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Biomedical subjects

H Halkin

Publications and source records attributed to H Halkin.

At least 91 records · Page 5Linked to original sources
PubMed1980

Digoxin-quinidine interaction: in vitro studies in rat tissue.

Clinically, the administration of quinidine to digitalized patients results in an elevation of serum digoxin concentration. It has been suggested that quinidine displaces tissue-bound digoxin and that renal digoxin clearance is reduced. We studied the influence of digoxin-quinidine interaction on 125I-digoxin uptake by various rat tissues in vitro, employing the tissue slice method. S/M digoxin ratios were kidney 1.72 +/- 0.24 (mean +/- S.D.), heart 2.36 +/- 0.31, muscle 2.05 +/- 0.21 (n = 23 for each), and fat 0.25 +/- 0.10 (n = 9). Addition of quinidine to the incubation medium resulted in a 17.4% reduction of digoxin uptake by kidney tissue to 1.42 +/- 0.38 (n = 24) (p < 0.01). Quinidine failed to reduce digoxin uptake in both heart and striated muscle. Metabolic blockade resulted in a significant reduction in digoxin uptake in kidney slices from 1.93 +/- 0.23 to 1.34 +/- 0.18 with DNP (n = 10) and to 1.30 +/- 0.15 (n = 10) with sodium azide (p < 0.001). Digoxin uptake in either heart or muscle was uninfluenced by metabolic blockers. We conclude that active energy-dependent transport mechanism for digoxin exists in renal cortical tissue. This mechanism is inhibited by either quinidine or metabolic blockers. In contrast, uptake in heart or muscle represents a different transport mechanism unaffected by quinidine or metabolic blockers.

Animals↗
PubMed1980

Inadequacy of reported intake in assessing the potential hepatotoxicity of acetaminophen overdose.

No evidence of liver damage was found in a series of 22 patients with acute acetaminophen overdose, 13 of whom reported ingesting doses of 10 to 25 g, which is within the accepted hepatotoxic range. Serum acetaminophen concentrations did not exceed 160 micrograms/ml, an amount well below the minimal hepatotoxic level. Moreover, mean serum concentrations of acetaminophen in patients reporting the ingestion of less than 10 g [74 +/- 48 (SD) micrograms/ml) were similar. Throughout the study, no correlation was found between serum concentrations and the reported dose ingested. Poor bioavailability of local acetaminophen formulations was ruled out as a factor in the dose-concentration discrepancy by comparison with a British formulation ingested by four volunteers. We conclude that information regarding dose ingestion given by patients admitted to hospital for self-poisoning is inaccurate and often exaggerated. Management of acute acetaminophen overdose must be based on serum concentrations of acetaminophen and not on the reported dose.

Acetaminophen↗
PubMed1979

Serum concentrations of isosorbide dinitrate produced by a sustained-release capsule.

The bioavailability of isosorbide dinitrate (ISDN) and the time course of its serum concentration produced by a standard 20-mg tablet and a sustained-release capsule were compared in six normal volunteers. Following administration of the tablet, serum ISDN concentrations reached a peak of 29 ng/ml at 0.5 h, declined monoexponentially with a t1/2 of 25.5 min, and disappeared after 2 to 3 h. Following the administration of the sustained-release capsule, serum ISDN concentrations reached a plateau of 4 ng/ml between 2 and 5 h, and declined slowly and nonlinearly up to and including the 10-h point. The total amount of ISDN absorbed was 1.32 times greater with the standard tablet; following the absorption of the capsule, there was truncation of the serum concentration curve due to ongoing absorption at and beyond 10 h.

Administration, Oral↗
PubMed1979

Value of serum digoxin concentration measurement in the control of digoxin therapy in atrial fibrillation.

The association between steady-state serum digoxin concentrations and control of ventricular response rate (VRR) was studied in 53 consecutive patients with atrial fibrillation. Decreases in VRR were significantly correlated with serum digoxin (rs = -0.22, P less than 0.05). Clinical responses were appropriate to serum digoxin concentrations in 37 patients (69.8%) and were inappropriate in 16 (30.2%) (P less than 0.05). Complicating clinical factors were present in all eight patients with inappropriate responses to therapeutic serum digoxin (0.5 to 2.0 ng/ml) (P = 0.046), but were also found in many patients with appropriate responses and thus could not serve to differentiate between the two categories. Digitalis intoxication occurred in one of the three patients with a concentration of serum digoxin greater than 2 ng/ml (P = 0.056). In 30% of our patients with atrial fibrillation, monitoring of serum digoxin was of value in identifying inappropriate therapeutic responses indistinguishable by clinical means and in defining the subgroup of refractory cases, which allows the prevention of digitalis intoxication.

Atrial Fibrillation↗
PubMed1979

Steady-state serum quinidine concentration: role in prophylactic therapy following acute myocardial infarction.

Steady-state serum quinidine concentrations were monitored in 24 patients with acute myocardial infarction who were on a 1,300-mg daily dosing regimen. Mean serum concentrations spanned the therapeutic range, from 2 to 6 microgram/ml in 21 patients. In no patient was the level of 7 microgram/ml exceeded. Mean levels were similar in patients with congestive heart failure [3.6 +/- 1.5 (SD) microgram/ml] as in those free of failure (3.2 +/- 1.3 microgram/ml), and did not vary with impairment of renal function. There was a significant correlation between mean individual serum quinidine concentrations and the rate-normalized QT interval prolongation (r = 0.54, P less than 0.01); however, variability of the response was high. Variability of the mean serum quinidine levels among individuals was 41%. Variability within individual patients was only 18%. In the individual patient receiving prophylactic oral quinidine therapy, monitoring serum quinidine levels appears to be an accurate, reproducible and pharmacologically significant guideline to therapy.

Adult↗
PubMed1978

Steady state serum concentrations and renal clearance of digoxin in neonates, infants and children.

Steady state serum concentrations of digoxin were determined repeatedly in 34 infants with congenital heart disease. Simultaneous measurements of renal clearances of digoxin, creatinine and urea were obtained in 29 of the subjects. Serum digoxin concentrations were markedly higher in children under the age of 3 months than in those over this age, despite equal weight--adjusted 24 h doses. This finding was explained by a very rapid increase in renal digoxin clearance in the first 3 months--32 +/- 7 ml/min/1.73m2 at 1 week to 65.6 +/- 30 at 3 months. The subsequent increase in digoxin clearance was much slower, e. g. to 87.7 +/- 43 ml/min/1.73m2 at 12 months. Renal clearance of digoxin was equally well correlated with creatinine clearance (r = 0.87) as with urea clearance (r = 0.83), but it exceeded that of creatinine in all age groups. The findings indicate that both glomerular and tubular function is involved in the renal elimination of digoxin in young children, and that development of renal elimination of the drug parallels that of the maturation of renal function in the early months of life. The neonate and infant with congestive heart failure display impaired ability to eliminate digoxin. The impairment lessens rapidly with the development of renal function over the first 3 months of life. Diminished doses of digoxin should be advocated in this age group if therapeutic serum concentrations of the drug are to be maintained and toxicity avoided.

Aging↗
PubMed1978

Steady state serum digoxin concentration in relation to digitalis toxicity in neonates and infants.

Steady state serum digoxin concentrations were determined in 34 neonates and infants receiving standard maintenance doses of the drug. Digitalis intoxication, diagnosed by ECG criteria, occurred in four of 13 patients with a serum concentration above 2 ng/ml and not in any of 21 subjects with a serum digoxin concentration below this level. This association was found to be significant. It seems that the concept of increased tolerance to digoxin hitherto ascribed to infants is not tenable and that the monitoring of serum digoxin concentration is essential to treatment in this age group.

Digitalis Glycosides↗
PubMed1975

Determinants of the renal clearance of digoxin.

The renal clearances of digoxin, creatinine, and urea nitrogen were determined simultaneously in each of 41 patients receiving digoxin, in most of whom there was prerenal azotemia. Mean plus or minus SD values were: blood urea nitrogen (BUN), 26.1 plus or minus 12.8 mg per 100 ml; creatine, 1.1 + 0.41 mg per 100 ml; creatinine clearance, 78 plus or minus 42 ml/min/1.73 m2; digoxin clearance, 66.6 plus or minus 42.1 ml/min/1.73 m2; urea nitrogen clearance, 27.8 plus or minus 19.2 ml/min/1.73 m2. Correlation analysis revealed that urea clearance is superior to creatinine clearance, and BUN is superior to serum creatinine concentration in the degree of relationship to renal digoxin clearance. Moreover, using partial correlation techniques, it is apparent that in these patinets digoxin clearance was significantly related to urine flow rate. These findings are compatible with the hypothesis that digoxin undergoes some degree of tubular reabsorption as well as filtration and secretion.

Adult↗
PubMed1975

Influence of congestive heart failure on blood vessels of lidocaine and its active monodeethylated metabolite.

The blood concentrations of lidocfaine and its active monodeethylated metabolite, monethylglycinexylidide (MEGX), were measured in 31 patients who were receiving infusiions of lidocaine intravenously. In 3 patients who were studied intensively, the elimination half-life of MEGX was 120 min, which was similar to the elimination half-life of lidocaine (139 min). An addition 3 patients demonstrated a higher ratio of the concentration in blood of MEGX to lidocaine, and the MEGX may have contributed, in 1 patient, to the central nervous system toxicity that occurred during the infusion. Elevated concentrations of MEGX in blood were associated with congestive heart failure (r equalto 0.5, p equal to 0.004). Our data suggest that the elimination of MEGX may be decreased in patients with depressed cardiac output and sympathomimetic compensation.

Adult↗
PubMed1975

Improved computer-assisted digoxin therapy. A method using feedback of measured serum digoxin concentrations.

Automated feedback control methods were applied to a medical problem, in a computer program that used measured serum digoxin concentrations (as feedback) to predict future concentrations and to achieve desired concentrations. The system was validated by comparing its ability with the corresponding ability of physicians to regulate digoxin dosage. The prospective, randomized study included 51 patients. In the presence of varying amounts of feedback (serum digoxin concentration) information, the computer always predicted future digoxin concentrations as accurately as did physicians. For both computer and physician, the decrease in the prediction errors when two concentrations were known against that when no concentrations were known was significant: mean absolute error decreased from 0.40 to 0.25 ng/ml for the physicians and from 0.45 to 0.27 ng/ml for the computer. Thus the computer system is capable of simulating and reproducing a sophisticated aspect of physician behavior: "learning" about individual patient responses. The computer achieved desired concentrations more accurately than did physicians, especially when two or more previous digoxin concentrations were abailable (mean absolute achievement error for computer, 0.28 ng/ml; for physicians, 0.50 ng/ml).

Achievement↗