetazolomide, medroxyprogesterone, and almitrine) and/or nasal CPAP to treat nocturnal desaturation needs to be assessed in a controlled fashion. In neuromuscular disease, the dynamics of gas exchange and sleep structure need to be defined in a larger group of patients. Factors such as degree of muscle weakness, degree of underlying lung diseases, and medications must be taken into consideration. Nocturnal hypoxemia may cause muscle weakness and fatigue, which in time, could cause more nocturnal hypoventilation and further hypoxemia. Supplemental nocturnal oxygen should be evaluated in this population.

Female↗
PubMed1987

The trans-hepatic extraction of nifedipine.

1. The trans-hepatic extraction of nifedipine during steady state infusion was studied in six patients undergoing cardiac catheterisation for suspected coronary disease. 2. Mean extraction ratio across the liver was 0.64 but hepatic clearance accounted for a mean of only 65% of total body clearance. 3. These results are consistent with the liver as the major site of metabolism of nifedipine, but also suggest that significant metabolism occurs outside the liver.

Adult↗
PubMed1987

The reduction of sulphinpyrazone and sulindac by intestinal bacteria.

1. Incubation of human or rabbit faeces with sulphinpyrazone gave greater reduction under anaerobic than under aerobic conditions. Reduction of sulindac by human faeces was more extensive than that of sulphinpyrazone. 2. Growth of mixed cultures of intestinal bacteria in nutrient media containing antibiotics produced a marked inhibition in their ability to reduce sulphinpyrazone. Sulphide formation was inhibited by metronidazole and lincomycin for human faeces and by tetracycline for rabbit faeces/caecal contents. 3. The formation of the sulphides of sulindac and sulphinpyrazone ex vivo was decreased in faeces from patients treated with metronidazole. Metronidazole, but not tetracycline, decreased the extent of reduction of sulphinpyrazone by rabbits in vivo. No reduction of either substrate occurred on incubation with ileostomy effluent. These data indicate that anaerobic intestinal bacteria are important in the reduction of these sulphoxide-containing drugs. 4. However, when incubated anaerobically with over 200 strains of bacteria isolated from human faeces, sulphinpyrazone was reduced by most of the aerobic but not the anaerobic organisms. Sulindac was reduced more extensively by the same aerobes and by some anaerobes. 5. The discrepancy between the apparent importance of anaerobes in vivo and in vitro may be due to their very large number present in the hind gut and to the production of an anaerobic environment suitable for the enzymic activity of other organisms, such as aerobes or facultative anaerobes.

Animals↗
PubMed1987

Medication in the elderly.

Medicine taking is common among elderly patients, especially in those over 75 years. A major problem is their increased rate of adverse drug reactions as a result of multiple drug therapy, altered pharmacokinetics, and variable response of the end organs or target tissues (pharmacodynamics). Some of these alterations have been well documented, especially alterations in excretion via the kidney. Nomograms exist which allow fairly accurate prediction of the required dosage adjustment and for some drugs measurements of their concentrations in blood can provide additional assistance in selecting an appropriate dose. However, for drugs which undergo metabolism, usually within the liver, alterations are more difficult to predict. In general, drugs like propranolol, which exhibit considerable first-pass metabolism, show a greater bioavailability in this age group and a slight prolongation of their half-lives. But other drugs, e.g. anti-pyrine, which have no significant first-pass metabolism and show a low rate of clearance from the asytemic circulation, exhibit little change in their pharmacokinetics with age. To date, studies of pharmacodynamic variation with ageing have been comparatively scant. Among those which have been documented are reduced beta-adrenoceptor sensitivity, increased effectiveness of the anticoagulant warfarin, and increased effects of a variety of benzodiazepines. Drug therapy in elderly patients should be kept simple and the number of drugs given simultaneously should be limited, and dosage may need to be reduced when a drug has a narrow therapeutic index or is excreted unchanged via the kidneys.

Aged↗
PubMed1986

The effects of food and posture on the pharmacokinetics of a biphasic release preparation of nifedipine.

The pharmacokinetics of a novel 20 mg biphasic release tablet of nifedipine were compared with the conventional 10 mg capsule and 20 mg sustained release preparations in healthy volunteers. The influence of food and posture on the pharmacokinetics of the biphasic tablet were studied. In the fasting state, the time to peak concentration of nifedipine was not significantly different between the 20 mg biphasic and 20 mg sustained release tablets, but plasma concentrations were higher between 2 and 4 h after the biphasic tablet. The terminal elimination half-lives of the two formulations were similar. In subjects who fed prior to nifedipine administration there was no significant difference between either the peak plasma concentration or terminal half-life of the biphasic tablet and two 10 mg capsules of nifedipine. When the biphasic preparation was given after a standard breakfast, the time to peak plasma concentration was significantly longer and the terminal half-life shorter than when given in the fasting state. The dissolution characteristics of the biphasic tablet were influenced by prior administration of food to an extent which may be of clinical significance during twice daily administration.

Delayed-Action Preparations↗
PubMed1986

A comparison of isoxicam pharmacokinetics in young and elderly subjects.

1 The pharmacokinetics of isoxicam have been compared in 57 volunteers with an average age of 31.3 years and 48 elderly subjects with an average age of 71.9 years. 2 Isoxicam was given in a single daily dose of 200 mg for up to 22 days. Similar plasma concentrations were obtained in the two age groups, average maximum concentrations being 39.7 mg l-1 in those under 65 and 38.1 mg l-1 in the elderly. There were no significant differences in the half-life which averaged 30.4 and 32.1 h respectively. 3 Approximately 9% of all those studied had half-life values in excess of 50 h. The results are consistent with the possibility of genetic polymorphism of isoxicam hydroxylation. 4 It is concluded that isoxicam is suitable for use in once daily dosage and that there are no clinically significant differences in its pharmacokinetics between young and elderly subjects.

Adolescent↗
PubMed1986

Knowledge of and attitudes to medicines in the Southampton community.

A 1 in 200 sample of the Southampton electorate was sent a postal questionnaire in January, 1984. Of the 740 adults surveyed, 443 (59.9%) returned completed questionnaires. One hundred and eighty-eight (42.4%) of those replying had been prescribed a medicine within the previous month. Two hundred and seventy-five respondents (62%) felt that not enough was explained about medicines by doctors or pharmacists. Consistent with this, was the fact that 37% were unaware of safe methods of disposal of leftover medicines. In addition, 112 of 154 (72.7%) people currently taking a prescribed medicine knew of no side-effects which could result from this. Eighty-three per cent of respondents thought an information leaflet would be helpful. Of nine items which previous authors had suggested should be included, seven were thought to be important by more than 75% of those replying. Although 54% of people wanted detailed information, 43% stated a preference for short, summarized points. We conclude that most patients need to have more information about prescribed medicines and they would welcome written leaflets. However, further work is necessary to determine the best format for such leaflets.

Adolescent↗
PubMed1985

Sulindac metabolism: the importance of an intact colon.

The pharmacokinetics of sulindac have been studied after a single 200 mg oral dose in six normal subjects and five patients with surgical ileostomies. The plasma concentration-time curves for sulindac were similar in both groups up to 12 hours after dosing, indicating similar absorption of the drug. Higher plasma concentrations of sulindac were found in normal subjects after 12 hours, but this late phase accounted for only 12% of the total AUC in the subjects. The sulfone metabolite showed a similar pattern, with no statistically significant difference in the total AUC, but in patients with ileostomy there was a halving of the AUC after 12 hours. Plasma concentrations of the active sulfide metabolite were similar in both groups up to 12 hours, but negligible concentrations were detected in the plasma of patients with ileostomy after 12 hours. Thus the AUC after 12 hours, which represented 55% of the total AUC in normal subjects, was reduced to only 7% in patients with ileostomy. The rate of reduction of sulindac in vitro by ileostomy effluent was only one hundredth that by normal feces. Our results suggest that the gut microflora are an important site of reduction of sulindac in man. Comparison of AUC values suggests that about half the total sulfide is formed by the gut bacteria, probably from sulindac excreted in the bile.

Absorption↗