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Biomedical subjects

H U Schulz

Publications and source records attributed to H U Schulz.

At least 91 records · Page 5Linked to original sources
PubMed1987

Absolute bioavailability of theophylline from a sustained-release formulation using different intravenous reference infusions.

The effect of different intravenous infusions on the absolute bioavailability of theophylline from a sustained-release formulation has been investigated. Oral administration of 750 mg theophylline (2 capsules Euphylong 375) was referenced to intravenous aminophylline infusions corresponding to 506 mg theophylline over 8 h (63 mg.h-1) in Study 1, and to 749 mg theophylline over 14 h in Study 2. A reduction in the infusion rate from 69 to 33 mg.h-1 was made in Study 2 after 8 h in order to mimic the concentration/time profile of the oral formulation as closely as possible. The absolute bioavailability was 100 (89, 115)% in Study 1 and 88 (73, 105)% in Study 2. The lower clearance values and, as a consequence, the lower bioavailability ratios observed with the higher intravenous dose, although not significant, indicate that the absolute bioavailability of theophylline might appear to depend on the choice of the intravenous reference standard.

Adult↗
PubMed1987

Effect of drug intake prior to or after meals on serum theophylline concentrations: single-dose studies with Euphylong.

Three separate single-dose, randomized, cross-over studies in normal, healthy volunteers were performed to investigate the possible influence of drug intake in relation to concomitant food intake and of different dietary habits such as cold and hot evening meals on the bioavailability of theophylline from Euphylong. Euphylong is a new, pH- and rpm-independent theophylline formulation designed for once-daily administration in the evening. The results obtained show that the timing of drug intake, in relation to concomitant food intake, has no influence on the bioavailability of Euphylong. Under equicaloric conditions, a 10% decrease in AUC and a 20% decrease in Cmax is observed when Euphylong is administered after a hot evening meal compared with a cold evening meal. Viewed against the dramatic changes in bioavailability of up to 100%, which have been observed for certain other sustained-release theophylline formulations, these minor changes for Euphylong are negligible and without clinical relevance.

Adult↗
PubMed1987

Comparison of steady state serum theophylline concentrations in healthy volunteers after dosing with Euphyllin retard and PulmiDur.

In a randomized cross-over study, theophylline serum levels were compared over a 12-h dosing interval after repeated administration of Euphyllin retard and PulmiDur to 18 healthy male volunteers. Although both preparations are sustained-release formulations they differ in the systems used and in the state of hydration of theophylline. Two tablets each of Euphyllin retard or one tablet PulmiDur plus one tablet PulmiDur forte were administered in an identical dosing scheme always before food intake. The mean value curves of theophylline serum levels obtained at steady state clearly demonstrate the marked sustained-release properties of both preparations. The relative bioavailability of Euphyllin retard vs. PulmiDur calculated from the individual ratios of the dose adjusted AUCs was 96(83-111)%, results being given as geometric mean and 95% confidence limits. Hence Euphyllin retard is equivalent to PulmiDur with regard to the extent of absorption.

Adult↗
PubMed1986

Effects of development, aging, and renal and hepatic insufficiency as well as hemodialysis on the plasma concentrations of albumin and alpha 1-acid glycoprotein: implications for binding of drugs.

The concentrations of total proteins, albumin, alpha 1-acid glycoprotein (AGP), and nonesterified fatty acids (NEFA) were measured in the serum of 21 newborn infants and 13 children, aged 1-13 months, and in the plasma of 31 volunteers, 25 patients with renal failure, 27 patients with cirrhosis, 39 uremic patients undergoing hemodialysis, and 20 elderly subjects. The concentration of albumin in the volunteers was higher than in all other groups. The concentration of AGP in the volunteers was higher than in newborn infants but lower than in elderly subjects, patients with renal failure, and those with chronic uremia. The concentration of NEFA in volunteers was higher than in newborn infants and patients with renal failure and lower than in elderly subjects and patients with cirrhosis.

Age Factors↗
PubMed1986

Production and characterization of antibodies to rat pancreatic acinar cells.

The contribution of immunologic noxae to the damage of the cells and the induction of autodigestion in the course of acute pancreatitis in rats should be regarded. The isolation of intact acinar cells from rat pancreas offers a new approach to a more specific antiserum being directed against antigens at the outside of the cell membrane. Proof of circulating antibodies was performed using the indirect immunofluorescence reaction method (IFAR). A defined membrane fluorescence was observed at the surface of the acinar cells in vitro and a fluorescence at the septa of lobules marking the borders of acini in vivo.

Acute Disease↗
PubMed1986

Once daily theophylline: multiple-dose comparison of an encapsulated micro-osmotic system (Euphylong) with a tablet (Uniphyllin).

In a randomized, multiple-dose, cross-over study, serum theophylline concentrations (STC) were compared in 12 healthy volunteers for 24 hours after the first and seventh administration of two sustained-release formulations. The preparations tested were the new encapsulated micro-osmotic system Euphylong (E) and the tablet Uniphyllin (U). Daily doses of 800 mg were administered at 7 p.m., half an hour after a standardized evening meal. The relative bioavailability of E with respect to U under steady-state conditions is 93 (83-105)%. In contrast to U, E markedly truncates the high peak concentrations and leads to a sustained, plateau-like concentration throughout the night. Therefore prediction of individual maximum serum levels becomes possible for E on the basis of one blood sample taken in the morning. The significantly improved in vivo performance of E in comparison with U is reflected in a 50% reduction of the swing, a 60% increase in the plateau time, and a substantial reduction of theophylline-specific side effects such as nausea, palpitations and increased diuresis.

Biological Availability↗
PubMed1986

Acute pancreatitis--a quantification of dynamics at clinical and radiomorphologic levels.

To quantify the dynamics of acute pancreatitis in a prospective clinical study on 108 patients, clinical and computed tomographic classifications were performed at days 1, 3 and 6 after admission. Sixty-two percent of the patients revealed a variable clinical staging at the times considered. Progredience of pancreatic necrosis was found in 20 of the 55 patients subjected to radiomorphologic investigations. Comparison between clinical and CT findings showed an increase in the agreement of both assessments from 69 percent (day 1) to 85 percent (day 6). Despite this high-level agreement in some patients both findings diverged remarkably. Acute pancreatitis is discussed as an interplay of necrobiosis and the "compensatory capacity" of the organism, with clinical findings acting as an indicator of the overall state of this struggle.

Acute Disease↗
PubMed1985

Determination of the theophylline solubilizer salicylamide-O-acetic acid in serum and urine using high-performance liquid chromatography.

A high-performance liquid chromatographic method for the determination of the theophylline solubilizer salicylamide-O-acetic acid has been developed in the range 0.5 to 10 microg/ml for human serum and 5 to 400 microg/ml for urine. Reversed-phase ion-pair chromatography was employed with tetrabutylammonium hydrogen sulphate as counterion and 2-nitrophenylacetic acid as internal standard. Preliminary pharmacokinetic single-dose studies show that the sensitivity and the selectivity of the assay are adequate to measure lower concentrations in the late beta-phase.

Journal Article↗
PubMed1984

Differences in steady-state plasma levels between aminophylline and theophylline sustained-release micropellets after repeated circadian dosing.

In a randomized double-blind, cross-over study, theophylline plasma levels were compared over 24 hours after repeated administration of aminophylline and theophylline sustained-release formulations to 12 healthy volunteers. Although both preparations were capsules containing micropellets, and although they were administered in an identical circadian dosing scheme (1 capsule at 8:00 a.m., 2 capsules at 10:00 p.m.), marked differences in theophylline plasma levels were found. Whereas the aminophylline micropellets (Euphyllin CR 350) resulted in the clinically desired concentration/time profile with highest theophylline plasma levels between 2:00 a.m. and 6:00 a.m., theophylline micropellets failed to do so. Apart from differences in the in-vitro release at low pH-values, this may be due to differences in solubility between aminophylline and theophylline, which become clinically relevant in the supine position at night.

Absorption↗
PubMed1983

Compliance testing by measurement of piracetam in urine--a possible method of compliance control for piracetam intakers. An empirical investigation.

All teams of investigators concerned with compliance rate have come to the conclusion that one can seldom rely on patients to take their tablets as prescribed. In case of long-term medication the problem becomes even more acute. A method for checking on compliance is, therefore, of great help in controlling medical therapy as well as in judging the effectiveness of pharmaceuticals. The results of this study imply that diachronic determination of piracetam concentration in patients' urine is an especially simple way of testing compliance without undue strain on the patient.

Adult↗
PubMed1981

E- and Z-10-hydroxylation of nortriptyline: relationship to polymorphic debrisoquine hydroxylation.

Eight healthy subjects [who were phenotyped with a debrisoquine (D) hydroxylation test] were selected to cover a wide range in the ratio between D and 4-hydroxydebrisoquine (4-OH-D) in the urine. After a single oral dose of nortriptyline (NT) the metabolic clearance by 10-hydroxylation in the E-position, but not in the Z-position, correlated closely to the metabolic ratio D/4-OH-D (rs = -0.88, p less than 0.01). This indicates that common enzymatic mechanisms are involved in the hydroxylation of D and the E- but not the Z-10-hydroxylation of NT. Slow hydroxylators of NT and D excreted less 10-hydroxynortriptyline in urine and had lower plasma clearance of NT than the rapid hydroxylators. The strong correlation (r = 0.96) between the total plasma clearance of NT and the metabolic clearance by E-10-hydroxylation shows that this metabolic reaction is important in the disposition of the drug.

Debrisoquin↗
PubMed1980

Pharmacogenetic covariation of defective N-oxidation of sparteine and 4-hydroxylation of debrisoquine.

Two subjects from each of the three groups of homozygous rapid, heterozygous, and homozygous non-metabolizers (N-oxidation) of sparteine received a single oral dose of debrisoquine. The urinary ratio of debrisoquine/4-hydroxy-debrisoquine, reflecting the individual's capacity to C-hydroxylate debrisoquine, was closely related to his phenotype for sparteine metabolism. This indicates that the two metabolic reactions are controlled by similar if not identical genetic factors.

Adult↗
PubMed1979

[Antiepileptic therapy with valproinic acid. Correlations of side effects and serum levels of valproinic acid].

The side effects and possible side effects of the therapy with valproic acid were documented in 66 outpatients with epilepsy over a period of one year. The serum levels of valproic acid were measured gaschromatographically over the same period. The majority of the patients received a combined medication. The occurrence of side effects or possible side effects of valproic acid led to a dosage reduction of discontinuation of the compound in 25% of the patients. Patients complaining of tiredness showed significantly higher serum valproic acid levels than patients without clinical side effects. The other comparisons between the serum valproic acid levels in the case of clinical side effects and changes in laboratory findings and the serum levels of patients without side effects or changes in laboratory findings did not indicate a definite difference.

Acne Vulgaris↗
PubMed1978

[Valproic acid in the treatment of epilepsy with special emphasis on serum level determination (author's transl)].

Valproic acid has become a regular component of antiepileptic therapy. Generally it is used against genetically caused, primary generalized epilepsies with bilateral hypersynchronous neuronal discharges in the EEG. An improvement can also be observed by Valproic acid-treatment for secondary generalized and partial epilepsies. Therapeutic results could possibly be improved through a consideration of the serum concentration of valproic acid. Some of the commercial preparations contain the sodium salt of Valproic acid. The free acid which is quickly absorbed, is released in the stomach (tablet) or in the intestine (dragee). The half life is about 15 to 17 hours (one finds a range of 6 to 20 hours in the literature). In view of the half life, it is recommended that the daily dose should be divided into three single doses. About 84 to 95% of the substance is protein bound. Up to now, clinically relevant observations concerning the displacement of valproic acid from its protein binding are unknown. Recently in in vitro studies a decreased protein binding of valproic acid due to phenylbutazone, salicylic acid, and sulfadimethoxine and vice versa, a displacement of phenobarbital and phenytoin caused by valproic acid could be demonstrated. The therapeutic range of the serum level was between 50 and 120 mcg/ml. Individual patients showed that the dispensed dose did not reliably yield the expected serum levels. The necessary daily dose lies for adults between 600 and 2400 mg, in children between 15 and 150 mg/kg. The wide range of allowable dosis is dependent on whether or not valproic acid is to be given in conjunction with other antiepileptic drugs. When phenobarbital and valproic acid are given in conjunction one should be alert for a rise in the phenobarbital serum level. Results of studies in which valproic acid was combined with several other antiepileptic and psychotropic drugs are reported. The majority of the researchers determine a clear parallelism between clinical improvement and a normalization of the EEG in primary generalized epilepsies with bilateral synchronous 3/sec. spikes and waves. The background activity, determined by visual inspection, is not affected. Few workers discuss the correlation of the side effects of valproic acid and its serum level. Tiredness and impaired function of thrombocytes has been observed to be dependent on the valproic acid plasma level.

Blood Platelets↗
PubMed1978

[Blood level courses after i.v., i.m. and p.o. administration of theophylline ethylendiamine and pH-neutral solution of theophylline (author's transl)].

Serum theophylline concentration was measured in nine patients with chronic-obstructive lung disease following oral, i.m. and i.v. application. Two different preparations were tested: A pH-neutral solution of theophylline (Solosin) and theophylline-ethylenediamine. 208 mg of the pH-neutral solution of theophylline showed very similar serum concentrations as did 240 mg i.v. or p.o., but definitely higher than in the case of 360 mg i.m. theophylline ethylenediamine. After 10 min following the oral or the intramuscular application, serum concentrations were high enough for strong bronchodilating action. The oral dosages only reached the lower limit of optimal concentration for the best bronchodilation. There is a decrease of the blood concentrations by 50% after about 5 h. The bronchodilating effect subsided 2-4 h after i.v. injection.

Administration, Oral↗