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Biomedical subjects

W D Hooper

Publications and source records attributed to W D Hooper.

At least 91 records · Page 5Linked to original sources
PubMed1975

Plasma protein binding of carbamazepine.

The binding of carbamazepine to the proteins of human plasma has been studied using ultrafiltration techniques. In vitro studies at 37 degrees C showed the relation between concentration of unbound drug and total drug to be linear through the range of total concentration of 5 to 50 mug/ml. The per cent unbound drug increased slightly as concentration increased. There was little difference between the extent of binding at 4 degrees C and 20 degrees C, but more carbamazepine was unbound at 37 degrees C. Under in vitro conditions, 6 other anticonvulsants, and aspirin, were tested individually, each at high therapeutic or toxic concentration, and shown not to displace carbamazepine from plasma proteins to a significant degree. The extent of binding of carbamazepine in vivo was determined in a total of 54 plasma samples collected from treated patients; 26.9 plus or minus SD 9.4 percent of the drug was unbound. In blood samples from 23 of these patients, the red cell concentration of carbamazepine averaged 38.3 plus or minus SD 17.9 percent of the plasma concentration. The effects of hepatic and renal diseases on the carbamazepine binding capacity of plasma proteins were assessed by comparing the binding capacity of plasma from disease persons with that from normal subjects. There was no significant difference in binding capacity between plasma from patients with renal disease and that from normal subjects. However, the plasma from patients with hepatic disease bound a slightly lower percentage of carbamazepine than did normal plasma (p smaller than 0.05). This alteration did not correlate with changes in any of 15 biochemical parameters measured in these patients. The clinical significance of these results is discussed.

Adolescent↗
PubMed1975

Decreased capacity to metabolize diphenylhydantoin in a patient with hypersensitivity to warfarin.

A 48 year old man with normal hepatic function presented with abnormally prolonged bleeding following orally administered warfarin. Warfarin and diphenylhydantoin are known to be hydroxylated in the liver. To investigate the possibility of the patient having a metabolic (hydroxylating) defect, his ability to metabolize diphenylhydantoin was studied, as it would have been unethical to administer warfarin again. Parallel studies were carried out on two healthy subjects as a basis for comparison. On three separate occasions the elimination half-life for diphenylhydantoin in the patient (158, 87, 72 hours) was significantly longer than those obtained in the normal subjects (31 and 32 hours). This difference was most probably due to decreased hydroxylation of diphenylhydantoin to 5-(p-hydroxy-phenyl)-5-phenylhydantoin since his urinary elimination of this substance was demonstrated to be significantly less than that of the normal subjects. The results suggest that this patient had a reduced capacity to hydroxylate diphenylhydantoin, and this defect in liver hydroxylation may explain his increased sensitivity to warfarin.

Half-Life↗
PubMed1975

The bioavailability of carbamazepine.

Two aspects of the correlation of plasma carbamazepine level with drug dose in patients taking carbamazepine tablets indicated the possibility that the drug may be incompletely and variably absorbed from the alimentary tract of man. To investigate this possibility, pharmacokinetic studies were undertaken in six volunteers, who were given increasing single doses of carbamazepine in tablet form at appropriate intervals. These studies gave evidence of slow, and probably incomplete, absorption of carbamazepine. After administration of carbamazepine in a specially-prepared solution to 5 of the subjects, rapid absorption of the drug occurred, and in 4 subjects more drug was absorbed than when the same normal dose was given as tablets. It was concluded that the pharmaceutical formulation of carbamazepine tablets limits the bioavailability of the drug, and that problems may arise if the bioavailability of the drug is to be increased.

Biological Availability↗
PubMed1974

Buccal absorption of ergotamine.

The rate of disappearance of ergotamine from the mouth after buccal administration has been studied in seven subjects. Allowance has been made for non-absorptive losses of the drug due to experimental technique. The absorption of ergotamine across the buccal mucosa appears to be a passive process, pH-dependent but independent of ergotamine concentration or the simultaneous presence of caffeine. Because of the low solubility of ergotamine at the pH of saliva, it is unlikely that therapeutically useful amounts of the drug would have absorbed across the buccal mucosa even after the drug had been in the mouth for five minutes.

Absorption↗
PubMed1972

Effect of a delayed-action phenytoin preparation on blood phenytoin concentration.

In a cross-over study in a group of epileptic patients it was shown that replacement of the evening dose of an ordinary phenytoin preparation with the same phenytoin dose in a delayed-action preparation produced no significant change in the next morning's mean blood phenytoin concentration. However, replacement of the entire daily dose of an ordinary phenytoin preparation with the delayed-action preparation did increase mean blood phenytoin levels after some days, possibly because the latter preparation contained an additional 6% active drug, as compared with the former. In most circumstances, it seems doubtful if the delayed-action preparation offers any advantage over ordinary phenytoin in treating epilepsy.

Chromatography, Gas↗
PubMed1972

Effect of dosage increments on blood phenytoin concentrations.

Blood phenytoin (diphenylhydantoin) concentrations were measured after each dosage change in 12 epileptic patients who were given increasing oral doses of phenytoin. In each of these patients a dosage increment beyond the dosage that produced a blood phenytoin level of 6-9 μg/ml. caused a disproportionately great increase in the blood concentration of drug. This effect might be expected if the limit of the body's capacity to metabolize phenytoin were being reached. As oral dosages were increased in one patient, measurements of the rate of urinary excretion of phenytoin metabolite showed that the phase of rapid rise in blood phenytoin concentration coincided with a failure to increase the rate of phenytoin metabolite excretion. Awareness of the non-linear relation between oral dose and blood concentration of phenytoin in the individual patient, and realization that the phase of rapid rise in blood phenytoin concentration occurs through the `therapeutic' range of 10-20 μg/ml., is of importance to those who use blood phenytoin levels as a guide to the adequacy of anticonvulsant therapy.

Administration, Oral↗