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Biomedical subjects

N A Klitgaard

Publications and source records attributed to N A Klitgaard.

At least 91 records · Page 5Linked to original sources
PubMed1983

The characteristics of [3H]-ouabain binding to human lymphocytes.

The kinetic characteristics of [3H]-ouabain binding to human lymphocytes and mixtures of mononucleated cells, and the maximum [3H]-ouabain binding capacities of these cells were studied. The [3H]-ouabain binding was compatible with a single class of receptors with a high affinity for the drug. No signs of positive or negative cooperativity could be demonstrated. In six experiments with pure lymphocyte preparations, the association and dissociation rate constants were 3.08 +/- 0.34 X 10(4)/M/S and 1.58 +/- 0.50 X 10(-4)/S. The dissociation constant derived from equilibrium studies on lymphocytes was 0.68 +/- 0.21 X 10(-8) M, which was identical to that of mononucleated cells. In healthy subjects the maximum [3H]-ouabain binding capacities, which reflect the number of sodium/potassium pump sites were 43154 +/- 8037 molecules/cell (n = 25) in lymphocytes and 75474 +/- 6764 (n = 9) molecules/cell in mixtures of mononucleated cells. Direct determination of the [3H]-ouabain binding capacity of lymphocytes can be performed with acceptable accuracy and precision using 30 ml whole blood. Provided high cell purity, this method may be useful, when studying sodium/potassium pump function in clinical settings.

Humans↗
PubMed1983

Pharmacokinetics of 10-OH-carbazepine, the main metabolite of the antiepileptic oxcarbazepine, from serum and saliva concentrations.

After administration of 600 mg of the antiepileptic oxcarbazepine to 7 healthy volunteers, serum and stimulated saliva samples were collected for the next 72 h. Concentrations of 10-OH-carbazepine, the main metabolite of oxcarbazepine, were determined by an HPLC method. The time-concentration curves showed a median Tmax of 8 h followed by a plateau until 24 h indicating saturable kinetic processes. Based on the curves, the pharmacokinetic parameters were calculated. The half-life of 10-OH-carbazepine in saliva, 13.8 +/- 3.7 (SD) h, was significantly shorter than in serum, 19.3 +/- 6.2 (SD) h. The half-life of 10-OH-carbazepine in serum was inversely correlated to the free fraction, estimated by the ratio saliva/serum concentrations. Calculation of free fraction by this method showed that 53.1 +/- 14.4 (SD) % of 10-OH-carbazepine is unbound in serum. There was a good correlation (r = 0.914) between serum and saliva concentrations of 10-OH-carbazepine from 8-72 h after administration of oxcarbazepine. This finding indicates that saliva concentrations may prove useful, as has been shown for carbamazepine, in therapeutic monitoring of oxcarbazepine treatment.

Adult↗
PubMed1983

Changes in steady state digoxin pharmacokinetics during quinidine therapy in cardiac patients: influence of plasma quinidine concentration.

In seven cardiac patients on long-term digoxin therapy, digoxin kinetics were investigated - in the absence and presence of quinidine - after simultaneous administration of an oral digoxin dose and an intravenous 3H-digoxin bolus injection. From 3H-digoxin data quinidine was found to decrease both renal (from 1.19 +/- 0.35 to 0.86 +/- 0.21 ml/min./kg) (P less than 0.02) and extrarenal clearances of digoxin (from 0.85 +/- 0.24 to 0.49 +/- 0.23 ml/min./kg) (P less than 0.02), and to diminish the steady state distribution volume of the drug (from 6.78 +/- 1.23 to 5.63 +/- 1.64 l/kg) (P less than 0.02). Plasma half-life increased from 51.5 +/- 5.4 to 64.4 +/- 14.8 hrs (P less than 0.05), while urinary excretion half-life increased from 54.4 +/- 3.9 to 78.5 +/- 14.1 hrs (P less than 0.01). Pharmacokinetic parameters derived from plasma and urinary digoxin data showed similar changes during quinidine therapy. Reduction in renal 3H-digoxin clearance occurred at subtherapeutic plasma quinidine levels and was independent of plasma quinidine, whereas reductions in extrarenal 3H-digoxin clearance and 3H-digoxin distribution volume were positively correlated to plasma quinidine concentrations (P less than 0.05).

Creatinine↗
PubMed1982

The long-term effect of verapamil on plasma digoxin concentration and renal digoxin clearance in healthy subjects.

Single-dose investigations in healthy subjects have demonstrated substantial impairment of renal and extrarenal clearance of digoxin during coadministration of verapamil. A longitudinal study has been performed to assess the changes in digoxin disposition during long-term verapamil therapy. After one week of verapamil 240 mg/d mean plasma digoxin had risen from 0.21 +/- 0.01 ng/ml (SE) to 0.34 +/- 0.01 ng/ml(p less than 0.01), and renal digoxin clearance had fallen from 197.57 +/- 17.37 ml/min to 128.20 +/- 10.33 ml/min (p less than 0.001). These changes gradually subsided, and after six weeks, renal digoxin clearance had normalized and plasma digoxin had declined to 0.27 +/0 0.02 ng/ml (NS). The 24-h urinary recovery of digoxin increased from 46.46 +/- 3.23% before to 69.78 +/- 3.69% (p less than 0.001) after six weeks of verapamil co-administration, and this elevation persisted throughout the study. The verapamil-induced suppression of renal digoxin elimination disappears over a few weeks of drug exposure, whereas the inhibition of the extrarenal clearance of digoxin seems to persist.

Adult↗
PubMed1982

Overdosage of antidepressants: clinical and pharmacokinetic aspects.

Twenty-nine cases of self-poisoning with antidepressants (amitriptyline, imipramine, clomipramine, maprotiline, doxepine, nortriptyline, opipramol) were examined by frequent observation of CNS effects, heart rate, blood pressure and standard ECG, 24h-ECG-monitoring, measurement of systolic time intervals, EEG recordings and frequent measurement of serum levels of antidepressants and primary metabolites. None of the patients died. Maximum total serum antidepressant level (parent compound + desmethyl metabolite) ranged from 20 to 2200 micrograms/l, with concentrations above 500 micrograms/l in 11 cases. The serum amitriptyline concentration remained high for 3-4 days in some of the severely intoxicated patients and the decay curves were compatible with partly saturated elimination. A degree of unconsciousness and the occurrence of excitation and hallucinations were generally seen in cases with total serum antidepressant levels above 500 micrograms/l. Grand mal seizures occurred more frequently at high antidepressant levels, but could not be predicted from the EEG recordings. Increased heart rate and prolonged QRS- and QTc-intervals were significantly correlated with the total serum antidepressant level. 24 h-ECG-monitoring revealed no serious arrhythmias or instances of heart block. Hypotension was only seen initially in few patients. Systolic time interval measurements showed changes suggesting impaired myocardial performance (elevated PEP/LVET ratio) at intermediate (60-500 micrograms/l) but not high (greater than 500 micrograms/l) total serum antidepressant levels. Measurement of serum concentration in antidepressant intoxication is important for identification of patients with high serum levels and the corresponding risk of developing toxic reactions, and to exclude patients with a low concentration who do not require intensive observation.

Adult↗
PubMed1982

Effect of nifedipine on digoxin kinetics in healthy subjects.

Verapamil has been shown to reduce total-body digoxin clearance by 35% due to impairments of both renal and extrarenal clearances. Our study was undertaken to evaluate the influence of the related calcium antagonist nifedipine on single-dose kinetics. Nifedipine increased extrarenal clearance of digoxin from 1.09 +/- 0.30(SD) to 1.45 +/- 0.23 ml/min/kg (P less than 0.05) and reduced the total urinary recovery of the drug from 69.2% +/- 5.9(SD) to 64.3% +/- 5.2 (P less than 0.05). There were no significant changes in renal digoxin clearance, distribution, or biological half-life or in digoxin distribution volumes during nifedipine coadministration.

Adult↗
PubMed1981

Digoxin-verapamil interaction.

To explore a possible interaction between digoxin and verapamil, a single-dose kinetic study of digoxin was performed and then repeated after 10 days of verapamil treatment in eight healthy subjects. Verapamil diminished the apparent central distribution volume of digoxin from 0.83 +/- 0.25 to 0.64 +2- 0.17 l/kg (P less than 0.05) and reduced total body clearance of digoxin from 3.28 +/- 0.58 to 2.15 +/- 0.66 ml/min/kg (P less than 0.001) by impairing both renal and extrarenal clearance. Biological digoxin half-life rose from 38.6 +/- 8.5 to 50.5 +/- 8.3 hr (P less than 0.005). Reduction of renal clearance of digoxin may be due to inhibition of tubular secretion. The underlying mechanisms of extrarenal interaction are not known, but impaired hepatic degradation of digoxin induced by verapamil should be considered.

Adult↗
PubMed1979

Significance of the acetylation phenotype and the therapeutic effect of procainamide.

In order to estimate the relative anti-arrhythmic effect of procainamide and N-acetyl-procainamide, 18 randomly selected, patients with arrhythmia were divided into two groups; the first was treated with Pronestyl in the first half of the investigation period, followed by Duretter in the second half, and the second group began with Duretter and terminated with Pronestyl. The concentrations of procainamide and N-acetylprocainamide were measured twice a day during the steady state part of each treatment period. The acetylation phenotype of the patients was determined with sulfadimidine, and compared with the relative serum concentrations of procainamide and N-acetylprocainamide. N-acetylprocainamide was found to antagonize the action of procainamide.

Acetylation↗
PubMed1979

Gastrointestinal blood loss caused by controlled-release and conventional acetylsalicylic acid tablets.

Gastrointestinal blood loss has been studied following oral administration of the novel controlled-release acetylsalicylic acid tablet preparation Acetard and the instant-release acetylsalicylic acid tablet Magnecyl (Ph. Nord. 63). Acetard contains micro-encapsulated acetylsalicylic acid crystals having an in vitro release time of approximately 4 hours. The investigation was carried out as a two-part, randomized cross-over trial, and with a test dosage of either 1 g X 4 or 2 g X 2 per day, given to 10 and 14 male students, respectively, during two 5-day periods separated by a one week interval. The dosage of the plain formulation was maintained at 1 g X 4 daily in both parts of the investigation. Faeces were collected every 24 hours throughout the trial, covering a total of 4 weeks. Blood loss was measured using the 51Cr labelling technique. Acetard was found to cause statistically significantly less gastrointestinal blood loss as compared with the plain formulation, irrespective of whether Acetard was given twice or four times a day.

Adult↗
PubMed1978

Cellular and humoral indices of disease activity in inflammatory bowel disease.

In 51 untreated cases of ulcerative colitis and Crohn's disease some cellular (neutrophil alkaline phosphatase activity, neutrophil NBT reducing capacity, and neutrophil and plasma lysozyme activities) and humoral (serum orosomucoid and serum haptoglobin) indices of disease activity were quantitated. The most pronounced signs of disease activity, thus, were found in severe cases of ulcerative colitis. Combining lysozyme activities with other disease activity indices seems to facilitate the distinction between severe cases of Crohn's disease and ulcerative colitis. Beyond this the addition of the humoral indices seemed not to offer substantial help.

Adolescent↗
PubMed1977

Lysozyme in plasma and neutrophilic granulocytes in ulcerative colitis and Crohn's disease.

The concentration of lysozyme in plasma (P) and in neutrophil leucocytes (N) was determined by a turbidimetric method in 32 patients with ulcerative colitis (U.C.), 11 patients with Crohn's disease (C.D.), 9 patients with haemorrhagic proctitis, and 39 healthy volunteers. In active U.C., P was significantly elevated (p less than 0.05), whereas C.D. showed normal values. Corresponding N was significantly reduced in active U.C. (p less than 0.05) but normal in C.D. In calculating the ratio N/P, highly significant lower values were found in active U.C. (p less than 0.001) compared to normal levels in C.D. The high P in active U.C. is presumed to reflect an accelerated destruction of neutrophil leucocytes as well as an intensified turnover rate. The reduced N is probably attributable to an inhibited synthesis. The findings suggest that lysozyme determinations are valuable in be differential diagnosis of active U.C. and C.D.

Adolescent↗