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Biomedical subjects

D Perrier

Publications and source records attributed to D Perrier.

At least 19 recordsLinked to original sources
PubMed1991

Use of an isolated in situ canine lung perfusion model to evaluate dopamine clearance by the lung.

An isolated in situ lung perfusion model was used to assess dopamine clearance by the lungs in 12 dogs. The preparation consisted of a closed perfusion system in situ, in which systemic arterial blood supply was interrupted. Blood flow to the lungs was maintained at presurgery flow rates. The inflow was restricted to the lungs by the pulmonary arteries and outflow was limited to the pulmonary veins. Pulmonary artery pressure, temperature and pO2 were maintained at physiological levels. After confirmation of a stable base line, one of 3 doses (1, 2, or 5 micrograms/kg/min) of dopamine was infused over 30 min to achieve steady-state blood concentrations, then blood samples were drawn at specified times during and after the infusion. Dopamine plasma concentrations were analyzed by high performance liquid chromatography with electrochemical detection. Dose-dependent disposition of dopamine was observed in both plasma concentration-time profiles and in clearance (20.3 +/- 9.6 ml/min/kg at 5 micrograms/kg/min vs. 41.6 +/- 19.1 ml/min/kg at 1 micrograms/kg/min, P = 0.038). A sham experiment revealed that the blood in this experimental preparation contributed less than 10% to the total clearance of dopamine. This study revealed that our isolated in situ model is an excellent method to evaluate the role of the lungs in drug removal. Furthermore, it confirmed that the lungs contribute to the clearance of dopamine from the body.

Animals↗
PubMed1990

[Tachistoscopic reading of arabic words].

The authors study the tachistoscopic recognition of Arabic words in Arabic speakers. This study shows that Arabic words are read by Arabic speakers in the same way as French words by French speaking readers. Under such circumstances, the direction of reading appears to be less important than hemispheric specialisation.

Adolescent↗
PubMed1979

Digoxin-quinidine interaction Pharmacokinetic evaluation.

Several recent reports have shown that plasma concentrations of digoxin increase when quinidine is administered along with digoxin; the present study was designed to explore the pharmacokinetics of this digoxin-quinidine interaction in six subjects. The elimination half-life of digoxin, although variable, did not change appreciably (42 vs. 44 hours) when quinidine was administered. Other pharmacokinetic values were substantially reduced in the presence of quinidine: total body clearance (from 3.08 to 1.96 ml per minute per kilogram), renal clearance (from 1.64 to 1.09 ml per minute per kilogram) and volume of distribution (from 10.87 to 7.35 liters per kilogram). The results may be explained by the displacement of digoxin from binding sites in tissue by quinidine, causing a rise in the plasma concentration of digoxin. The reduction in renal clearance of digoxin may result also from inhibition of renal secretion of digoxin by quinidine.

Digoxin↗
PubMed1979

Pharmacokinetic properties of thiopental in two patients treated for uncontrollable seizures.

Thiopental was administered for seizure control in 2 patients with uncontrollable seizures. Serum samples were collected from each patient and assayed for thiopental, and the resulting serum concentration--time data were analyzed pharmacokinetically. The biologic half-life in both patients was significantly longer than previously reported values. Based on the limited number of patients studied, it would appear that half-life and volume of distribution increase with the degree of obesity, while clearance remains unchanged. These pharmacokinetic characteristics would be worthy of consideration in cases where there may be prolonged use of thiopental, eg., for the control of uncontrollable seizures.

Adolescent↗
PubMed1978

Dose tolerance and pharmacokinetic studies of L (+) pseudoephedrine capsules in man.

Dose tolerance and pharmacokinetic studies of pseudoephedrine sustained action capsules were performed in thirty-three adult male subjects who received either 120 mg or 150 mg capsules every twelve hours for seven consecutive days in a double-blind parallel design study. Although only one subject in the 150 mg group was discontinued prematurely from this study, a large number of side effects typical of CNS stimulation were seen. A placebo effect might account for a portion of these complaints, however symptoms evaluated as being due to drug were significantly more severe and persistent in the 150 mg group. Pulse rates showed a persistent and significant increase while systolic and diastolic blood pressure fell from the baseline values in both groups. A pharmacokinetic analysis of the pseudoephedrine plasma concentration-time data provided estimates of half-life and the volume of distribution/availability ratio. The values obtained were in good agreement with values reported by others. Half-life was not influenced by urine pH probably as a result of the narrow range of urine pHs observed in the subjects. Calculations of relative bioavailability suggest that the 120 mg capsule formulation has a 30% greater bioavailability compared to the 150 mg capsule.

Adult↗
PubMed1978

Plasma protein binding and distribution characteristics of drugs as indices of their hemodialyzability.

The dialysis clearance, plasma protein binding, and distribution (expressed as volume of distribution) characteristics of a drug were evaluated as predictive indices of the efficiency of hemodialysis in removing drug from the body. Dialysis clearance correlated poorly with the fraction of drug in the body removed by hemodialysis. The best predictive measure of hemodialysis efficiency was obtained by a nonlinear model relating the ratio of the percent of free drug in the plasma and the volume of distribution of the drug to the fraction removed. Knowledge of the binding and distribution characteristics of a drug provides insight into the dialyzability of a drug which in turn may assist in coming to decisions on the necessity of dose adjustments for patients on chronic hemodialysis and the rational use of hemodialysis in the treatment of drug intoxication.

Blood Proteins↗
PubMed1978

Prodrug approaches to enhancement of physicochemical properties of drugs IX: acetaminophen prodrug.

The synthesis, hydrolysis rate, and bioavailability of 1-(p-acetaminophenoxy)-1-ethoxyethane, an acetaminophen prodrug, are described. The prodrug is less soluble than acetaminophen and stable at neutral pH. However, in an acidic environment, the compound cleaves rapidly, generating acetaminophen. When both the prodrug and acetaminophen were administered to dogs in equivalent amounts, the blood acetaminophen levels were comparable.

Acetaminophen↗
PubMed1978

Digoxin disposition kinetics in dogs before and during azotemia.

The purpose of this study was to evaluate the disposition kinetics of digoxin after the administration of a single intravenous dose to the same dogs before and during azotemia. The digoxin plasma concentration-time data were fitted to a multicompartment model using nonlinear regression analysis. During azotemia, the biological half-life of digoxin was prolonged in six of seven dogs, while digoxin renal clearance, body clearance and apparent volume of distribution were significantly decreased. There was a corresponding increase in the apparent volume of the "central" compartment of digoxin. Approximately 45% of a digoxin dose was excreted by the kidney in these animals indicating a substantial nonrenal component to digoxin elimination in the dog. This nonrenal elimination did not change during azotemia, despite a decrease in renal clearance by 61%.

Animals↗
PubMed1978

Kinetics of pharmacologic response to cocaine.

Cocaine plasma concentration-response-time data obtained from the literature were analyzed by pharmacokinetic methods. The plasma concentration-time data yield an elimination half-life of approximately 1 hour and the data suggest that only about 20% of an oral dose of cocaine is absorbed intact into the systemic circulation. Response, as assessed by means of a relative "high" rating scale, declined linearly with time as predicted by theory. The rate of decline of response was found to be 0.0221 "high"/min. The rate of decline of response is a function of the apparent first-order elimination rate constant (K) of the drug and the slope of the response-log plasma concentration curve (m). A value for m of 4.2 "high" was calculated from the response-time data which agreed well with a value of 3.9 "high" for m determined from the slope of the response-log plasma concentration curve.

Cocaine↗
PubMed1977

Evaluation of a charcoal-sorbitol mixture as an antidote for oral aspirin overdose.

The preparation of charcoal in a 70% sorbitol solution results in a suspension that is more palatable and less gritty than an aqueous slurry of charcoal. Although the charcoal-sorbitol mixture may be slightly less effective in reducing the extent of aspirin absorption compared with a charcoal slurry, it may prove to be of particular value in those cases where acceptance of a charcoal slurry presents a problem.

Adult↗
PubMed1976

Influence of "thickening" agents on the antidotal efficacy of activated charcoal.

The addition of "thickening" agents such as bentonite and carboxymethylcellulose to activated charcoal slurries considerably improves the palatability of this antidote yet does not reduce the efficacy of the activated charcoal in reducing the gastrointestinal absorption of aspirin. Flavoring of such preparations may further enhance this palatability.

Adult↗
PubMed1976

Maintenance of therapeutic phenytoin plasma levels via intramuscular administration.

A parenteral dosing regimen was designed for the immediate attainment and maintenance of therapeutic plasma levels of phenytoin in patients requiring anticonvulsant therapy, but not able to tolerate oral medication. An intravenous dose of 10.7 mg/kg body weight infused at a rate of 25 mg/min immediately followed by an intramuscular dose of 12.7 mg/kg body weight were administered initially. This was followed by daily intramuscular maintenance doses, generally 8.6 mg/kg body weight, until oral medication could be tolerated. Due to variability between subjects, primarily in metabolism, the predicted maintenance doses had to be adjusted in approximately one third of the patients. This regimen for the dosing of phenytoin was evaluated in 98 patients and consistently yielded therapeutic levels.

Administration, Oral↗
PubMed1976

Gas-chromatographic quantitation of theophylline in small volumes of plasma.

We describe a rapid procedure for quantitating theophylline in 100-mul plasma samples by use of a gas-liquid chromatograph equipped with a flame ionization detector. This methos is especially useful for monitoring theophylline concentrations in serum or plasma of infants, because sufficiently large blood samples can be readily obtained from a heel prick. The method is specific for theophylline in the presence of caffeine, theobromine and phenobarbital. For plasma concentrations equal to or greater than 5 mg/liter the average daily coefficient of variation was less than 7% while the coefficient of variation from day to day was less than 11%. The same approach can also be used to measure concentrations of phenobarbital in small volumes of plasma or serum, and is readily adapted to determination of theophylline and phenobarbital in larger samples.

Amobarbital↗