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Biomedical subjects

G Leopold

Publications and source records attributed to G Leopold.

At least 19 recordsLinked to original sources
PubMed1992

Placebo controlled comparison of acute effects of ebastine and clemastine on performance and EEG.

The effects of single oral doses of 10 and 20 mg ebastine were compared with placebo and 2 mg clemastine in a double-blind cross-over study in 16 healthy male volunteers. Clemastine produced the known pattern of changes, namely impairment of psychomotor performance, drowsiness, and a selective effect on cognitive processes. Earlier encoding in a perceptual stage was slowed whereas abstract classification processes were not affected. Electrophysiological measures of vigilance showed a general decrease in vigilance especially 2.5 and 4.5 h after dosing. In contrast at no time was any effect of ebastine different from that of the placebo. Ebastine 10 and 20 mg differed positively from clemastine in its effect on pursuit tracking, subjective rating of drowsiness and general discomfort. Ebastine 10 mg also differed positively from clemastine in the EEG features of vigilance. It is concluded that 10 and 20 mg ebastine were free from sedative adverse effects.

Adult↗
PubMed1987

Pharmacokinetics of bisoprolol during repeated oral administration to healthy volunteers and patients with kidney or liver disease.

The pharmacokinetics of bisoprolol were investigated following oral administration of 10mg once daily for 7 days in 8 healthy subjects, in 14 patients with different degrees of renal impairment and in 18 patients with liver disease. In healthy subjects peak and trough steady-state concentrations of 52 micrograms/L and 11 micrograms/L, respectively, an elimination half-life of 10.0 hours and total body clearance of 14.2 L/h were observed. 5.21 mg/24 hours of unchanged bisoprolol were recovered following urinary excretion during the dosage interval. In 11 patients with renal impairment (mean CLCR = 28 +/- 5 ml/min/1.72m2) half-life was prolonged to 18.5 hours, and peak and trough concentrations were 74 and 32 micrograms/L, respectively. Correspondingly, urinary excretion decreased to 3.35 mg/24 hours and total body clearance to 7.8 L/h. In uraemic patients (CLCR less than 5 ml/min/1.73m2) the total clearance of bisoprolol was 5.0 L/h and the elimination half-life was 24.2 hours. In patients with liver cirrhosis half-life increased to 13.5 hours, steady-state peak and trough concentrations increased to 62 and 22 micrograms/L, respectively, and total body clearance decreased to 10.8 L/h. The present study indicates that in patients with impairment of kidney or liver function accumulation of bisoprolol above a factor of 2 did not occur. However, in the terminal stages of insufficiency of kidney or liver function bisoprolol dosage should not exceed 10mg.

Adrenergic beta-Antagonists↗
PubMed1987

Hydrops due to myocarditis in a fetus.

At 18 weeks of gestation a fetus was studied sonographically because of advanced maternal age and found to have hydrops of unknown etiology with ascites, pleural, and pericardial effusions. An abortion was performed and in the fetal/placental material myocarditis and thyroiditis were documented. Maternal antibodies to Coxsackie virus B5 showed a onefold rise. Tentatively, the hydrops is assigned to Coxsackie virus myocarditis, a lesion not previously identified in fetuses.

Adult↗
PubMed1986

Balanced pharmacokinetics and metabolism of bisoprolol.

Bisoprolol exhibits a high absolute bioavailability (90%) because of its nearly complete absorption (greater than 90%) and small first-pass effect (10%). Bioavailability is independent of food intake. A long plasma-elimination half-life (10-11h) allows a once-a-day dose regimen. Because of the low plasma protein-binding (30%), kinetics are insensitive to protein-binding interactions. The balanced clearance (equieffective hepatic and renal clearance) renders the kinetics virtually insensitive to renal or hepatic insufficiency. Even in the case of complete failure of one clearance organ, the plasma elimination half-life of bisoprolol would only double. The metabolites that are inactive and do not accumulate are eliminated predominantly by the kidneys. There is no stereoselective metabolism. The metabolism of bisoprolol is insensitive to liver enzyme inhibition (cimetidine), and nearly insensitive to liver enzyme induction (rifampicin). The metabolism is independent of genetic oxidation-polymorphism (debrisoquine). The pharmacokinetics of bisoprolol are independent of the dose in the range from 2.5 to 100 mg. There is no age or sex dependency. Bisoprolol exhibits predictable pharmacokinetics with well-balanced properties leading to small intra- and interindividual variability of the plasma concentration time curves and pharmacokinetic parameters. Bisoprolol is the beta-blocker with LADME(liberation, absorption, distribution, metabolism, and elimination)-optimized pharmacokinetics. This is a prerequisite for therapeutic reliability.

Administration, Oral↗
PubMed1986

Pharmacokinetics and metabolism of bisoprolol-14C in three animal species and in humans.

The pharmacokinetic properties of bisoprolol-14C were studied in Wistar rats, beagle dogs, and Cynomolgus monkeys. Bisoprolol is well absorbed in these species; independent of the route of administration (i.v. or p.o.), 70-90% of the 14C-dose was recovered in urine. Faecal excretion was approximately 20% in rats and less than 10% in dogs and monkeys. Rats excreted approximately 10% of the dose in bile after i.v. as well as after oral administration. The plasma half-life of the unchanged drug was approximately 1 h in rats, 3 h in monkeys, and 5 h in dogs. The bioavailability was 40-50% in monkeys, approximately 80% in dogs, and 10% in rats. Studies in rats have shown that the drug is rapidly taken up by the tissues. After i.v. administration, high levels of radioactivity were found in lung, kidneys, liver, adrenals, spleen, pancreas, and salivary glands. After oral administration, the highest concentration occurred in the liver and kidneys. With the exception of plasma and liver, unchanged bisoprolol was the major radioactive constituent in all tissues studied. Both the blood-brain and placental barriers were penetrated, but only to a small degree. No accumulation of radioactivity in tissues was observed after repeated dosing (1 mg/kg/day). The metabolism of bisoprolol was studied in the same three animal species and in humans. The major metabolites are the products of O-dealkylation and subsequent oxidation to the corresponding carboxylic acids. The amount of bisoprolol excreted unchanged in the urine is 50-60% of the dose in humans, 30-40% in dogs, and approximately 10% in rats and monkeys.

Absorption↗
PubMed1986

Concentration kinetics of propranolol, bisoprolol, and atenolol in humans assessed with chemical detection and a subtype-selective beta-adrenoceptor assay.

After oral administration of single doses of 240 mg of (+/-)propranolol (prop), 200 mg of (+/-)-atenolol (aten), and 100 mg of (+/-)-bisoprolol (biso) to six healthy male volunteers, the plasma concentration time profile was investigated. To measure total plasma concentrations of the parent racemic mixture of drug administered, a HPLC-assay of drug concentrations was used. To detect active metabolites and stereoselective pharmacokinetics of the racemates, plasma concentrations were also monitored by means of a subtype-selective receptor assay, using a beta 1-adrenoceptor preparation from rat salivary glands. It is shown that relevant amounts of active metabolites do not become apparent for either of the three drugs investigated. Furthermore, for neither of them can significant stereoselective elimination characteristics be seen. Monophasic elimination characteristics with t1/2 of 4.8 +/- 0.42 (prop), 6.87 +/- 0.46 (aten), and 9.19 +/- 0.38 h (biso) become apparent. The maximum concentrations observed after administration of the doses mentioned previously were 220 +/- 71 (prop), 904 +/- 104 (aten), and 445 +/- 32 (biso) (ng/ml plasma). One can conclude from comparison with the results from receptor-binding studies that the 100 mg dose of biso is five- to seven-fold more potent than the 200 mg dose of aten, with respect to antagonism versus beta 1-adrenoceptor-mediated effects.

Adrenergic beta-Antagonists↗
PubMed1986

Pharmacodynamic profile of bisoprolol, a new beta 1-selective adrenoceptor antagonist.

The pharmacodynamic profile of bisoprolol, a new beta 1-selective adrenoceptor antagonist, was investigated in four independent studies including 36 healthy male volunteers. Using the model of exercise-induced tachycardia (ET) the beta-adrenoceptor blocking properties of bisoprolol (2.5-40 mg) were examined in comparison to metoprolol (50 and 100 mg), propranolol (40 and 80 mg) and atenolol (50 and 100 mg). The maximal reduction of ET was achieved between 1 and 4 h following single oral administration. The dose-response relationship using individual maximal reduction of ET showed, on a molar basis, that bisoprolol is about 5, 7 and 10 times more effective than propranolol, atenolol and metoprolol, respectively. In the model of insulin-induced hypoglycaemia bisoprolol behaved as a beta 1-selective adrenoceptor antagonist. There was a good correlation (r = 0.94) between the log bisoprolol concentration and the reduction in exercise-induced tachycardia. Bisoprolol is a potent new cardioselective beta-adrenoceptor antagonist with a competitive action at beta 1-adrenoceptors.

Adrenergic beta-Antagonists↗
PubMed1980

Diagnosis of a triploid fetus at genetic amniocentesis.

Nearly 20% of spontaneously aborted fetuses with chromosomal errors have been shown to have a triploid karyotype. Such a fetus is rarely encountered during the course of an amniocentesis at midtrimester. Because amniotic fluid cell polyploidy is an occasional finding among normal fetuses at midtrimester, the following report illustrates the importance of gathering corroborative evidence of an affected fetus before arriving at a prenatal diagnosis.

Adult↗
PubMed1980

Diagnosis and follow-up of intraventricular and intracerebral hemorrhages by ultrasound studies of infant's brain through the fontanelles and sutures.

A technique to diagnose subependymal hemorrhage (SEH), intraventricular hemorrhage (IVH), intracerebral hemorrhage, and posthemorrhage hydrocephalus in tiny infants, using real time ultrasound studies of the brain ventricular system, is described. This is a bedside technique that visualizes the brain through the fontanelles and the sutures, in three planes: coronal, sagittal, and horizontal. Excellent visualization of the ventricular system, caudate nuclei, the thalamus, the choroid plexus, the corpus callosum, and the foramen of Monro is obtained. This method has good definition using high frequency transducers since there is no bone interference. The ultrasound diagnosis correlated well with computed tomography (CT) and with direct pathologic studies. This technique was more sensitive in diagnosing small IVH/SEH and organized clots than were CT studies. IVH/SEH were found in 90% of 113 infants less than or equal to 34 weeks of gestation; 49% of the hemorrhages were large and 41% were small. Most hemorrhages were found in the first scan, usually shortly after birth. Twenty-one premature infants who never had perinatal asphyxia or respiratory distress syndrome had IVH/SEH. The hemorrhages were followed until disappearance, usually in one to three months in cases of large hemorrhages.

Cerebral Hemorrhage↗
PubMed1979

Cephalothoracopagus (Janiceps) twinning.

Conjoined twins occur with a frequency of 1/50,000--1/100,000 deliveries. The cephalothoracopagus variety is particularly rare. This paper presents a case report of cephalothoracopagus (Janiceps) twinning, with a detailed pathologic analysis, as well as an historical review and discussion of diagnostic modalities.

Adult↗
PubMed1979

Clinical pharmacology phase I of cefazedone, a new cephalosporin, in healthy volunteers. II. Pharmacokinetics in comparison with cefazolin.

In two consecutive cross-over studies, each involving 10 healthy volunteers, the pharmacokinetics of (6R,7R)-7-(2-[3,5-dichloro-4-oxo-1(4H)-pyridyl]-acetamindo)-3-([(5-methyl-1,3,4-thiadiazol-2-yl)-thio]methyl)-8-oxo-5-thia-1-azabicyclo[4,2,0]oct-2-ene-2-carboxylic acid (cefazedone, Refosporen) in comparison with cefazolin were investigated after single i.v. and i.m. administration. The doses were: i.v. cefazedone 500 mg and 1000 mg; cefazolin 1000 mg; i.m. cefazedone 500 mg, cefazolin 500 mg. The pharmacokinetic parameters were analysed by applying an open two-compartment model. The pharmacokinetics of cefazedone are nearly identical with those of cefazolin. In particular, it must be noted that cefazedone has a relatively long serum elimination half-life (1.64 +/- 0.23 h after i.v. and 1.85 +/- 0.51 h after i.m. administration) and that cefazedone exhibits, in comparison with cefazolin, a more favourable concentration ratio of central vs. peripheral (= tissue) compartment (1:2).

Adult↗
PubMed1978

Clinical pharmacology in normal volunteers of praziquantel, a new drug against schistosomes and cestodes. An example of a complex study covering both tolerance and pharmacokinetics.

The tolerance of Praziquantel (2-cyclohexylcarbonyl-1, 3, 4, 6, 7, 11b-hexahydro-2H-pyrazino-[2, 1-a]isoquinoline-4-one) in oral doses of 1 X 20 mg/kg, 1 X 50 mg/kg, 3 X 10 mg/kg and 3 X 25 mg/kg body weight (tau = 4 h) was tested in a complex study involving 36 healthy volunteers. In addition to the usual assessment of clinical chemistry, haematology, coagulation physiology, urinalysis, clinico-physiological examination including EEG, and medical examination, clinico-psychological parameters were also recorded and special neurological investigations were performed. No clinically relevant changes were found in any of the laboratory parameters, nor in the medical-neurological or clinico-physiological examinations. Based on a few clinico-psychological parameters and subjective comments, the largest daily dose tested (3 X 25 mg/kg = 75 mg/kg) produced a slight, transient disturbance in general well-being, which was barely detectable on objective clinical examination. The pharmacokinetic behaviour was dominated by rapid metabolism and pronounced first-pass metabolism of praziquantel, which greatly limits the value of results obtained by GC analysis of unchanged drug in serum. The peak concentration in serum was reached after 1--2 h, and the elimination half-life for the period 2--8 h was 1--1.5 h.

Adult↗
PubMed1978

Comparative bioavailability: influence of various diets on the bioavailability of indomethacin.

After oral application of 100 mg indomethacin to eight healthy male volunteers, the concentrations in plasma and their time course were determined when the drug was given to fasting individuals or after a high-protein, a high-lipid or a high-carbohydrate meal. The study was designed as a fourfold-crossover experiement with intermissions of at least one week between applications. Indomethacin in plasma was determined by fluorimetry after a double extraction procedure. Indomethacin plasma concentrations and the truncated areas under the curves (AUC) were evaluated. Administration to fasting subjects provides higher plasma levels and a smaller tmax value than after either one of the three diets. Also the absorption rate was higher in fasting individuals. However, the absorbed amount of indomethacin after 24 hr was practically equal in all four groups. Attempts to distinguish between the effects of the various diets revealed significant differences in the time period necessary to reach the peak values. After high-protein and high-lipid diets they were reached in the 90 min sample while after high-carbohydrate 120 min were required. These values are significantly different from fasting controls (45 min) and from each other. There is no great influence of food on the other aspect of bioavailability, amount of unchanged drug reaching the systemic circulation.

Adult↗