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L Dettli

Publications and source records attributed to L Dettli.

At least 19 recordsLinked to original sources
PubMed1986

Benzodiazepines in the treatment of sleep disorders: pharmacokinetic aspects.

In order to avoid after-effects during the day, slowly eliminated hypnotic agents should not be used in the treatment of sleep disorders. It has become customary to separate long-acting from short-acting benzodiazepines and to use the (terminal) half-life as the principle of classification. This approach is only justified, however, in the case of quickly absorbed benzodiazepines that have no pharmacologically active metabolites and that exhibit one-compartment disposition kinetics. In contrast, the duration of action of benzodiazepines characterized by marked two-compartment disposition kinetics can only be estimated correctly when the potency and all relevant kinetic parameters of the drug preparation and its pharmacologically active metabolites are considered.

Anti-Anxiety Agents↗
PubMed1984

Problems and pitfalls in estimating average pharmacokinetic parameters.

The problems of obtaining optimal average parameter estimates (APE) from experimental pharmacokinetic data are considered. Four different approaches, three parametric and one non-parametric tests, are compared, using selected individual alcohol concentration data. Pooling the raw data for estimating APE can obscure individual pharmacokinetic characteristics, whereas averaging individual parameter estimates (IPE) exposes unique statistical problems. Furthermore, careful consideration should be given to weighting procedures. The advantages and shortcomings of all four methods are discussed. It is concluded that none can be considered as a universally applicable statistical method in view of the purpose for which the information, derived from a set of data, e.g. an alcohol-kinetic study, is required.

Computers↗
PubMed1984

The pharmacokinetics of alcohol in human breath, venous and arterial blood after oral ingestion.

The concentration-time profile of ethanol in breath air (AAC), arterial (ABAC) and venous blood (VBAC) of human volunteers was studied after four different oral doses of absolute alcohol--0.5, 0.75, 1.0, and 1.25 g/kg body weight. Seventy-eight single dose experiments were carried out in 42 subjects. In all 78 studies AAC was measured and VBAC was estimated simultaneously in blood collected from a cubital vein of 36 volunteers. Arterial blood, too, was collected from 8 subjects from a catheter in a brachial artery. All blood alcohol concentrations were analysed independently by gas chromatography (GLC) and an enzymatic (ADH) method. A one-compartment open model with first order absorption and pseudo-zero-order elimination was employed to calculate the pharmacokinetic parameters. The average values for the first order absorption rate constant (ka) ranged from 2.2 to 3.1, from 2.4 to 2.6 and from 1.0 to 1.7 h-1 for ACC, ABAC and VBAC, respectively. The pseudo-zero-order elimination rate constant (beta) was 0.17 to 0.18, 0.21 to 0.22 and 0.26 to 0.27 g X 1(-1) X h-1, respectively. During absorption ABAC tended to be higher than VBAC, peaking at a higher level (Cmax) and with a shorter time to peak (tmax) until an arterio-venous concentration equilibrium was reached, whereafter VBAC remained above ABAC. Although there was a close relationship between AAC, ABAC and VBAC during elimination, AAC closely followed the pattern of ABAC during absorption and tended to deviate from VBAC. AAC, therefore, is a much better predictor of ABAC during absorption than VBAC.

Absorption↗
PubMed1977

One-dose and multiple-dose kinetics of minocycline in patients with renal disease.

Kinetic analysis of minocycline concentrations in plasma and urine resulted in the following findings: In normal subjects the biological half-life is about 17 hours after the first dose and 21 hours after repeated administration. The renal drug clearance is only about 8% of the overall plasma clearance which is independent of renal function with a mean value of 47 ml/min. The fraction of the absorbed dose eliminated unchanged in the urine is only 9--19%. As a consequence the elimination rate of the drug is practically independent of renal function and decreases only 9--19% in anuric patients. The renal drug clearance depends linearly on renal function. The gastro-intestinal bio-availability of minocycline from the coated tablet preparation is incomplete. The cumulative behaviour of the drug corresponds to the kinetic parameters determined after repeated administration. It is suggested that the usual dosage regimen should be used in patients with renal disease.

Adult↗
PubMed1977

[Capacity limited pharmacokinetics, a mechanism of drug toxicity (author's transl)].

In the past drug elimination was described mainly by two different laws. Zero-order kinetics postulates that the speed of elimination be constant and independent of drug concentration; in first-order kinetics which describes satisfactorily the elimination of all drugs except ethyl alcohol it is assumed that the speed of the elimination is proportional to the plasma drug concentration. This can only be interpreted biologically in the case of polar drugs eliminated by diffusion or filtration. Non-polar drugs, however, bind reversibly to macromolecules such as albumin and enzymes. This means that elimination should be saturable as predicted by the law of mass-action. Saturation phenomena have clearly been demonstrated with several drugs eliminated by tubular and biliary secretion, or by enzymatic transformation. It is shown that zero-order and first-order kinetics are consequences of the validity of the mass-action law in two extremely different drug concentration ranges. When the affinity between drug and biological macromolecules is high the possible clinically relevant consequences are abnormal drug accumulation and drug interactions such as mutual displacement from the plasma albumin binding sites, inhibition of active drug transport and metabolism, or enzyme induction.

Animals↗
PubMed1976

Drug dosage in renal disease.

Based on the well known linear relationship between the overall drug elimination rate constant and the endogenous creatinine clearance, it is shown how individual drug elimination parameters in patients with renal disease can be estimated from the patient's creatinine clearance or serum creatinine concentration. By means of a simple nomogram the elimination rate fraction is determined which describes the elimination rate of the drug as a fraction of its normal elimination rate constant. Based on the estimated elimination rate fraction the dosage regimen in the patient with renal disease is individually modified according to pharmacokinetic principles. At present the described method can be used with 45 different drugs.

Creatinine↗