Biomedical subjects

S Vozeh

Publications and source records attributed to S Vozeh.

78 records · Page 5Linked to original sources

PubMed1977

The influence of cigarette smoking and sex on theophylline disposition.

The effects of cigarette smoking and sex on theophylline clearance, elimination rate constant, and apparent volume of distribution were examined in 28 healthy, young adults given single oral doses of theophylline or aminophylline. Two-way analysis of variance showed no sex effect but a significant effect of smoking habit on theophylline clearance and elimination rate constant. Neither sex nor smoking had an effect on the apparent volume of distribution. The respective mean clearance, elimination rate constant, and volume of distribution were, in nonsmokers, 0.040 +/- 0.008 (SD) liter per hour per kg, 0.084 +/- 0.015 hr-1, 0.47 +/- 0.08 liter per kg; heavy smokers, 0.063 +/- 0.019 liter per hour per kg, 0.129 +/- 0.045 hr-1, 0.50 +/- 0.06 liter per kg; and ex-smokers, 0.051 +/- 0.10 liter per hour per kg, 0.108 +/- 0.025 hr-1, 0.49 +/- 0.08 liter per kg. Cigarette smoking appeared to induce theophylline metabolism as reflected by the mean theophylline half-life in smokers (5.4 hours) versus nonsmokers (8.3 hours). The effect of cigarette smoking on theophylline clearance may be an important consideration in the clinical use of the drug.

Adult↗

PubMed1975

[Proceedings: Studies on the digoxin resorption in patients with decompensated right cardiac insufficiency].

Digoxin absorption was investigated in 7 patients suffering from severe right cardiac failure. After successful treatment and disappearance of the symptoms of right cardiac failure, the study was repeated in the same patients. Tritium-labelled digoxin in a dose of 0.1 mg as a solution, and non-labelled digoxin as a 0.25 mg tablet, were given to the patients in the fasting state. Blood samples were taken at specified time intervals up to 120 h and the urine was collected during the same period. The concentrations of digoxin in plasma and urine were measured in a liquid scintillation counter. The unlabelled digoxin was estimated by radioimmunoassay. The concentrations obtained in the plasma and urine were used to compute pharmacokinetic parameters. There was no significant difference in the plasma concentration curves in severe right cardiac failure and after successful treatment, nor did the calculated pharmacokinetic parameters differ significantly. Inhibition of digoxin absorption in severe right cardiac failure therefore seems unlikely.

Digoxin↗

PubMedDate not supplied

Rapid prediction of individual dosage requirements for lignocaine.

The mean and standard deviation of lignocaine (lidocaine) pharmacokinetic parameters in a patient population were determined on the basis of 327 serum concentration measurements obtained in 42 patients treated for ventricular arrhythmias. The application of a Bayesian forecasting method, which uses the estimates of the population parameters and 1 or 2 serum concentration measurements as feedback information, was tested retrospectively in 17 of the 42 patients (group I, 32 levels), and prospectively in 10 additional patients (group II, 20 levels). With 1 individual feedback concentration, sampled 2 to 4 hours after the start of lignocaine infusion, serum concentrations at 12 and 24 hours could be accurately predicted. The prediction error (measured minus predicted concentration) ranged between -1.2 and +1.6 (mean -0.03) mg/L in group I, and from -0.7 to +1.5 mg/L (mean +0.13) mg/L in group II; the correlation coefficient of measured and predicted levels were 0.92 and 0.86, respectively. In contrast, a prediction of lignocaine concentrations in these patients using only population parameters without feedback was poor: range of the prediction error = -3.1 to +3.0 mg/L (mean = +0.001 mg/L, r = 0.63, groups I and II, n = 52). The results demonstrate that with the Bayesian forecasting technique, accurate assessment of individual dosage requirements can be obtained within a few hours after starting lignocaine therapy.

Adult↗

PubMedDate not supplied

Serum level monitoring of antibacterial drugs. A review.

Serum concentration measurements of antibacterial agents are increasingly used to optimise drug dosage regimens. However, this approach is only justified for drugs with a low therapeutic index and poor predictability of serum concentrations, such as the aminoglycosides, chloramphenicol and vancomycin, whereas the penicillins and cephalosporins can safely be applied well above their minimum inhibitory concentrations. Wide interpatient variation in distribution and elimination are the main reasons for the unpredictability of aminoglycoside serum concentrations. It has been shown that in patients with normal creatinine clearance, the apparent elimination half-life of gentamicin varies from 0.4 to 7.6 hours. The pharmacokinetics of the aminoglycosides are most adequately described by a 3-compartment open model where the slow terminal half-life reflects elimination from the deep tissue compartment. The accumulation of the aminoglycosides in this compartment, which includes the kidneys and inner ear, is probably an important factor in their potential toxicity in these organs. Careful serum level monitoring may reduce, but cannot totally avoid, the risk of side effects. However, maintenance of effective drug levels appears to be at least an equally important goal of aminoglycoside serum level monitoring. Chloramphenicol is also a potentially toxic antibacterial agent. Its therapeutic range is usually considered to be 15 to 25 mg/L. The most important side effects are the 'grey baby syndrome' and bone marrow toxicity. Chloramphenicol is metabolised to several microbiologically inactive products. It also shows wide interpatient variability of its pharmacokinetics, especially in young children, and serum levels should therefore be followed in these patients. Vancomycin, a highly effective agent for staphylococcal and enterococcal infections, may also exhibit nephrotoxic and ototoxic side effects. A well-defined therapeutic range has not yet been established but in view of its minimum inhibitory concentrations it seems reasonable to maintain vancomycin serum concentrations between 15 and 50 mg/L. Since this drug is excreted unchanged in the urine, serum levels should particularly be monitored in patients with impaired renal function. The advances in routine therapeutic drug monitoring are directly related to rapid developments in technologies associated with the quantification of these agents. Microbiological plate diffusion assays are now often replaced by more specific immunoassays (radioimmunoassay, enzyme immunoassay, and fluorescence immunoassay) and chromatographic techniques.

Aminoglycosides↗

PubMedDate not supplied

Feedback control methods for drug dosage optimisation. Concepts, classification and clinical application.

The concept of feedback control methods for drug dosage optimisation is described from the viewpoint of control theory. The control system consists of 5 parts: (a) patient (the controlled process); (b) response (the measured feedback); (c) model (the mathematical description of the process); (d) adaptor (to update the parameters); and (e) controller (to determine optimum dosing strategy). In addition to the conventional distinction between open-loop and closed-loop control systems, a classification is proposed for dosage optimisation techniques which distinguishes between tight-loop and loose-loop methods depending on whether physician's interaction is absent or included as part of the control step. Unlike engineering problems where the process can usually be controlled by fully automated devices, therapeutic situations often require that the physician be included in the decision-making process to determine the 'optimal' dosing strategy. Tight-loop and loose-loop methods can be further divided into adaptive and non-adaptive, depending on the presence of the adaptor. The main application areas of tight-loop feedback control methods are general anaesthesia, control of blood pressure, and insulin delivery devices. Loose-loop feedback methods have been used for oral anticoagulation and in therapeutic drug monitoring. The methodology, advantages and limitations of the different approaches are reviewed. A general feature common to all application areas could be observed: to perform well under routine clinical conditions, which are characterised by large interpatient variability and sometimes also intrapatient changes, control systems should be adaptive. Apart from application in routine drug treatment, feedback control methods represent an important research tool. They can be applied for the investigation of pathophysiological and pharmacodynamic processes. A most promising application is the evaluation of the relationship between an intermediate response (e.g. drug level), which is often used as feedback for dosage adjustment, and the final therapeutic goal.

Anesthetics↗

PubMedDate not supplied

Relative electrophysiological potencies of quinidine, 3-OH quinidine and quinidine-N-oxide in guinea-pig heart.

The relative potencies of the quinidine metabolites, 3-OH quinidine (3OHQ) and quinidine-N-oxide (QNO), to their parent drug, quinidine, were obtained electrophysiologically using guinea-pig hearts. The items examined were QT interval of local extracellular electrogram in a Langendorff's perfused heart, effective refractory period (ERP) and action potential duration at 90% repolarization (APD90) in the right papillary muscle. Quinidine (0.125-1 mg/l) and 3OHQ (0.5-4 mg/l) prolonged QT interval in a concentration-dependent manner and the relative potency of 3OHQ to quinidine was 0.25. The effect of QNO on QT interval within the range of concentration used (up to 8 mg/l) was small and the relative potency was 0.04 at the most. An apparent additive effect of 3OHQ to that of quinidine was revealed, but QNO of 4 mg/l has no effect on the concentration-effect relationship of quinidine for prolonging QT interval. These results were quite similar to those in humans reported previously. Quinidine (0.5-4 mg/l), 3OHQ (1-8 mg/l) and QNO (2-8 mg/l) prolonged APD90 in a concentration-dependent manner. These effects were accompanied by the prolongation of ERP in similar degrees. The relative potencies of 3OHQ to Q were 0.22 for APD90 and 0.27 for ERP and those of QNO were 0.087 for APD90 and 0.084 for ERP. Quinidine (10(-5) M) depressed the maximum upstroke of action potential (Vmax) in a frequency-dependent manner. 3OHQ of the same concentration also depressed it in the same manner to a much lesser extent and QNO had no effect. In conclusion, relative potencies of quinidine metabolites to quinidine for prolonging QT interval of local extracellular electrogram represent those to prolong APD90 and ERP, suggesting the relative potencies for antiarrhythmic activity in the same order. In the physiological range of concentrations of metabolites, 3OHQ may contribute to the antiarrhythmic effect of quinidine in an additive way, but QNO may have little effect when we take into account the fact that the free fraction of 3OHQ is 2.5 times that of quinidine.

Action Potentials↗