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Biomedical subjects

D L Azarnoff

Publications and source records attributed to D L Azarnoff.

At least 55 records · Page 3Linked to original sources
PubMed1977

Metabolic disposition of antipyrine in patients with lung cancer.

The metabolism of antipyrine (10 mg/kg i.v.) was studied in nine patients with cancer of the lung and in a cancer-free control group matched for age, sex, drug intake, and smoking and drinking history. The mean plasma clearance of antipyrine was 0.0475 +/- 0.009 liter/kg/hr in the tumor group and 0.0557 +/- 0.007 liter/kg/hr in the control group (p greater than 0.05). The antipyrine plasma elimination half-life was longer in the group with tumors (9.5 +/- 1.3 hr) compared to the control group (7.7 +/- 1.3 hr), but the difference was not statistically significant (p greater than 0.05). There was no difference between the groups in the excretion of two major antipyrine metabolites, 4-hydroxyantipyrine and N-demethylantipyrine, in a 48-hr urine sample. Thus, the presence of lung cancer in humans does not significantly alter antipyrine elimination.

Adult↗
PubMed1976

Phenytoin: pharmacokinetics and bioavailability.

The pharmacokinetics of a single 300-mg oral and intravenous and 14 daily 300-mg oral doses of phenytoin were studied in 6 healthy volunteers. The mean plasma elimination t1/2 was the same following intravenous (16.8 +/- 1.3 hr) and oral (17.1 +/- 1.5 hr) doses of phenytoin; however, following chronic oral administration, the t1/2 increased to 18.9 +/- 1.5 hr (p less than 0.05). The absolute bioavailability of an oral dosage form (Dilantin Kapseals) varied from 57.7 to 85.6% when based on the relationship between the corresponding single dose areas under the curve (AUCs). When based on the comparison of the AUC for multiple oral dosing with the single iv dose area, average bioavailability was 85.9% (71.8 to 106.3). Since the variation in the bioavailability and elimination of phenytoin does not allow accurate prediction of the steady-state plasma concentration, monitoring plasma levels may be of special importance.

Administration, Oral↗
PubMed1976

One-year trials with halofenate, clofibrate, and placebo.

The hypolipidemic as well as other laboratory and clinical effects of halofenate, clofibrate, and placebo were compared in 29 patients with type IV hyperlipoproteinemia in a double-blind, controlled, therapeutic trial of 1 yr duration. Plasma drug levels were obtained to monitor compliance. Clofibrate and halofenate lowered serum triglycerides to a similar extent. The hypotriglyceridemic effect of halofenate was significant only when data from noncompliant patients were discarded. Only clofibrate lowered baseline levels of plasma cholesterol. Very low density lipoproteins were decreased and low density lipoproteins were increased by clofibrate but not by halofenate. Halofenate had a marked hypouricemic effect that was greater than that of clofibrate. The hypouricemic effect of halofenate and clofibrate was paralleled by a concomitant decrease in serum bilirubin. Abnormal increases in serum creatine phosphokinase were observed with both drugs primarily in patients who had abnormal initial levels.

Adult↗
PubMed1976

The interaction between halofenate and propranolol.

The effect of halofenate on beta adrenergic blockade by propranolol was studied in 4 subjects during chronic drug administration in a randomized, double-blind study. The plasma propranolol concentration was significantly lower during treatment with halofenate than with placebo. The reduction in propranolol levels correlated with a decrease in beta adrenergic blockade. The mechanism for the decrease in plasma concentration has not been determined.

Adult↗
PubMed1976

In vitro inhibition of rat liver cholest-5en-3 beta-ol (cholesterol) biosynthesis by non-mercurial sulfhydryl reagents.

In vitro conversion of 2-14C-mevalonate to cholest-5en-3 beta-ol (cholesterol) in rat liver homogenates is inhibited by arsenite, beta-mercaptoethanol, dithiothreitol and ethanethiol. Two sterols containing 20 carbon atoms accumulate under these conditions. One of these is identified as 4,4 dimethyl-5alpha-cholest-8en-3beta-ol and the other tentatively identified as 4,4 dimethyl-5alpha-cholest-8,24-dien-3beta-ol. Based on these observations, these non-mercurial sulfhydryl reagents do not inhibit 5alpha-lanosta-8,24-dien-3beta-ol 14alpha demethylase.

Animals↗
PubMed1976

Drug protein binding and the nephrotic syndrome.

A reduction in plasma albumin concentration, as seen in patients with the nephrotic syndrome, is usually associated with a decrease in plasma protein binding of highly bound drugs. Therefore, the fraction of the unbound drug increases, but the absolute free concentration remains essentially unchanged due to a compensatory reduction in the steady state total plasma concentration. With phenytoin, protein binding and plasma albumin concentration are closely related, so that the degree of binding can be estimated without specific binding techniques. To be able to correctly interprete plasma levels the degree of protein binding should be known, since a reduced total concentration may be fully effective, if the free drug fraction is increased in hypoalbuminaemic patients. Although the mean steady state plasma concentration of highly bound drugs is not affected in the nephrotic syndrome, a greater fluctuation of the unbound level is observed between doses, offering a possible explanation for the increased incidence of toxicity in hypoalbuminaemic patients. As a consequence, shorter dosing intervals of these drugs seems to be advisable, rather than a reduction in the total daily dose. Reduced protein binding is accompanied by an increase in the total plasma clearance which is a function of the elimination rate constant and the volume of distribution.

Antipyrine↗
PubMed1975

Diphenylhydantoin: correlation between protein binding and albumin concentration.

The unbound fraction of diphenylhydantoin is inversely correlated with the patient's serum albumin concentration and can be accurately estimated graphically without binding analyses. The data for this relationship was obtained from a study in which we observed that the unbound fraction of diphenylhydantoin was two times higher in patients with the nephrotic syndrome. However, in these patients it was not necessary to diminish the dosage since the absolute concentration of unbond drug was unchanged due to a compensatory increase in the apparent volume of distribution and plasma clearance.

Half-Life↗
PubMed1975

Intersubject variation in absorption of digoxin in normal volunteers.

The absorption of oral digoxin preparations was evaluated following single-dose administration of 0.5 mg of digoxin to 16 normal volunteers in a randomized crossover design. Absorption was estimated using the cumulative excretion of digoxin in urine for 7 days and the area under the 24-hr serum digoxin concentration curve (AUC). Significant intersubject variability was observed with both parameters, but this variability was greater for the AUC. After intravenous administration, the 7-day digoxin excretion was 68% of the dose. The elixir and a rapid dissolution tablet were significantly better absorbed (84.5 and 77.8%, respectively) than was a slow dissolution tablet (66.7%), as reflected by the fraction of the amount excreted in the urine following intravenous administration of the same dose. There was a highly significant correlation between the cumulative digoxin excretion in urine during the first 2 days compared to 7 days (r = +0.972,p less than 0.001). Bioavailability of oral digoxin preparations can be reliably determined by comparison of the cumulative 2-day excretion of digoxin following a single dose.

Administration, Oral↗
PubMed1975

Pharmacokinetics of drugs in patients with the nephrotic syndrome.

Since the binding of drugs to plasma proteins can significantly after the intensity of pharmacological and toxicological effects of drugs, we studied the pharmacokinetics of three drugs in patients with hypoalbuminemia secondary to the nephrotic syndrome, but with relatively normal renal function. No significant differences were seen in the pharmacokinetic parameters observed for antipyrine, a drug which is less than 10% bound to plasms proteins. The percentage of unbound diphenylhydantoin, a highly plasms protein-bound drug, was found in patients with the nephrotic syndrome to be twice that of healthy individuals (19,2 vs. 10.1%, P smaller than 0.001). However, there was also a lower steady-state plasma concentration of diphenylhydantoin (2.9 plus or minus 0.6 vs. 6.8 plus or minus 0.6 mug/ml, P smaller than 0.001) secondary to an increase in the plasms clearance (0.048 plus or minus 0.019 vs. 0.022 plus or minus 0.006 liter/kg.h, P smaller than 0.001) in the nephrotic patients. The net effect is no difference in the absolute concentration of unbound diphenylhydantoin in healthy individuals (0.69 plus or minus 0.05 mug/ml) and patients with the nephrotic syndrome (0.59 plus or minus 0.06 mug/ml). Qualitatively, similar differences were observed with clofibrate. The dose of these drugs need not be routinely reduced in patients with the nephrotic syndrome as long as they have reasonably normal renal function (creatinine clearance greater than 50 ml/min). With all highly bound acidic drugs, knowledge of the concentration of unbound drug is essential to the proper interpretation of total blood levels and subsequent treatment of the patient.

Adult↗
PubMed1975

Placental transfer and fetal urinary excretion of gentamicin during constant rate maternal infusion.

Placental transfer and fetal urinary excretion of gentamicin was studied in midtrimester goat and human previable fetuses during constant rate maternal infusion with the drug. Gentamicin was not detected in the serum of any of the goat fetuses, even when maternal serum concentrations ranged from 15.2 mug/ml to 20.9 mug/ml. However, gentamicin was present in the amniotic fluid of four animals. Gentamicin was also present in fetal urine collected from three animals. In contrast human fetal central venous serum concentrations of gentamicin were 21-37% of those in maternal serum after constant rate infusion of the mother. In addition, gentamicin was present in human fetal urine in concentrations 2-- 3 times those in fetal serum. The observed difference in fetal serum concentration of gentamicin between the two species represents a difference in placental permeability to gentamicin and/ or a difference in fetal renal clearance of the drug.

Amniotic Fluid↗