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S Vozeh

Publications and source records attributed to S Vozeh.

At least 73 records · Page 4Linked to original sources
PubMed1981

[Pharmacokinetic of benzodiazepines in old age].

The elimination half-life of chlordiazepoxide and diazepam increases with age, and this may cause prolongation of action after a single dose and delayed accumulation on multiple dosing in elderly patients. Since the total body clearance of chlordiazepoxide is also reduced, higher steady-state serum concentration is to be expected in patients over 60 years of age. Desmethyldiazepam, one of the active metabolites of diazepam and chlordiazepoxide with a long elimination half-life, also shows impaired elimination in old persons. Prolongation of half-life without changes in total body clearance has been demonstrated for nitrazepam and temazepam. In contrast, oxazepam and lorazepam do not show clinically significant changes of pharmacokinetics with age. The clinical implications of the different pharmacokinetic characteristics are discussed.

Adult↗
PubMed1981

Predicting individual phenytoin dosage.

Most previously suggested methods for predicting phenytoin dosage from steady-state drug levels (Cpss) measured in the clinical setting fail to fully exploit all relevant (population) information. A bayesian prediction method, applicable to any drug, is available. It appropriately combines all types of information. In this paper, we compare the Bayesian method as applied to phenytoin to two other prediction methods (and a baseline, nonfeedback one). Actual doses are compared to predictions in 49 patients. Each method is optimized, as far as possible, for the test data. The comparison favors the Bayesian method. Since each of the other prediction methods for phenytoin can be shown to be a theoretically suboptimal special case of the Bayesian one, the superiority of the latter may be a general phenomenon. Because the pharmacokinetic model linking steady-state phenytoin levels and dosage is so simple, a good approximation of the general Bayesian method can be implemented as a graphical device, or as a program for a programmable calculator. We present and describe both of these approximations.

Feedback↗
PubMed1980

Nomographic estimation of time to reach steady-state serum concentration during phenytoin therapy.

The time to reach steady-state on phenytoin therapy depends on the dose and the pharmacokinetic parameter of the individual patient. A nomogram is presented to help the physician to decide whether a measured serum concentration of phenytoin can be regarded as being within 20% of the steady-state level. The nomogram is based on the pharmacokinetic parameters of phenytoin reported for adult patients.

Humans↗
PubMed1980

Rapid prediction of steady-state serum theophylline concentration in patients treated with intravenous aminophylline.

In 15 acutely ill asthmatics the steady-state serum theophylline concentration was predicted by the method of Chiou et al. using two serum concentration measurements obtained 1 and 5 h after starting a continuous infusion of aminophylline. Two theophylline assays with different precision characteristics were compared. With a precise HPLC-assay the prediction was excellent: prediction error (predicted minus measured concentration) = -0.22 +/- 1.97 mg/l (mean +/- SD); r = 0.922. When the theophylline concentration was determined by a rapid enzyme immunoassay of lower precision, but convenient for clinical use, the prediction was less accurate (prediction error = 0.58 +/- 3.88, r = 0.852). However, it was still clearly superior to dosing recommendations based on the population average of theophylline clearance, even after taking into consideration the effect of smoking, congestive heart failure and cirrhosis (prediction error = 3.62 +/- 13.36, r = 0.560). As employed in this study, the method may be useful in helping the physician to choose the optimal dose in severely ill asthmatics.

Aminophylline↗
PubMed1980

Predictability of phenytoin serum levels by nomograms and clinicians.

On the basis of a reliable steady state phenytoin serum concentration on one (lower) dose, the serum concentration on a second (higher) dose was predicted in 28 patients (32 levels) by two previously reported nomograms and 3 physicians who had clinical experience with phenytoin therapy. Both nomograms and all 3 physicians on the average underestimated the serum concentration on the higher dose. Except for 1 physician, this bias was statistically significant (p < 0.05). The mean and SD of the prediction errors (difference between predicted and measured serum concentration) were -2.2 +/- 4.2 and -3.1 +/- 3.6 for the two nomograms and -1.0 +/- 4.0, -2.1 +/- 4.1 and -1.8 +/- 4.2 for the 3 physicians, respectively. Thus, independent of the method used, there was a large uncertainty in the prediction; the approximate 68% confidence interval of the prediction error (mean +/- SD) was almost as large as the therapeutic range of the drug. Because prediction of phenytoin serum levels based on one serum concentration measurement was found unreliable in this study, it is proposed that every patient whose dose had been increased should be under close observation until a new steady state has been confirmed.

Adult↗
PubMed1979

[Delayed elimination of aminoglycoside antibiotics: importance for clinical use].

In 7 patients the elimination of amikacin (4), tobramycin (1) and gentamicin (2) in serum and urine was measured over several days after cessation of therapy. All three aminoglycosides showed multicompartmental pharmacokinetics with a terminal half life ranging between 46 and 150 hours. Using computer simulations, it is shown that slow drug accumulation in the body is to be expected during multiple dose therapy. Therefore, the indiscriminate use of these drugs should be avoided and the duration of therapy kept as short as possible.

Amikacin↗
PubMed1979

Absorption of digoxin in severe right heart failure.

The absorption of digoxin has been investigated in 8 patients before and after successful treatment of severe right heart failure. 3H-digoxin 0.1 mg as a solution, and un-labelled digoxin 0.25 mg as a tablet, were given to fasted patients. Blood samples were taken at various time intervals up to 120 hours and urine was collected over the same period. The concentrations of labelled digoxin in plasma and urine were measured in a liquid scintillation counter, unlabelled digoxin was estimated by radioimmunoassay, and various pharmacokinetic parameters were calculated. There was no significant difference in the plasma concentration curves in severe right heart failure and after its successful treatment, nor did any of the calculated pharmacokinetic parameters change significantly. Therefore, inhibition of the absorption of digoxin appears unlikely. In an additional study to estimate absolute bioavailability two different groups of patients in severe right heart failure were given 3H-digoxin 0.1 mg or unlabelled digoxin 0.25 mg i.v. and the pharmacokinetic parameters were compared with those from the previous study. The bioavailability of the 3H-digoxin solution and of the digoxin tablet were in the same range as values previously published for healthy volunteers, and patients both with and without cardiac failure.

Biological Availability↗
PubMed1979

Simultaneous modeling of pharmacokinetics and pharmacodynamics: application to d-tubocurarine.

We propose a model of drug pharmacodynamic response that when integrated with a pharmacokinetic model allows characterization of the temporal aspects of pharmacodynamics as well as the time-independent sensitivity component. The total model can accommodate extremes of effect. It allows fitting of simultaneous plasma concentration (Cp) and effect data from the initial distribution phase of drug administration, or from any non-equilibrium phase. The model postulates a hypothetical effect compartment, the dynamics of which are adjusted to reflect the temporal dynamics of drug effect. The effect compartment is modeled as an additional compartment linked to the plasma compartment by a first-order process, but whose exponential does not enter into the pharmacokinetic solution for the mass of drug in the body. The hypothetical amount of drug in the effect compartment is then related to the observed effect by the Hill equation, a nonlinear sigmoid form. Nonlinear least-squares data fitting is used for parameter estimation. The model is demonstrated on two different sets of Cp and effect data for the drug d-tubocurarine (dTC). In 7 normal subjects, the (mean +/- SD) rate constant for equilibration of dTC effect (paralysis) and Cp is 0.13 +/- 0.04 min-1 and the (mean +/- SD) steady-state Cp required to produce 50% paralysis is 0.37 +/- 0.05 microgram/ml.

Adult↗
PubMed1979

Multicompartment pharmacokinetics of netilmicin.

The pharmacokinetics of a single dose of netilmicin (NM) was studied in 6 healthy volunteers. Elimination of the drug was followed in serum and urine for 24 h and 72 h, respectively. NM concentrations were measured with a modified radioenzymatic assay. A three compartment open model was employed to calculate the pharmacokinetic parameters. Following the rapid initial distribution, biphasic elimination with half lives of 1.99 (t 1/2 beta) and 36.89 h (t 1/2 gamma) was demonstrated. Measurable amounts of NM were excreted in the urine for up to 72 h. The volume of distribution at steady-state (Vdss) of 0.68 l/kg was 3 to 4 times larger than previously reported for this antibiotic. NM plasma clearance was 91 ml/min and the renal clearance was 67 ml/min. The data indicate that on repetitive dosing the amount of drug in the body would be considerably underestimated if the prolonged terminal elimination phase were not taken into account. During prolonged treatment, accumulation of NM in renal and other tissues is likely to occur, as has been described for other aminoglycosides. The possible consequences of this pharmacokinetic behaviour are discussed.

Adult↗
PubMed1978

Changes in theophylline clearance during acute illness.

Three patients demonstrated twofold to threefold changes in total-body theophylline clearance during the course of a single hospitalization for an acute illness. These changes paralleled the changes in the patients' clinical status. Theophylline clearance decreased in one patient with worsening airway obstruction, whereas clearance increased in one patient with resolving pneumonia and in one patient with improving congestive heart failure. Total-body theophylline clearance may be unstable in acute, severe illness. Close monitoring of plasma theophylline concentration in such situations will allow appropriate dose adjustments to be made and is, therefore, indicated.

Acute Disease↗
PubMed1978

Saliva lithium concentrations in the management of lithium therapy.

To define conditions under which saliva lithium carbonate concentrations can be used as a guide in lithium therapy, serum (Cp) and saliva (Cs) concentrations were determined simultaneously under different circumstances in 12 patients receiving lithium, and the effect of seven variables for example, (sex, saliva flow rate) on the Cp:Cs ratio was examined. The average ratio was 0.57 if saliva was collected in the morning before breakfast and 0.45 otherwise. The Cp:Cs ratio was found to vary much more between individuals than within an individual. We propose a method that minimizes the effect of the interindividual variation on the error in the prediction of Cp from Cs by using one or two measured Cp:Cs ratios to adjust the individual ratio. Using this technique the Cs may be useful as a predictor of the Cp in monitoring lithium therapy.

Aged↗
PubMed1978

Theophylline disposition in acutely ill hospitalized patients. The effect of smoking, heart failure, severe airway obstruction, and pneumonia.

Theophylline disposition (clearance, volume of distribution, and half-life) was measured in 31 normal volunteers and 26 acutely ill patients with airway obstruction within 24 hours of hospital admission and again when intravenous aminophylline was discontinued 2 to 10 days later. Sex, age, race, the diagnosis of asthma, and the diagnosis of chronic bronchitis were not significantly correlated with clearance. Clearance was significantly increased in smokers and significantly decreased in patients with congestive heart failure, pneumonia, and severe bronchial obstruction. The volume of distribution was not correlated with these variables. Within 24 hours of admission, the mean clearance in our patients without congestive heart failure or pneumonia was 44.5 ml per hour per kg of body weight, 40 per cent less than the value on which the widely used 0.9 mg per kg per hour dosage is based. The unexplained interindividual variability of clearance was significantly higher amont patients than control subjects, but intraindividual variability in clearance was not different in these 2 groups after correction for the effects of smoking, congestive heart failure, and so on. Large variability in clearance among patients makes the plasma theophylline concentration resulting from any dosage relatively uncertain. Based on the the results of this study, recommendations are made concerning theophylline dosage computation, and the clinical circumstances calling for determination of plasma theophylline concentrations.

Acute Disease↗