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Biomedical subjects

D S Sitar

Publications and source records attributed to D S Sitar.

At least 109 records · Page 6Linked to original sources
PubMed1985

Amantadine kinetics in healthy elderly men: implications for influenza prevention.

Amantadine kinetics were investigated in 10 healthy elderly men 60 to 76 yr old. We calculated a dose that would yield the same trough steady-state plasma amantadine concentration (Cpss; 300 ng/ml) as a 200 mg/day dose taken by young healthy adults; this dose prevents influenza A virus infection and is well tolerated by this population. With a one-compartment open model, kinetic parameters were calculated after a single dose of 25, 50, or 75 mg or the same dose twice a day for 10.5 days. Peak concentration occurred 4.0 to 8.0 hr after dosing, but the calculated AUC was proportional to dose, indicating that relative bioavailability was independent of dose. This was supported by recovery of 88% of the single doses in urine. No change in apparent volume of distribution was found. Log trough Cpss increased with dose. Trough Cpss varied less than 300% for equivalent doses. There was first-order elimination of drug from plasma, with a median t1/2 of 28.9 hr (range 18.5 to 45.0 hr), and elimination was independent of dose and creatinine clearance. The median ratio of renal amantadine clearance to creatinine clearance was 2.07 (range 0.64 to 4.20), suggesting renal tubular secretion. Compared to data from healthy young adults, the t1/2 was doubled and renal drug clearance was diminished in elderly men. To achieve the target trough Cpss of 300 ng/ml, healthy older men must take amantadine at a dose of 1.4 mg/kg/day, and we suggest that this is a rational dose for evaluation of efficacy and safety for influenza A prophylaxis in this population.

Age Factors↗
PubMed1985

Ethanol disposition in newborn lambs and comparison of alcohol dehydrogenase activity in placenta and maternal sheep, fetal and neonatal lamb liver.

The kinetic disposition of ethanol was studied in neonatal lambs. The mean plasma clearance rate was 36 mg/l/h, 17% of that in near-term pregnant sheep. Activity increased slowly during the first 5 days of life. Hepatic alcohol dehydrogenase activity in the neonatal lamb was only 7% of that in adult sheep, but was similar to activity in the near-term fetus. Placental enzyme activity was even lower than that in the fetus and neonate, suggesting only a minor role for it in the metabolic disposition of ethanol during pregnancy. The pH optimum for alcohol dehydrogenase was higher in the fetus and neonate (9.6) than in maternal liver or placenta (9.0). The pharmacodynamic consequences of prolonged neonatal exposure to ethanol due to impaired metabolism remain to be explored.

Aging↗
PubMed1985

Ethanol disposition in man: comparison of breathalyzer and two methods of gas-liquid chromatography.

Blood and plasma ethanol concentrations were determined in 12 healthy male volunteers by gas-liquid chromatography (GLC) using direct injection (DI), headspace injection (HSI), and Breathalyzer (BR) analyses. Plasma concentrations as well as the blood:breath partition ratio of ethanol were higher by GLC-DI than by GLC-HSI. Regardless of analytical method used, the concentrations of ethanol in blood and rate of ethanol clearance from blood or plasma were unchanged. The partition ratio upon which the BR data are based appears adequate for individuals with normal pulmonary function.

Breath Tests↗
PubMed1985

Sulfasalazine in severe rheumatoid arthritis: a study to assess potential correlates of efficacy and toxicity.

Thirty-one patients with chronic active rheumatoid arthritis (RA) resistant to gold and/or penicillamine therapy, were treated with sulfasalazine, 2-3 g daily, in a 12-week open study. Nineteen patients completed the study, and of these, 13 showed clinical improvement. Twelve patients were withdrawn from the study because of nausea (8), mouth ulcers (1), disease flare (1) and noncompliance (2). There was no significant difference in serum sulfasalazine concentrations among responders, nonresponders and patients who were withdrawn. Our data suggest that sulfasalazine may be of benefit in the treatment of RA. Further studies are necessary to determine if toxicity and/or efficacy might be related to serum concentrations of sulfasalazine metabolites.

Adult↗
PubMed1985

Plasma and synovial fluid concentrations of salicylic acid and its metabolites in patients with joint effusions.

Equilibration of salicylic, salicyluric and gentisic acids between plasma and synovial fluid (SF) was measured in 36 patients receiving chronic salicylate therapy and from whom SF was required for diagnostic purposes. Gentisic and salicyluric acids equilibrated completely, while SF salicylic acid concentration was less than that in plasma. The presence of significant gentisic acid concentrations in SF could contribute to the therapeutic response to chronic salicylate therapy, since its antiinflammatory effect is even greater than that of acetylsalicylic acid.

Adult↗
PubMed1984

Foetal responses to acute haemorrhage under halothane anaesthesia.

The effect of halothane anaesthesia on the foetal responses to acute haemorrhage was studied in chronically prepared ewes. An average of 27.9 ml X kg-1 of foetal blood was withdrawn resulting in an acute 20 per cent decrease in mean arterial pressure which returned toward the control value after 186 seconds. After the blood loss, cardiac output was reduced by 26.1 per cent and heart rate decreased by 26 per cent. Blood flows to the kidneys, placenta and musculoskeletal structures were reduced by 24.7, 38.2 and 35.3 per cent respectively but flow to the brain increased by 30 per cent. Reinfusion of lost blood, corrected flow reductions and the supply to the gastrointestinal organs increased above control values. This study showed that foetal lambs were able to tolerate an acute blood loss under halothane anaesthesia. An adequate perfusion pressure and blood flow to critical organs, such as the brain was maintained by increasing systemic vascular resistance. The compensation, however, was incomplete. Placental blood flow, maternal-foetal gas exchanges, and redistribution of cardiac output away from gastrointestinal tract and skin were impaired.

Anesthesia, Obstetrical↗
PubMed1984

Maternal and fetal ethanol pharmacokinetics and cardiovascular responses in near-term pregnant sheep.

The disposition and cardiovascular effects of ethanol were studied in near-term pregnant sheep and their fetuses after intravenous infusions either to the mother or the fetus. Placental transfer of ethanol from mother to fetus was rapid, but transfer from the fetal to maternal circulation was impaired when ethanol was administered directly to the fetus. Plasma clearance of ethanol was similar from the mother and fetus in utero. In the maternal infusion experiments, both maternal and fetal heart rate increased with plasma ethanol concentration. However, in the fetal infusion experiments, both maternal and fetal heart rate increased with plasma ethanol concentration. However, in the fetal infusion experiments, fetal heart rate was inversely related to plasma ethanol concentrations while maternal mean arterial blood pressure increased with maternal plasma ethanol concentration. Further studies in neonatal lambs are needed to determine if ethanol has adverse effects on hemodynamics when the neonate is separated from its protective intrauterine environment.

Animals↗
PubMed1983

Aging and heavy drug use: a prescription survey in Manitoba.

A random sample of claimants under Manitoba's Pharmacare plan provided information on the drugs prescribed for those individuals who spent more than $50 for drugs in 1978. More women than men were represented among the 412 claimants aged 50 to 64 (58% females), and more drugs were prescribed for women than men (8.38 +/- 3.4 vs. 7.17 +/- .33, mean +/- S.E.M., p less than 0.02). For the 403 claimants aged 65 and older, the sex distribution matched that of the general population (55%), and the difference in number of drugs prescribed was not statistically significant (8.49 +/- .36 vs 7.98 +/- .35). For the claimants aged 65 and older, the five most heavily prescribed drug categories were thiazide-type diuretics (prescribed for 51.6% of older claimants in 1978), benzodiazepines (40.0%), salicylates (26.8%), digoxin (22.6%) and codeine (20.8%). There were few differences in prescription frequencies between younger and older claimants, and these data indicate that drugs prescribed for heavy drug users do not change markedly as a function of age.

Aged↗
PubMed1983

Age-related morphine kinetics.

The kinetic disposition of morphine was compared in 13 young and 7 older healthy subjects after a single intravenous dose of 10 mg/70 kg morphine. The apparent volume of distribution at steady state in elderly subjects was only half of that in young subjects. This difference was derived from reductions in both central and peripheral kinetic compartment volumes in the older subjects. The beta elimination phase for morphine was more rapid, but its plasma clearance was reduced in older subjects. Calculation of the peripheral compartment morphine concentration for these subjects indicated that drug concentration in this kinetic space was higher in older subjects for 1.5 hr after dosing.

Adult↗
PubMed1983

Effect of aging on response to induction and metabolizing activity of the hepatic mixed-function oxidase system of male Sprague-Dawley rats.

The composition and activity of the rat hepatic mixed-function oxidase system were investigated, in male rats 17 to 127 weeks old, with respect to content of its various components and their response to induction by phenobarbital and beta-naphthoflavone. There were decreases in many of the components of this enzyme system in older rats which could not be fully compensated by phenobarbital induction. However, there appeared to be no age-related loss of response to induction by beta-naphthoflavone. Decreases in mixed-function oxidase enzymes with age did not occur at the same rate or to the same extent. Metabolic studies with ethylmorphine and aniline demonstrated some age-associated changes which did not necessarily parallel reductions in the enzyme system. For example, there was a reduction in apparent Km as a function of age for the hydroxylation of aniline in rats treated with beta-naphthoflavone, even though they showed no apparent change in the amount of cytochrome P-450. There was also a trend to altered Km for the demethylation of ethylmorphine in saline or corn oil treated rats in older animals. We feel that these changes are a reflection of differential reductions in the various isoenzymes of cytochromes P-450. Further studies are planned to confirm this hypothesis.

Aging↗
PubMed1983

Fetal anesthetic requirement (MAC) for halothane.

We asked whether the anesthetic requirement (MAC) of fetal lambs is lower than that of pregnant ewes. In five pregnant ewes anesthetized with a subarachnoid block, a fetal foot was withdrawn through a hysterotomy. The ewe then breathed 1.5% halothane and a clamp was applied to the fetal foot at 2-min intervals. We concomitantly obtained arterial blood from previously implanted catheters. When fetal movement in response to clamping the foot ceased, halothane was discontinued and the stimulus and sampling continued until the fetus began to move. Anesthesia was again resumed and continued until movement stopped. Anesthesia was then deepened and MAC was determined in the mother (stimulus--ear clamp). The fetal blood concentrations of halothane at MAC were 48 +/- 28 mg/L; they were 133 +/- 5 mg/L in the mother. This difference was highly significant (P less than 0.001). Calculated end-tidal concentrations were 0.33% and 0.69%, respectively. In two animals delivered by cesarean section, MAC increased progressively over the first 12 h of life. Progesterone levels concomitantly decreased.

Animals↗
PubMed1982

Effect of ethanol ingestion on outcome of drug overdose.

It was traditionally assumed that ethanol, as part of an intentional drug overdose, will increase morbidity and mortality. The authors prospectively studied the effect of ethanol on the outcome of intentional drug overdose in 468 adults, 196 of whom required hospital admission. Ethanol was detected in significantly fewer patients who required admission. Ethanol ingestion was not related to coma, impaired vital signs or mortality. Indeed, the duration of coma was significantly shorter in patients in whom ethanol was detected, but this group had a lesser incidence of multiple drug and nonbarbiturate hypnotic ingestion and a greater incidence of chronic ethanol use. Thus, it seems that ethanol is not associated with a worse clinical course if the drug overdose patient reaches medical care before an irreversible event.

Adolescent↗
PubMed1982

Propylthiouracil disposition in pregnant and post-partum women.

Propylthiouracil (PTU) disposition was investigated in hyperthyroid women during pregnancy and post partum. The plasma half-life after the first dose averaged 0.66 h and became greater than 1 h with chronic drug therapy. The apparent volume of distribution after the first dose averaged 0.26 liter/kg, similar to nonpregnant hyperthyroid patients. There was a tendency to increased apparent volume of distribution with chronic drug ingestion. Plasma clearance of PTU showed no change related to disease or to pregnancy. Our data suggest that pregnancy does not have a major effect on the pharmacokinetic disposition of PTU in the hyperthyroid mother. Observation of a prolonged plasma half-life for PTU in 1 patient post partum deserves further investigation to determine if this change is associated with clinically significant therapeutic or toxic effects.

Adult↗
PubMed1981

Ethanol 'dose-dependent' elimination: Michaelis-Menten v classical kinetic analysis.

1 To compare classical linear regression techniques and a Michaelis-Menten elimination model eight normal human volunteers each received three intravenous doses (0.375, 0.5, and 0.75 g/kg) of ethanol and four of the subjects each received four oral doses (0.5, 0.65, 0.95, 1.25 g/kg) of ethanol. 2 Computerized analysis of the time-plasma concentration profiles using a two-compartment Michaelis-Menton elimination model yielded a median absorption constant of 1.29 h-1; volume of distribution of 0.47 l/kg; Vmax of 0.12 g h-1 kg-1; and Km of 0.03 g/l. Classical techniques resulted in a slope of 0.20 g l-1 h-1, volume of distribution of 0.55 l/kg, and a B60 of 0.11 g h-1 kg-1. 3 Transient post-prandial decreases in elimination slope occurred at higher oral doses. A trend of increasing slope with increasing oral dose was seen at concentrations well above the Km. Time to sobriety (0.8 g/l) increased nonlinearly with increasing peak concentration. 4 Maximal ethanol elimination rates are determined equally well by the two techniques. Classical analyses overestimate the volume of distribution of ethanol by 17%. Neither technique helps explain the post-prandial changes in slope or increasing slope with dose at high concentrations.

Adult↗
PubMed1981

Increased serum salicylate metabolites with age in patients receiving chronic acetylsalicylic acid therapy.

A high pressure liquid chromatographic method was used to measure the serum concentrations of salicylic, salicyluric and gentisic acids in patients receiving chronic acetylsalicylic acid therapy. There was good correlation between this method and the established colorimetric assay for salicylic acid. The concentration of gentisic and salicyluric acids were increased in patients older than 60 years. No correlation was found with sex, concomitant ingestion of other drugs, serum creatinine or serum albumin.

Adult↗
PubMed1980

Kinetic disposition and diuretic effect of frusemide in acute pulmonary oedema.

The kinetic disposition and diuretic effect of frusemide was assessed in 16 patients with acute pulmonary oedema utilizing a specific gas-liquid chromatographic assay for the drug. Serum frusemide concentrations decayed biexponentially with wide variation in both alpha half-life (range 15-79 min) and beta half-life (range 127-1190 min). The beta phase half-life was inversely related to creatine clearance. The apparent volume of distribution varied greatly among the patients (range 0.085-0.818 l/kg), and patients with an acute myocardial infarction had a larger peripheral kinetic compartment. Patients with acute myocardial infarction excreted less unchanged drug and had a lesser urinary excretion of sodium and volume compared to patients without infarction. The urinary excretion of sodium, chloride, calcium and volume was linearly related to the urinary excretion of unchanged frusemide.

Adult↗