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Biomedical subjects

C Knott

Publications and source records attributed to C Knott.

43 records · Page 3Linked to original sources
PubMed1985

Epidural fentanyl in labour. An evaluation of the systemic contribution to analgesia.

In a randomized double-blind trial in the first stage of labour, 20 patients given fentanyl 80 micrograms in the epidural test dose of bupivacaine, were compared with 20 patients receiving an intravenous infusion designed to produce comparable plasma fentanyl concentrations, at the same time as their epidural test dose. Despite slightly higher plasma fentanyl concentrations in the intravenous fentanyl group, epidural fentanyl produced analgesia which was more complete, more rapid in onset and slightly longer lasting. Supplementary doses of bupivacaine were needed to produce analgesia in 75% of the intravenous and 30% of the epidural fentanyl group. It is clear that epidural fentanyl produces satisfactory pain relief when added to the epidural test dose, but that the presence of fentanyl in the systemic circulation makes a negligible contribution to analgesia.

Adult↗
PubMed1984

The place of saliva in antiepileptic drug monitoring.

It has previously been shown that saliva phenytoin concentration bears a constant relationship to plasma free concentration whether protein binding of phenytoin is normal or disturbed by other drugs, pregnancy, renal failure, or hypoalbuminaemia. The present work examines the relationship between saliva (S), plasma free (F), and plasma total (P) concentrations of other anticonvulsants in 100 epileptic patients. Mean S/P ratios were for phenobarbitone 0.37 (r = 0.95), primidone 0.95 (r = 0.87), and carbamazepine 0.27 (r = 0.94). A highly significant correlation of S with F was found for these drugs, more significant than the correlation of S with P for carbamazepine in patients receiving multiple anticonvulsant drugs. Saliva valproate, however, had no predictive value for P or F. No binding to saliva proteins was demonstrated for any drug. Data for in vitro binding to plasma proteins was in good agreement with ex vivo data. Saliva is therefore a valid medium for monitoring treatment with phenobarbitone, primidone, and carbamazepine, as well as phenytoin.

Adolescent↗
PubMed1984

Do saliva concentrations predict plasma unbound theophylline concentrations? A problem re-examined.

On the assumption that plasma unbound drug concentrations are therapeutically active, the value of saliva concentrations in predicting plasma unbound theophylline concentrations was investigated in 25 ambulatory adults (aged 27 to 84 years) receiving theophylline (225-1350 mg aminophylline daily) for asthma or chronic bronchitis. Plasma samples from all patients were ultrafiltered, and the plasma unbound theophylline (F) concentrations were compared with the corresponding total plasma (P), citric acid stimulated saliva (S) and non-stimulated saliva (Ns) theophylline concentrations. Plasma unbound theophylline concentrations correlated significantly with P (r = 0.97) and S (r = 0.973), but less well with Ns (r = 0.883), emphasising the benefit of saliva stimulation. The ability of S to predict F theophylline concentrations was assessed using the mean ratio of 0.7297. In 92% of the patients, predicted F concentrations were within +/- 1 microgram/ml of the measured concentrations. Similarly, using the mean F/P ratio of 0.418, predicted P were within +/- 1 microgram/ml of obtained P in 84% patients, and using the mean S/P ratio of 0.568, predicted P were within +/- 1 microgram/ml of obtained P in 81%. An accuracy of +/- 1 microgram/ml in estimating F from S concentrations would be sufficient to indicate appropriate dose adjustments, and we therefore advocate the use of stimulated saliva samples for routine monitoring of theophylline therapy.

Adult↗
PubMed1983

Epidural versus intramuscular fentanyl. Analgesia and pharmacokinetics in labour.

In a randomised double blind trial, 36 patients in the first stage of labour received either epidural or intramuscular fentanyl at the same time as the epidural test dose of bupivacaine. Analgesia was more rapid in onset and more complete in the epidural fentanyl group. Supplementary doses of bupivacaine were required within the first hour in 62% of the intramuscular fentanyl group compared with only 16% in the epidural group. Plasma fentanyl concentrations showed wide interindividual variation, but after epidural fentanyl the peak occurred earlier. There was no correlation between analgesia and plasma fentanyl concentration, and epidural fentanyl produced superior analgesia but a systemic contribution to this effect cannot be ruled out.

Adult↗
PubMed1982

Phenytoin-valproate interaction: importance of saliva monitoring in epilepsy.

Sodium valproate is often used with phenytoin when epilepsy cannot be controlled by a single drug. Sodium valproate depresses phenytoin protein binding and so invalidates plasma phenytoin monitoring as a means of determining precise phenytoin dosage requirements. Plasma and saliva phenytoin and plasma valproate concentrations were measured in 42 patients with epilepsy receiving both drugs. Phenytoin protein binding was also measured by ultrafiltration in 19 of these patients and 19 patients taking phenytoin alone. Saliva phenytoin concentration bore the same close correlation to unbound (therapeutically active) phenytoin in patients receiving both drugs as it did in patients receiving phenytoin alone, whereas plasma total phenytoin did not. The same therapeutic range for saliva phenytoin (4-9 mumol/1; 1-2 microgram/ml) was therefore valid in both groups. The depression of phenytoin binding was directly related to the plasma concentration of valproate both in random samples taken from the 42 patients and in samples taken throughout the day in two of these patients. This was confirmed in vitro. Even when the concentration of valproate is known the degree of binding cannot be predicted. Saliva rather than plasma monitoring of phenytoin treatment is therefore valuable in the presence of valproate and with reduced phenytoin binding from any cause.

Adolescent↗
PubMedDate not supplied

Placental transfer of anticonvulsants in the rabbit: the effect of maternal protein binding and fetal flow.

The fetal-to-maternal ratios of carbamazepine, antipyrine and phenytoin are principally determined by maternal protein binding, though greater lipid solubility may enhance the transfer of valproate compared to that of other drugs at high flows. Placental clearance of all anticonvulsants showed flow-dependent characteristics. This is in line with our findings for basic drugs.

Animals↗