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Biomedical subjects

H M von Hattingberg

Publications and source records attributed to H M von Hattingberg.

At least 19 recordsLinked to original sources
PubMed1993

Pharmacokinetics of linsidomine (SIN 1) after single and multiple intravenous short infusions in patients with renal insufficiency.

Pharmacokinetic measurements were performed in two groups of patients with coronary heart disease (CHD) after single and multiple dosing of 2 mg linsidomine (SIN 1). The drug was administered by intravenous short time infusion in 12 CHD-patients with renal insufficiency (RI group, Clcr: 11 +/- 6 ml/min) and in 12 CHD-patients with normal kidney function (control group, Clcr: 88 +/- 22 ml/min). The measurement of plasma concentration time courses of total SIN 1C (SIN 1 + SIN 1C) was found to be suitable for an estimation of the SIN 1C related half-life of the terminal phase (t50% = 1.5 +/- 0.5 h), as SIN 1 was eliminated from plasma rapidly (t50% = 12 to 20 min). Furthermore, the mean total SIN 1C plasma profiles were equal after single and multiple administration of the drug giving evidence that SIN 1C is not accumulating during repetitive dosing of SIN 1 in patients with renal disease. The mean maximum renal fraction of total SIN 1C excretion of RI-subjects (fe = 0.8 +/- 0.8% of dose) was significantly different from the corresponding mean value of the control group (fe(N) = 5.8 +/- 5.1% of dose). No differences were found for fe and fe(N) between day 1 and day 4. As SIN 1 is degraded in plasma very rapidly and as SIN 1C is cleared mainly extrarenally, any restrictions concerning repetitive SIN 1 dosage regimen should not be considered for CHD-patients with renal failure.

Adult↗
PubMed1992

Water: mechanism of oral rehydration, water deficiency = deficiency in salt.

UNICEF, the United Nations International Children Emergency Funds, has staged an enormous program to improve children's health conditions in the developing countries. One extremely fruitful field of engagement was, and still is, the treatment of dehydration. Oral rehydration therapy (ORT) has reluctantly been accepted in the industrialized countries. From clinical observations, we have gained a new understanding of known pathophysiological principles. Dehydration most often is a result of diarrhea, and therefore oral rehydration therapy is mostly referred to in the context of infections of the digestive system. We discuss additional causes of dehydration and its immediate and secondary consequences. We demonstrate not only that, but why and how, a very simple, inexpensive regimen is beneficial and effective in the treatment of dehydration. Without consideration of sodium deficit, understanding will fail, and treatment will remain ineffective.

Adolescent↗
PubMed1986

Mean residence time.

The definition of mean residence time in the strict sense of mathematical statistics is deduced. It is demonstrated that the area-normalized concentration time curve is an estimate of the probability density function for residence times of drug molecules in the pharmacokinetic system, provided that the area under the concentration-time profile is proportional to the total amount eliminated from the system. Criticisms (8) on the determination of the mean residence time are refuted. The linearity of pharmacokinetic systems is defined, based on the statistical interpretation of these systems.

Humans↗
PubMed1985

High performance liquid chromatographic determination of moxalactam in human plasma and cerebrospinal fluid.

A sensitive and reproducible method for the measurement of moxalactam in plasma and cerebrospinal fluid is described. Plasma proteins were removed by precipitation with ice-cold methanol at pH 5.6 and centrifugation. The supernatant was analysed by HPLC on a mu-Bondapack/phenyl column, with a mobile phase of acetonitrile/water/PIC Reagent A (20/80/1), and detection at 280 nm. The calibration curve was linear for plasma concentrations from 10 micrograms/ml to 60 micrograms/ml. Reproducibility was 4.7% (coefficient of variation) for within-day analysis and 13.8% for day-to-day analysis. Plasma concentrations in 9 moxalactam-treated patients with severe infections ranged from 0.9 micrograms/ml to 409 micrograms/ml. Individual pharmacokinetic parameters were calculated using a personal computer. In selected cases moxalactam concentrations were also determined in cerebrospinal fluid and tracheal aspirates.

Child↗
PubMed1984

Moment analysis in vivo and in vitro.

Moments are quantities that can be calculated either directly from empiric observations or from model equations that describe observed time-dependent events. The analysis of empirically obtained moments provides insight into the mean duration and into the time profile of the underlying processes. The rules of their assessment and analysis are the same for pharmacokinetic and for pharmaceutical observations. Examples are given that show the power of moment analysis in pharmacokinetic experiments in vivo and in pharmaceutical dissolution testing in vitro. The method can be used for evaluation of in vivo/in vitro correlations in biopharmaceutics.

Animals↗
PubMed1983

[Pharmacokinetic aspects of excretory urography in children].

Contrast media able to pass through the kidney were a major advance in the field of radiodiagnostics. Excretory urography is usually performed using metabolically-inactive substances which accumulate in the kidney and kidney-pelvis. A two-compartment model has always been used so far for pharmacokinetic evaluation of this. However, in doing so, the kidney pelvis was not taken in account. A further compartment was therefore added to this model which enables all the physiological processes demonstrated by excretory urography to be included in the evaluation. With this model, blood and urine levels can be used at the same time to calculate pharmacokinetic variables, as shown in 6 pediatric patients. In addition to the cumulative excretion of urine and blood levels of the contrast medium, the concentrations of the latter in the renal pelvis are shown. Particular attention is paid to the effects of two important factors in investigations using contrast medium--diuresis and total body fluid volume.

Adolescent↗
PubMed1982

In vitro--in vivo correlation, a time scaling problem? Basic considerations on in vitro dissolution testing.

The profile of cumulative amount released from a solid dosage form, observed in an in vitro liberation apparatus, represents the cumulative frequency of the residence times of drug molecules in the galenic formulation. The profile of release over time is usually affected by the dissolution models as well as by the experimental conditions. Such differing dissolution curves may become superimposable by a simple linear transformation of the time base. This is clearly demonstrated by two completely different retard formulations, film coated pellets and an erosible matrix tablet, which were tested in two dissolution apparatus, the Sartorius dissolution model and the USP-Paddle model. The parameters used in the transformation of the time base can be evaluated from the statistical moments of the residence times; the moments themselves are calculated from the cumulative frequency functions. The term "equivalence" of dissolution profiles is defined and discussed. The outlined considerations and methods are immediately transferable to the comparison of in vitro and in vivo liberation conditions.

Biopharmaceutics↗
PubMed1981

[Hypomagnesemic coma during therapy of septicaemia in a patient with acute lymphoblastic leukemia. (author's transl)].

During induction therapy of acute lymphoblastic leukemia a 10 year old boy developed a hyperuremic nephropathy and subsequently a staphylococcal septicemia at the beginning of the 3. week. Specific treatment was started leading to severe hypomagnesemia and generalized seizures with coma for 30 hours, which finally responded to magnesium replacement. The possible additive effect of nephropathy, gentamicin, and furosemide due to urinary loss of magnesium is discussed and should encourage further observations.

Child↗
PubMed1980

[Pharmacokinetic and clinical studies with sisomicin in paediatrics (author's transl)].

Pharmakokinetic and clinical investigations were carried out with sisomicin, one of the newer aminoglycoside antibiotics, in 40 children aged from seven days to ten years. Serum concentrations were determined in 35 children 1/2, 1, 2, 4 and 6 hours after i. m. injection of 1.0 mg sisomicin/kg body weight. The average peak serum levels were 2.48 mg/l in children under three months and 3.58 mg/l in children between seven months and ten years. Renal elimination in newborns is delayed in comparison to older infants and children; the distribution volume of the central compartment diminishes with increasing age. The effect of these two counteracting tendencies is that renal clearance remains constant in the age groups investigated, however the frequency of drug administration must be adjusted according to age. During an average treatment period of ten days adequate serum concentrations between 3.1 mg/l and 6.2 mg/l one hour after injection could be achieved with dosages adjusted to age and body weight. Clinical results were good: 18 out of 20 children could be cured clinically, and 20 out of 21 isolated infectious agents were eliminated. There were no problems in local and systemic tolerance.

Bacterial Infections↗
PubMed1980

The pharmacokinetic basis of optimal antibiotic dosage.

Pharmacokinetic parameters play an important part in the design of an optimal dosage schedule for a drug. These parameters are only of use to the clinician if they can be obtained reliably and without too much experimental or mathematical effort, and their predictive value is independent of elaborate pharmacokinetic models. The three cardinal parameters of clearance (CI), total volume of distribution (Vss) and mean time (T), are defined and different methods are described for their assessment in clinical practice. A more operational method for estimating T than the one recorded in the literature is recommended. The value of this new method is demonstrated by means of an evaluation of data on gentamicin from the literature which have not already been analysed pharmacokinetically, and a comparison with results obtained by classical and more costly methods.

Anti-Bacterial Agents↗
PubMed1980

[Pharmacokinetic analysis of the fluctuation in digitalis bloodlevels during oral therapy with beta-methyldigoxin in children with heart insufficiency (author's transl)].

In five children with insufficiency of the heart the blood digitalis-digoxin level was monitored by drawing blood 5 times daily over a period of 7 days, starting from the first day of digitalisation. The dosage aimed at a mid-rate attainment of the plateau concentration in the blood. Digitalis blood levels were determined by a commercial radioimmunoassay. The blood level curves were simultaneously adjusted over the whole period, with the aid of a self-developed programme for tablecacultators, so that the considerable fluctuations of blood levels could be exhibited. The so adjusted curves were also pharmacokinetically analysed. Our data are in good agreement with the literature. The total clearance was significantly below that of adults. The total amount of digoxin in the whole organism, as calculated and represented graphically, changed less significantly, but was clearly higher in the first days of the mid-rate digitalisation than during the steady state.

Administration, Oral↗