Search PubMed⌕ Search

Biomedical subjects

D S Sitar

Publications and source records attributed to D S Sitar.

At least 127 records · Page 7Linked to original sources
PubMed1980

Effect of diet and drugs on the qualitative and quantitative distribution of cytochromes P-450 in rat liver.

Male Sprague-Dawley rats were fed either Purina chow or a nutritionally adequate liquid control diet containing either 4 or 38% of the total caloric intake as fat. The hepatic cytochromes -450 were induced in these animals either by the administration of phenobarbital, beta-naphthoflavone, or isocaloric replacement of the carbohydrate of the liquid diets by ethanol at a level of 36% of total calories for 4 or 6 weeks. Three distinct groups of cytochromes P-450 could be efficiently separated by ion-exchange chromatography of microsomal preparations from these rats. The concentration of each group of cytochromes P-450 was markedly affected by variations in lipid and carbohydrate content of the diet as well as by administration of drugs.

Animals↗
PubMed1979

Amantadine kinetics in healthy young subjects after long-term dosing.

We investigated the disposition of amantadine in 13 healthy, young adults after long-term dosage. Doses of 25, 100, or 150 mg, randomly allocated, were taken at 12-hr intervals in syrup for 31 doses. A 1-compartment open model and complete bioavailability were assumed. Absorption rate was variable with peak concentrations in plasma occurring at 1 to 12 hr. Since the calculated area under the plasma concentration against time curve was proprotional to it, relative bioavailability was independent of dose at steady state. As the dose increased, the apparent volume of distribution decreased. Intra- and intersubject variations in trough plasma drug concentrations at steady state were less than triple for equivalent doses. Elimination of drug from plasma was consistent with a first-order process. Plasma half-lifes (t1/2s) ranged from 10.2 to 31.4 hr and were independent of dose or creatinine clearance. The ratio of renal drug clearance to creatinine clearance ranged from 1.26 to 14.97, suggesting substantial renal tubular secretion. The median ratio of plasma drug clearance to renal drug clearance approached unity.

Adult↗
PubMed1978

Pharmacokinetic disposition and protein binding of furosemide in newborn infants.

Using a one-compartment model, the pharmacokinetic disposition of furosemide was studied in eight premature and term neonates with fluid overload. Following a single intravenous injection of furosemide (1 to 1.5 mg/kg), multiple blood samples were obtained from a heelstick or an arterial catheter and analyzed for furosemide by gas liquid chromatography. The mean (+/- SE) apparent volume of distribution was 829.2 +/- 118.9 ml/kg; t1/2 was 7.7 +/- 1.0 hour; elimination rate constant was 0.102 +/- 0.013/hour and plasma clearance was 81.61 +/- 14.98 ml/kg/hour. Compared to the disposition of furosemide in normal adults. AVd is almost fourfold greater in the neonate with an eightfold prolongation in plasma t1/2, an eightfold decrease in Ke1, and a twofold decrease in plasma clearance. Neither gestational and postnatal age nor birth weight correlated with the pharmacokinetic variables. No significant change in reserve bilirubin-binding capacity after an intravenous dose of furosemide was noted. Slow elimination of furosemide may partly explain the prolonged diuretic and saluretic effect of furosemide in the neonate.

Bilirubin↗
PubMed1978

Assessment of ether anesthesia in normal and spinal cats using gas--liquid chromatographic analysis of blood.

A new gas-liquid chromatographic method was developed for the determination of diethylether in whole blood. Ether was quantitated by peak area ratio analysis with n-propanol as the internal standard using a flame ionization detector. Blood ether concentrations were determined in cats undergoing inhalational anesthesia by ether in oxygen. In normal spontaneously breathing cats, anesthesia began at ether concentrations of about 0.6 g/l, and respiratory arrest occurred at 2.4 g/l and above. Mean arterial blood pressure was well maintained throughout the entire anesthetic range. In spinal artificially respired animals, mean arterial blood pressure correlated inversely with blood ether concentration. The data suggest that decline in blood pressure may be a useful sign of ether toxicity in spinal cats.

Anesthesia↗
PubMed1977

Theophylline disposition in patients with hepatic cirrhosis.

To determine the role of liver dysfunction in theophylline toxicity, we administered single intravenous doses of the drug to nine patients with cirrhosis and observed its disposition over a period of 24 to 48 hours. As compared to 19 normal subjects, these patients had a prolonged plasma half-life (mean, 25.6 vs. 6.7 hours) and a decreased plasma clearance (mean, 0.042 vs. 0.062 liter[kg-1]hr-1). Volumes of distribution of theophylline in the cirrhotic patients (central-compartment volume of 0.330, and steady-state volume of distribution of 0.785 liter per kilogram) did not substantially differ from normal (0.246 and 0.508 respectively). Plasma theophylline binding in three patients with cirrhosis averaged 36.8 per cent as compared to 52.6 per cent in four normal subjects. There was no correlation between any laboratory test of liver function and the plasma theophylline half-life, except for serum albumin (r = 0.92, P less than 0.001). The variable capacity to eliminate theophylline precludes the use of usual maintenance dose schedules for bronchodilation in cirrhosis.

Adult↗
PubMed1977

Theophylline kinetics in acute pulmonary edema.

Nine patients with acute cardiogenic pulmonary edema were given theophylline intravenously, and its disposition was observed over the next 24 hr. Compared to that in 19 normal subjects, these patients had prolonged plasma half-lifes (mean, 22.9 from 6.7 hr) and decreased plasma clearances of theophylline (mean, 0.041 from 0.062 L [kg-1] hr-1). The intersubject variation in these parameters was 20-fold in patients with pulmonary edema and 4-fold in normal subjects. Since the peak plasma concentrations attained and the apparent volumes of distribution were not different in the two groups, a suitable initial dose can be calculated. A loading dose of 4.5 to 5 mg/kg theophylline (6 mg/kg aminophylline) given over 20 min appears safe. Because of the great variability in the plasma clearance of this drug in patients with heart failure, plasma concentrations and toxicity would be unpredictable after repeated doses or constant infusions.

Acute Disease↗
PubMed1977

Effect of phenobarbital on the disposition of intravenous theophylline.

The disposition of intravenous doses of theophylline was determined in normal male subjects before and after treatment with phenobarbital 2 wk. Although there was some variation in disposition of the 2 drugs, there were no significant effects of phenobarbital on theophylline kinetics. We conclude that theophylline dosage need not be altered during concomitant administration of phenobarbital.

Adult↗
PubMed1977

Disposition of 5-fluorouracil after intravenous bolus doses of a commercial formulation to cancer patients.

A high-pressure liquid chromatographic method that is used to determine the pharmacokinetic disposition of 5-fluorouracil from the plasma compartment is presented. The method requires only 0.5 ml of plasma for each determination and is sensitive to 0.1 mg of drug per liter. Novel methodology with the use of an ion-specific electrode technique for the determination of urinary excretion kinetics of 5-fluorouracil and its metabolites is also presented. This study demonstrated a much greater variability for the disposition of 5-fluorouracil by cancer patients than has been reported previously. The apparent volume of distribution for this drug varied more than 37-fold. Its plasma half-life varied more than 19-fold, and its urinary excretion half-life varied almost 400-fold. These data are compatible with the hypothesis that this variation could account, at least in part, for the variable therapeutic and toxic response to 5-fluorouracil. The methodology presented in this study is sufficiently simple and sensitive to allow assessment of this hypothesis by investigating cancer patients who receive therapeutic doses of 5-fluorouracil.

Aged↗
PubMed1976

Pharmacokinetic aspects of theophylline in premature newborns.

To characterize further the pharmacokinetics of theophylline in premature infants, its concentraion in blood was measured by high-pressure liquid chromatography after intravenous infusion given to six apneic premature newborns three to 15 days of age. Theophylline's apparent volume of distribution was 0.690 +/- 0.095 liters per kilogram (mean +/- S.E.), a value similar to that of children, but the half-life (30.2 +/- 6.5 hours) was nine times longer. Blood clearance rate (17.6 +/- 2.3 ml per kilogram per hour) was lower than plasma clearance rate (100 ml per kilogram per hour) of young children. At a total plasma concentration of 17 mg per liter, 56.4 +/- 3.8 and 36.4 +/- 3.8 per cent of the theophylline was bound to adult or full-term cord plasma proteins, respectively. Bilirubin and theophylline did not compete for plasma protein. Calculations suggest that a loading doses of 5.5 mg per kilogram and a maintenance dose rate of 1.1 mg per kilogram per eight hours would achieve and maintain a mean blood concentration of 8 mg per liter (about 10 mg per liter in plasma).

Adult↗
PubMed1976

Pharmacokinetic analysis of the disposition of intravenous theophylline in young children.

The disposition of a single intravenous dose of theophylline, 3.2 mg/kg, was studied using a high-pressure liquid chromatographic assay in ten asthmatic children one to four years of age. The man plasma theophylline clearance was 0.100 +/- 0.036 l/kg/hr, kel 0.49 +/- 0.30 hr-1, betat1/2 3.38 +/- 1.11 hr, alphat1/2 0.13 +/- 0.09 hr, and V1 0.25 +/- 0.13 1/kg. Plasma theophylline clearance was approximately 40% greater in these children than that reported in adults, mainly due to an increased rate of drug elimination. Large interindividual differences were observed. Analysis of data using either a two- or one-compartment model yielded almost identical dosage regimens designed to rapidly achieve and maintain a chosen plasma theophylline concentration. Calculations based upon mean values of pharmacokinetic constants predict that a maintenance dose rate for aminophylline of 30 mg/kg/day, after a loading dose of 5.6 mg/kg, would rapidly achieve and maintain a mean steady-state plasma concentration of theophylline of 10 mg/1. Potential toxicity of such a regimen has not been excluded, since therapeutic trials (with achievement of steady state) have not yet been conducted.

Child, Preschool↗
PubMed1976

Modified colorimetric method for procainamide in plasma.

We describe a modified colorimetric method for determining procainamide in plasma by use of a diazotization and coupling reaction with N-(1-naphthyl)-ethylenediamine dihydrochloride (Marshall's reagent). The sensitivity of the assay is increased twofold over the originally reported colorimetric method, and the lower limit of detection for the assay of a 1.0-ml plasma sample has been decreased to 0.5 mg/liter.

Colorimetry↗