Search PubMed⌕ Search

Biomedical subjects

C F George

Publications and source records attributed to C F George.

At least 109 records · Page 6Linked to original sources
PubMed1985

Pharmacology of propranolol in patients with cirrhosis and portal hypertension.

Ten patients with cirrhosis and protal hypertension received an initial 20 mg oral test dose of propranolol and subsequently 160 mg of a slow release preparation, orally, each day for seven days. Protein binding, serial plasma propranolol concentrations and effects on heart rate were studied. Protein binding was slightly reduced (mean 85%, range 78.9-88.1%) compared with four normals (mean 87.9%). In patients with severe liver disease (serum albumin less than 30 g/l) propranolol remained detectable in plasma 24 hours after the single 20 mg dose and high steady state concentrations (mean 266.5 ng/ml, range 84-406) were observed during regular dosing. At steady state there was a significant correlation between log total plasma propranolol concentrations and the percentage fall in heart rate (r = 0.659, p less than 0.05). We suggest that in patients with severe liver chronic disease (serum albumin less than 30 g/l), propranolol therapy should be initiated in hospital. The starting dose should be low (20 mg of the conventional formulation tds or 80 mg of the slow release preparation daily) and that regular monitoring of the heart rate should be carried out.

Aged↗
PubMed1985

Sleep and control of heart rate.

The heart rate in normal humans is determined by many factors. Assuming a normal hemoglobin concentration, left ventricular function, and metabolic rate, respiration, and its effects, along with autonomic nervous activity, appear to influence heart rate the most. Hypoxia and hypercapnia both increase heart rate during wakefulness and probably do the same during sleep. The hypoxic response is dependent on information from lung inflation and the carotid bodies. Respiratory rate, within limits, will determine the amplitude of the well-known (respiratory) sinus arrhythmia. During sleep, a distinct pattern of heart rate response and its respiratory arrhythmia are seen for each stage of sleep and are related to the level of autonomic nervous system activity during wakefulness. Blood pressure follows the same trend as heart rate during sleep, and changes in cardiac output and total peripheral vascular resistance are variable during sleep, but there is no consensus of opinion about the direction of these changes. Rhythm disturbances are predominantly those of bradyarrhythmias, exaggerated sinus arrhythmias, and transient AV block, which are probably occurring in REM sleep.

Arousal↗
PubMed1984

The first pass metabolism of nifedipine in man.

Oral administration of nifedipine (20 and 30 mg tablets) to six volunteers was associated with a bioavailability of 0.43 and the presence of its nitropyridine analogue in the plasma. This metabolite was present in only trace amounts in samples taken from the same volunteers following i.v. administration of nifedipine. The peak plasma concentrations and area under the plasma concentration-time curve suggest that the nitropyridine analogue is a major, first pass, metabolite of nifedipine.

Administration, Oral↗
PubMed1984

The site of reduction of sulphinpyrazone in the rabbit.

Comparison of oral and i.v. administration of sulphinpyrazone (10 mg/kg) to rabbits showed that the oral route was associated with an incomplete bioavailability and a six-fold greater formation of the active sulphide metabolite. The bile was an important route of elimination of unchanged sulphinpyrazone in rabbits (18% of an i.v. dose in four hours). Only small amounts of the sulphide appeared in the bile after i.v. administration. Pretreatment with oral antibiotics decreased the area under the plasma concentration-time curve (AUC) for the sulphide but increased that of the parent drug. Excretion of the p-hydroxysulphide metabolite in urine was decreased 30-fold by antibiotic treatment. The contents of the caecum showed the greatest capacity for sulphinpyrazone reduction in vitro. The liver possessed a slight ability to reduce sulphinpyrazone in vitro under anaerobic, but not aerobic, conditions. The gut bacteria are the main site of reduction of sulphinpyrazone to the active sulphide metabolite in the rabbit. These findings contrast with those obtained for sulindac which was reduced extensively under both aerobic and anaerobic conditions by rabbit-liver soluble fraction in vitro. The sulphide metabolites of both sulphinpyrazone and sulindac were oxidized to the parent drug by rabbit-liver microsomes.

Administration, Oral↗
PubMed1984

Role of the gut flora in the reduction of sulfinpyrazone in humans.

Peak plasma concentrations of sulfinpyrazone occurred about 2 h after administration of a single oral dose (200 mg tablet) to 11 normal volunteers. In contrast, the peak concentrations of the active sulfide metabolite occurred 15 h after dosing. Concurrent oral administration of metoclopramide with sulfinpyrazone resulted in a 4-fold decrease in the time to peak sulfide concentrations and a 3-fold increase in the amounts formed. A slow release formulation showed a low, variable bioavailability, but the proportion of sulfide was 3-fold higher based on the ratio of the area under the plasma concentration-time curve of the sulfide to that of the parent compound. Intravenous administration of sulfinpyrazone demonstrated that the tablets had a high bioavailability (about 90%), and the time to peak plasma concentration of the sulfide and the amount formed were similar to those seen after oral administration. Patients who had undergone surgical removal of the distal part of the intestine had normal plasma concentrations of sulfinpyrazone, but negligible amounts of the sulfide, after oral administration of sulfinpyrazone. The ileostomy effluent of such patients showed little ability to reduce sulfinpyrazone in vitro, in contrast to the extensive reduction detected with normal feces. These data demonstrate that the hind gut microflora are the principal and possibly the only site of reduction of sulfinpyrazone to its active sulfide metabolite in humans.

Administration, Oral↗
PubMed1983

Prescription information leaflets: a pilot study in general practice.

Leaflets containing information about medicines were issued to 56 patients prescribed penicillins and 43 patients prescribed non-steroidal anti-inflammatory drugs. The patients were interviewed between four and 10 days later and their responses compared with those of 65 patients prescribed penicillin and 33 prescribed nonsteroidal anti-inflammatory drugs who did not receive a leaflet. Patients who received a leaflet were more likely to be completely satisfied with their treatment and with the information they had been given. They were also more likely to know the name of their medicine and much more aware of potential unwanted effects. Although there was no evidence that knowledge increased the incidence of adverse effects, when these did occur they were more likely to be recognised as being due to the medicine. Further studies of other leaflets are warranted, including leaflets for drugs that are taken long term.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1983

The absorption and conjugation of methyldopa in patients with coeliac and Crohn's diseases during treatment.

The absorption and elimination of a single 500 mg dose of methyldopa has been studied after oral administration to 10 normal volunteers, 10 patients with coeliac disease, who were on a gluten-free diet, and to five patients with Crohn's disease. In patients with Crohn's disease the percentage of the dose recovered in urine (24%) was about one-half of normal (50%). This decreased absorption was associated with reduced plasma concentrations of both free and conjugated methyldopa and a decreased pharmacological response. In patients with coeliac disease the percentage of dose recovered in urine (43%) was similar to normals, indicating a normal absorption of the drug. However, the plasma concentrations of both free and conjugated methyldopa were significantly higher than normal, although there was no increase in drug-related effects. These findings confirm the importance of using indices other than drug plasma concentrations in the assessment of bioavailability in disease states.

Adult↗
PubMed1983

Acebutolol pharmacokinetics in renal failure.

Acebutolol was administered orally in a single dose of 200 mg to 17 individuals whose renal function varied markedly. The plasma half-life and elimination rate constant for acebutolol showed a four-fold variation but these did not correlate with the degree of renal impairment. However, there was a good correlation between the renal clearance of creatinine and that of acebutolol (P less than 0.001). The half-life and elimination rate of the acetyl metabolite, diacetolol, were subject to 10-fold inter-individual variability which correlated significantly with the creatinine clearance and serum creatinine concentration. The AUC for the acetyl metabolite showed a 40-fold individual variation which also correlated with renal function. It is concluded that renal elimination is the principal route of excretion for diacetolol but not the parent compound, acebutolol.

Acebutolol↗
PubMed1982

The role of the gut flora in the reduction of sulphinpyrazone in the rat.

Sulphinpyrazone underwent both reduction to a sulphide and oxidation to a sulphone after parenteral administration to normal Wistar rats. Oral administration was associated with a bioavailability of about 75% and with a 3-fold greater formation of the sulphide. However, no sulphide was detected in the plasma after oral administration of sulphinpyrazone to germ-free (BD/X) rats or normal rats treated with oral antibiotics. In vitro studies showed that the major site of reduction of sulphinpyrazone was the contents of the hind gut with little activity detected in the liver or other tissues. The sulphide was oxidised in vivo to sulphinpyrazone and small amounts of sulphone, while the latter underwent only slight reduction to sulphinpyrazone, but did not give detectable levels of the sulphide. These data suggest that the gut microflora are the main site of reduction of sulphinpyrazone in the rat in vivo.

Anaerobiosis↗