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Biomedical subjects

D H Huffman

Publications and source records attributed to D H Huffman.

At least 19 recordsLinked to original sources
PubMed1978

Quantitation of lidocaine and its deethylated metabolites in plasma and urine by gas chromatography-mass fragmentography.

A sensitive, precise and accurate method for simultaneous quantitation of lidocaine and its deethylated metabolites by gas chromatography-mass fragmentography has been developed. Propyl derivatives of the deethylated metabolites are formed directly in either plasma or urine by treatment with propionaldehyde and sodium cyanoborohydride. The propyl derivatives and unchanged lidocaine are extracted, separated by gas chromatography and quantitated by mass fragmentography using mepivacaine as the internal standard. Quantitation of these compounds to levels as low as 50 ng/ml body fluid has been achieved with coefficients of variation less than 10%.

Chromatography, Gas↗
PubMed1978

Impairment of antipyrine clearance in humans by propranolol.

The effect of propranolol on antipyrine clearance in humans was evaluated in six healthy volunteers who received single 1.4 to 1.5 g doses of intravenous antipyrine on two occasions. The first (control) antipyrine trial was without concurrent drug administration; the second trial was done during treatment with therapeutic doses of propranolol (40 mg every 4 to 6 hours). Antipyrine elimination half-life (t1/2), volume of distribution (Vd), and total clearance were determined after each trial. In all subjects isoproterenol sensitivity decreased markedly during propranolol treatment, indicating a high degree of beta blockade produced by the drug. Mean antipyrine t1/2 during the propranolol treatment period was significantly prolonged, and total clearance significantly reduced, over the control values. Twenty-four-hour urinary excretion of 4-hydroxyantipyrine, the major metabolite of antipyrine, likewise was reduced from 23.6% of the dose on the control trial to 14.8% of the dose during propranolol coadministration (0.1 less than P less than 0.2). Vd however, was nearly identical during both trials (0.62 L/kg). Thus propranolol prolongs the half-life and reduces the clearance or biotransformation rate of antipyrine, a drug whose clearance is independent of hepatic blood flow. Propranolol may influence the activity of hepatic microsomal enzymes responsible for drug hydroxylation.

Adult↗
PubMed1977

Digoxin in hyperthyroidism.

A patient with chronic atrial fibrillation developed hyperthyroidism. Increasing doses of digoxin were required to maintain satisfactor ventricular rate control. The systemic availability of oral digoxin was decreased in this patient. The metabolism of digoxin was studied in the hyperthyroid rats. The plasma digoxin concentrations were significantly decreased in the hyperthyroid rats. A threefold increase in digoxin excretion in the bile of the hyperthyroid rats was associated with these changes in plasma digoxin concentrations. Conversely, hypothyroid rats excreted less digoxin in the bile when compared with control and hyperthyroid rats. Thus, changes in digoxin absorption and its biliary excretion result, in part, in a decreased therapeutic effect of digoxin based on dose in hyperthyroidism.

Animals↗
PubMed1977

Bioavailability of digoxin-hydroquinone complex: a new oral digoxin formulation.

A new oral digoxin formulation, a digoxin-hydroquinone complex (99% dissolution at 5 min), was evaluated in 12 healthy human volunteers with reference to bioavailability and extent and time of peak serum digoxin levels. This preparation was compared with a commercial digoxin tablet (26% dissolution at 5 min), digoxin elixir, and a parenteral digoxin solution. Bioavailability was assessed by the 24-hr area under the serum digoxin-time curve and 48-hr digoxin excretion in urine. The bioavailability of the complex was similar to that of the elixir but not statistically different from that of the tablet. The tablet was less bioavailable than the elixir. There was less interindividual variation in bioavailability with the complex than with the elixir. Peak serum digoxin levels were higher with the complex than the tablet and were achieved more quickly.

Administration, Oral↗
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

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

Serum quinidine concentrations: comparison of fluorescence, gas-chromatographic, and gas-chromatographic/mass-spectrometric methods.

Serum quinidine concentrations were determined in patients on chronic therapeutic doses. Although results were higher by a protein precipitate-fluorescence method as compared to a specific extraction fluorescence method, there was substantial correlation between results by the two methods (r = 0.945, P less than 0.001). We established the specificity of the extraction method by a methylation gas-chromatographic method in which the base peak in the mass spectra of the methylated products of both quinidine and cinchonidine, the internal standard, was monitored. We conclude that the protein precipitate method should be discarded.

Arrhythmias, Cardiac↗
PubMed1976

Clinical use of digitalis glycosides.

The pharmacology of digitalis compounds is reviewed, and the clinical use of the cardiac glycosides is discussed with particular attention to the selection of patients for digitalis therapy and to a study of the usefulness of various methods to monitor digitalis therapy. The discussion includes pharmacokinetics, clinical considerations, and digitalis toxicity and its treatment. It is concluded that the digitalis glycosides remain the most useful and reliable drugs for producing a long-term increase in myocardial contractility. However, in view of the high frequency of toxicity, it is important to consider the possibility that these drugs may have been overused.

Digitalis Glycosides↗
PubMed1975

Relationship between digoxin concentrations in serum and saliva.

The concentration of digoxin in serum and saliva was determined in 18 patients receiving digoxin. Unlike serum, it was necessary to extract saliva with chloroform in order to quantitate digoxin levels accurately. An excellent linear correlation (r = +0.988, p less than 0.001) was observed between the saliva and serum digoxin concentrations. This indicates that saliva digoxin concentrations can be used to monitor digoxin therapy, particularly in patients in whom blood sampling is inconvenient or difficult. The saliva/serum ratio for digoxin concentration was 0.78 plus or minus 0.07 (SD). Since the digoxin binding to plasma proteins is 23%, it is the free drug that is in equilibrium between serum and saliva.

Digoxin↗
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↗