Biomedical subjects

H G Giles

Publications and source records attributed to H G Giles.

43 records · Page 3Linked to original sources

PubMed1978

Influence of age and previous use of diazepam dosage required for endoscopy.

In 19 patients (10 men and 9 women) a 22-fold variation was observed in the intravenous dose of diazepam necessary as preparation for endoscopy (median dose, 20 mg; range, 5 to 110 mg). Analysis of plasma samples for diazepam and N-desmethyldiazepam revealed that the clinical response did not relate to the rate or character of initial drug distribution. There was a high correlation (r = 0.96) between the dose and the plasma concentration 10 minutes after administration. Users of diazepam displayed tolerance to its pharmacologic effects, requiring a significantly larger (P less than 0.05) dose than nonusers (median doses, 35.0 mg and 14.5 mg respectively). Older patients required less than younger patients (r = -0.54, P less than 0.05). The variation between individuals in the dose of diazepam required as preparation for endoscopy cannot be explained by variation in drug disposition but instead reflects previous diazepam use, age and probably differences in sensitivity at the site or sites of drug action.

Adult↗

PubMed1978

Interaction of disulfiram with benzodiazepines.

The disposition of chlordiazepoxide (50 mg, intravenously), diazepam (0.143 mg/kg, orally), and oxazepam (0.429 mg/kg, orally) were studied in normal and alcoholic men before and after chronic disulfiram administration. Decreases in the plasma clearance of chlordiazepoxide (54%, p less than 0.05), diazepam (41%, p less than 0.05), and their active N-desmethyl metabolites were observed. Oxazepam has no important active metabolites and its net disposition is minimally altered by disulfiram. Oxazepam disposition is unaffected by age and liver disease. These considerations together with that of the short half-life of oxazepam (median, 6.1 hr) suggest that oxazepam may be the drug of choice if benzodiazepine therapy is used for patients taking disulfiram.

Adult↗

PubMed1978

Binding of drugs to ion-exchange resins in simulated gastric fluid.

The binding of 13 frequently abused drugs to two ion-exchange resins was studied in simulated gastric fluid. The results were compared with those previously obtained with activated charcoal as the adsorbent. The ion-exchange resins adsorbed the drugs more slowly than activated charcoal, and the binding capacities of the resins were inferior. These ion-exchange resins are unlikely to be very useful in removing drugs from the stomach.

Adsorption↗

PubMed1977

Diazepam actions and plasma concentrations following ethanol ingestion.

In eight normal volunteers, the combination of ethanol (0.5 g/kg) and diazepam (10 mg) administered orally produced a greater decrease in motor performance on a pursuit rotor than diazepam alone. The pharmacologic effect of diazepam was enhanced by 73% and this potentiation was associated with significantly greater diazepam concentrations (p less than 0.01) than after diazepam alone. The failure to observe any increase in the concentrations of the principal metabolite, N-desmethyl diazepam, during the period of enhanced pharmacologic effect precludes any change in the demethylating metabolic process as being responsible. The data suggest (0.10 greater than p greater than 0.05) a trend to a smaller volume of distribution of diazepam when ethanol is administered prior to diazepam ingestion. The subjects showed acute tolerance to the effects of diazepam. Lower plasma concentrations on the ascending side of the plasma diazepam concentration versus time profile were linked with the same pharmacologic responses associated with a greater drug concentration on the descending portion, of the same curve.

Adolescent↗

PubMed1976

Markers for detection of supplementation in narcotic programs--deuterium-labeled methadone.

Specific deuterium labeling of methadone and use of gas chromatography-mass spectroscopy technique permits rapid and quanitative determination of the ratio of the labeled to unlabeled drug in body fluids. A trideuertiomethadone (methadone-d3) was shown to have exactly the same analgesic activity and toxicity in mice as methadone. The rates of absorption, distribution, and excretion of methadone-d3 and methadone were identical in rats. These observations suggest that methadone-d3 may be used as an in vivo marker for monitoring methadone intake of patients, and thus may improve the effectiveness of methadone treatment programs.

Animals↗

PubMedDate not supplied

Diazepam and N-desmethyldiazepam in saliva of hospital inpatients.

Saliva samples were obtained from 25 hospital inpatients (14 males, 11 females, aged 19 to 79 years) taking diazepam (6 to 45 mg) daily. Despite interindividual variations in pharmacokinetics, a correlation was found between both dose and salivary diazepam concentration (r = 0.54, P less than 0.01) and dose and salivary N-desmethyldiazepam concentration (r = 0.78, P = 0.01). The correlation between the salivary concentration of diazepam and that of its metabolite is good (r = 0.76, P less than 0.01). The slope of this linear regression, 1.58, reflects the relative clearances of the metabolite and parent drug and agrees with the theoretical value, 1.60, obtained by calculation using known plasma pharmacokinetic and protein-binding parameters. There is a weak linear correlation of steady-state salivary benzodiazepine (drug and metabolite) concentration per milligram dose and age (r = 0.37, P less than 0.01).

Adult↗

PubMedDate not supplied

Disposition of intravenous propylthiouracil.

Propylthiouracil was administered to 10 healty, male volunteers by a short intravenous infusion. Plasma and urinary drug concentrations were determined by a specific high-performance liquid chromatography assay, and protein binding was determined by equilibrium dialysis. After infusion, the plasma concentrations declined biexponentially, and the following median parameters (and ranges) were determined: clearance 273.5 ml/min (159.5-377.8 ml/min); free drug clearance, 1537.7 ml/min (985.9-1927.3 ml/min); apparent volume of distribution, 28.0 liters (22.7-44.4 liters); apparent elimination half-life, 1.28 hr (0.88-2.05 hr); k21, 3.12 hr-1 (1.06-5.36 hr-1): alpha 7.34 hr-1 (1.94-25.03 hr-1): Vc 9.40 liters (5.16-18.58 liters). In urine, only 1.28 per cent (0.03-2.01 per cent) of the administered dose was recovered over 24 hours as unchanged drug. The ratio (1.2 per cent) of urinary clearance (3.2 ml/min) to plasma clearance is far less (P less than 0.001) than the free fraction in plasma (median 18.2 percent, range 16.2-20.2 per cent) and this suggests that there is significant renal tubular reabsorption of propylthiouracil. In healthy subjects, both intraindividual and interindividual variation of protein binding is modest, and free drug clearance can be predicted from total drug clearance (y =- 257.6 + 4.56x, r = 0.95, P less than 0.001).

Adult↗