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Biomedical subjects

D Perrier

Publications and source records attributed to D Perrier.

At least 55 records · Page 3Linked to original sources
PubMed1980

Effect of dose on phenytoin absorption.

To determine the effect of dose on phenytoin bioavailability, a single intravenous 15-mg/kg dose, single oral doses of 400, 800, and 1,600 mg, and 1,600 mg in divided doses (400 mg every 3 hr) were given to six healthy male subjects. Values of Vmax (maximum elimination rate) and Km (serum concentration at which rate of elimination is one half the maximum rate) from the intravenous dose were used to determine the extent of absorption. Although no statistically significant difference in extent of phenytoin absorption was detected, the time to reach maximum phenytoin serum concentrations increased from 8.4 hr for the 400-mg dose and 13.2 hr for the 800-mg dose to 31.5 hr for the 1,600-mg dose. After the 400, 800, and 1,600-mg doses and 1,600-mg divided doses, the serum concentration peaks were 3,9, 5.7, 10.7, and 15.3 mg/l. It is suggested that the prolonged, but complete, absorption of large phenytoin doses is due to slow dissolution and continued absorption from the colon. Due to prolonged absorption of phenytoin, it may be necessary to use larger oral than intravenous loading doses to achieve the same maximum phenytoin serum concentrations.

Administration, Oral↗
PubMed1980

Kinetic evaluation of the propranolol-quinidine combination.

The kinetics of quinidine and propranolol, administered singly and in combination, were evaluated in 5 healthy subjects. The orally administered doses resulted in plasma concentrations within the therapeutic range. For each drug the average steady-state plasma concentration, maximal plasma concentration, and time of maximum plasma concentration were not altered by the presence of the other drugs. This study shows no kinetic interaction between quinidine and propranolol in normal subjects.

Adult↗
PubMed1980

Metabolism and rate of elimination of digoxigenin bisdigitoxoside in dogs before and during chronic azotemia.

The purpose of this study was to evaluate the metabolism and rate of elimination of digoxigenin bisdigitoxoside (bis) before and during chronic azotemia in dogs. Bis was eliminated primarily by nonrenal mechanisms. The half-life of bis was 18.5 hr, compared to 31.6 hr for digoxin, and was not significantly increased in azotemic dogs. The oral bioavailability of bis in azotemic dogs relative to an intravenous dose was approximately 46%.

Animals↗
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↗