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Biomedical subjects

C De Mey

Publications and source records attributed to C De Mey.

At least 19 recordsLinked to original sources
PubMed1997

Evaluation of the noninvasive estimates of cardiac output by Doppler aortoechography according to test-theoretical principles.

The usability of noninvasive methods can be quantified by a formal assessment of empirical quality criteria based on test-theoretical principles. The ACVF Doppler aortoechography is a pulsed dual-beam ultrasound technique with online estimates of cardiac output (CO) based upon the measurement of the mean Doppler shift frequency across the ascending aorta, its estimated cross-sectional area and the cycle's heart rate. The method has a relatively high reliability, sensitivity, and pharmacosensitivity (for inodilatory changes in particular), but tends to underestimate cardiac output. Furthermore, the method lacks objectivity because it is highly observer-dependent. Precise method description and stringent standardization thus are required. Because of the method specificity of its estimates, data should not be combined with those of other methods. The inherently poor validity of its CO estimates, using this method, call for caution in the mechanistic interpretation of its observations.

Adult↗
PubMed1997

Hemodynamic surrogate end-points in phase I studies?

Clinical pharmacology studies in healthy volunteers ("human pharmacology studies") characterize the pharmacokinetic and pharmacodynamic hallmarks of pharmacological action and their interrelation in the intact effector system unconfounded by disease and comedication. They constitute a valuable basis for the subsequent explicit investigation of the clinical efficacy, safety, efficiency, and therapeutic benefit in patients, but are not a valid surrogate for them.

Clinical Trials, Phase I as Topic↗
PubMed1997

Inverse PK/PD: estimation and differentiation of bioavailability from effect kinetics--observations with beta-adrenoceptor antagonists.

The time course of pharmacodynamic effects allow to resolve bioavailability relevant pharmacokinetic information, provided simple assumptions can be made about their interrelation. This approach furthermore allows to differentiate ancillary properties of chemically distinct pharmacological agents on the basis of their mutual pharmacodynamic actions. The advantages and pitfalls of this strategy are discussed here for beta-adrenoceptor antagonists on the basis of their pharmacodynamic characterization by the extent of their binding ability to ex vivo in vitro beta-adrenoceptors (RRA assay) and their blunting effects on the ergometric rise in heart rate.

Adrenergic beta-Antagonists↗
PubMed1996

Pantoprazole lacks interaction with antipyrine in man, either by inhibition or induction.

Substituted benzimidazole inhibitors of the gastric H+/K(+)-ATPase may interact with the cytochrome P450 enzyme system and alter the pharmacokinetics of coadministered drugs, as known for omeprazole. The primary aim of the present studies was to determine whether pantoprazole, a new, selective proton pump inhibitor, modifies the plasma concentrations of orally-administered antipyrine, a commonly used marker for mixed hepatic oxidase enzyme activity. In the acute study, 12 healthy male volunteers were given a) a single 30 mg i.v. doses of pantoprazole, b) a single 5 mg/kg oral dose of antipyrine, or c) coadministered pantoprazole and antipyrine according to a randomized three-period change-over design. In the chronic study, another 12 volunteers received 40 mg once-daily oral doses of pantoprazole on day 3 and on days 5-12, and a single oral 5 mg/kg dose of antipyrine on days 1, 12 and 14. Antipyrine plasma concentrations were measured without pantoprazole (day 1), on the last day of chronic dosing with pantoprazole (day 12) and 48 hours after the last dose of pantoprazole (day 14) to differentiate between inhibition and induction, respectively. Both drugs were well tolerated and no adverse events or clinically relevant alterations in vital signs or laboratory parameters were observed during treatment. The point estimates of the respective AUC-and Cmax-ratios for antipyrine with and without pantoprazole were 0.99 and 0.98 in the acute study, and 1.01 and 0.93 on day 12, and 1.04 and 0.99 on day 14 of the chronic study. The corresponding 90%-confidence intervals were all within the equivalence range of 0.8-1.25 so that lack of interaction either by inhibition or induction can be concluded.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1996

Differentiation of inodilatory responses by non-invasive measures of cardiovascular performance in healthy man.

The cardiovascular responses to various inodilatory interventions were investigated noninvasively in healthy man by monitoring heart rate (HR), blood pressure (SBP/DBP, according to Korotkoff I and IV criteria), systolic time intervals (PEP, VET and QS2) and impedance cardiographic estimates of stroke volume (SV) and cardiac output (CO). The following inodilatory interventions were evaluated and compared: the i.v. infusion of adrenaline (1 microgram/min), the i.v. infusion of isoprenaline (1 microgram/min) with and without pretreatment with 100 mg talinolol (a beta 1-selective beta-adrenoceptor antagonist), the p.o. administration of 1200 mg celiprolol (a beta 1-adrenoceptor antagonist with ancillary beta-adrenergic agonistic properties at the chosen dose level), the p.o. administration of 0.4 mg bimakalim (a K+ channel activator without direct cardiac effect) with and without pretreatment with 5 mg bisoprolol and the p.o. administration of the PDE-III inhibitors meribendan and isomazole. The extent of the inodilatory rise of HR, shortening of PEP, rise of SV and CO relative to the associated reduction of the calculated total peripheral resistance (TPR) proved a powerful tool to differentiate inodilatory properties: adrenaline, isoprenaline after beta 1-selective beta-adrenoceptor blockade and celiprolol led to similar ancillary adrenaline-like cardiovascular changes relative to the vasodilatation; bimakalim led to similar associated changes except for a relatively larger rise in HR, which could be blocked by bisoprolol; isoprenaline induced clearly larger associated changes, for which HR, VET, and QS2c were particularly sensitive; meribendan and isomazole resulted in the largest ancillary changes, characterized by a critical shortening of the ejection time VET, so that the rise of CO was almost exclusively defined by the rise of HR. These differences could be detected and differentiated sufficiently and adequately by HR, SV, CO, TPR, PEP, and VET. There seems little value in using more assumptive variables such as HR-corrected VETc and QS2c, the Weissler index and the impedance cardiographic Heather index.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1995

Method specificity of the auscultatory estimates of the inodilatory reduction of diastolic blood pressure based on Korotkoff IV and V criteria.

1. Non-invasive measurements of blood pressure (BP) are method-specific estimates of actual blood pressure. The agreement of the auscultatory Korokoff V ('disappearance' of sound, kv) and Korokoff IV ('sound muffling' kiv) cut-off points in measuring diastolic blood pressure (DBP) was evaluated in healthy subjects in the presence of various controlled inodilatory interventions. 2. Eating (n = 8), 10 min i.v. infusion of 1 microgram min-1 isoprenaline and adrenaline (n = 12), p.o. administration of 40 mg of the PDE-III inhibitors isomazole and meribendan (n = 18) and p.o. administration of 1200 mg celiprolol (n = 15) caused evident chrono-inodilatory responses: average HR increases of 7, 19, 10, 17, 17 and 8 beats min-1, estimated CO increases of 1.6, 4.5, 2.3, 1.9, 2.6 and 1.8 1 min-1 and average shortening of QS2c of 18, 41, 8, 37, 42 and 9 ms for food, isoprenaline, adrenaline, isomazole, meribendan and celiprolol, respectively. 3. In general, there was good agreement between DBPkV and DBPkIV measurements before the administration of the inodilatory treatments (bias DBPkV-DBPkIV: 1-2 mm Hg) but the extent of inodilatory DBP reduction (-8, -6, -10, -2, -7 and -8 mm Hg according to DBPkIV for food, isoprenaline, adrenaline, isomazole, meribendan and celiprolol, respectively) was substantially overestimated when based on Korotkoff-V rather than -IV (bias DBPkV-DBPkIV in estimating the inodilatory effect on DBP: -8, -12, 1, -13, -12 and -7 mm Hg for food, isoprenaline, adrenaline, isomazole, meribendan and celiprolol, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1995

Method specificity of non-invasive blood pressure measurement: oscillometry and finger pulse pressure vs acoustic methods.

1. The agreement of blood pressure measurements by stethoscope auscultation (SBPa, DBPa-IV and DBPa-V), oscillometry (Dinamap; SBPo, and DBPo) and digital photoplethysmography (Finapres; SBPf, and DBPf) with the graphical analysis of the analogue microphone signals of vascular wall motion sound (SBPg and DBPg) was evaluated in eight healthy subjects in the presence of responses to the intravenous infusion of 1 microgram min-1 isoprenaline. 2. In general, there was good agreement between the SBP/DBP-measurements based on auscultatory Korotkoff-I- and IV-criteria and the reference method; the average method difference in estimating the isoprenaline responses for SBPa-SBPg was: -1.1, 95% CI: -5.4 to 3.1 mm Hg with a within-subject between-method repeatability coefficient (REP) of 11.6 mm Hg and for DBPa-IV-DBPg: 3.5, 95% CI: -0.5 to 6.5 mm Hg, REP: 11.5 mm Hg. The ausculatation of Korotkoff-V substantially overestimated the isoprenaline induced reduction of DBP: method difference DBPa-V-DBPg: -11.3, 95% CI: -17.8 to -4.7 mm Hg, REP: 31.8 mm Hg. 3. Oscillometry yielded good approximations for the SBP response to isoprenaline (average method difference SBPo-SBPg: -2.9, 95% CI: -9.0 to 3.3 mm Hg, REP: 17.6 mm Hg) but was poorly sensitive with regard to the DBP responses: method difference DBPo-DBPg: 6.5, 95% CI: -1.3 to 14.3 mm Hg, REP: 25.7 mm Hg. 4. Whilst the finger pulse pressure agreed well with regard to DBP (method difference for the DBP responses to isoprenaline: DBPf-DBPg: 1.8, 95% CI: -5.1 to 8.6 mm Hg, REP: 18.5 mm Hg) it was rather unsatisfactory with regard to SBP (method difference SBPf-SBPg: -14.1, 95% CI: -28.2 to -0.1 mm Hg, REP: 49.9 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1994

Reproducibility and consistency of the responses to supine bicycle ergometry; evaluation in conjunction with beta 1-adrenoceptor occupancies.

A protocol is presented for supine bicycle ergometry in healthy subjects, which aims for a target increase of heart rate (HR = 140 beats min-1) after 4 min cycling under constant load. The required load is selected from a pre-study ergometry with stepwise increasing load. Repeated testing with this protocol was shown to yield highly reproducible ergometric HR-responses. Because of their high reliability, the ergometric endpoints and increments permit a highly sensitive comparison of beta 1-adrenoceptor antagonism across dose and time within a given compound. The relationship between the changes of the ergometric rise of HR and the beta 1-adrenoceptor occupancy (estimated from radioreceptor assay data) permits to evaluate the ergometric efficiency of different beta-adrenoceptor antagonists across time and doses and to identify eventual differences that do not relate primarily to the extent of beta 1-adrenoceptor antagonism itself.

Adolescent↗
PubMed1994

Pantoprazole lacks interaction with antipyrine in man, either by inhibition or induction.

Substituted benzimidazole inhibitors of the gastric H+/K(+)-ATPase may interact with the cytochrome P450 enzyme system and alter the pharmacokinetics of coadministered drugs, as known for omeprazole. The primary aim of the present studies was to determine whether pantoprazole, a new, selective proton pump inhibitor, modifies the plasma concentrations of orally-administered antipyrine, a commonly used marker for mixed hepatic oxidase enzyme activity. In the acute study, 12 healthy male volunteers were given a) a single 30 mg i.v. doses of pantoprazole, b) a single 5 mg/kg oral dose of antipyrine, or c) coadministered pantoprazole and antipyrine according to a randomized three-period change-over design. In the chronic study, another 12 volunteers received 40 mg once-daily oral doses of pantoprazole on day 3 and on days 5-12, and a single oral 5 mg/kg dose of antipyrine on days 1, 12 and 14. Antipyrine plasma concentrations were measured without pantoprazole (day 1), on the last day of chronic dosing with pantoprazole (day 12) and 48 hours after the last dose of pantoprazole (day 14) to differentiate between inhibition and induction, respectively. Both drugs were well tolerated and no adverse events or clinically relevant alterations in vital signs or laboratory parameters were observed during treatment. The point estimates of the respective AUC- and Cmax-ratios for antipyrine with and without pantoprazole were 0.99 and 0.98 in the acute study, and 1.01 and 0.93 on day 12, and 1.04 and 0.99 on day 14 of the chronic study.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1993

Disagreement between standard transthoracic impedance cardiography and the automated transthoracic electrical bioimpedance method in estimating the cardiovascular responses to phenylephrine and isoprenaline in healthy man.

1. Impedance cardiography is a well-established noninvasive method to assess within-subject changes of cardiovascular function. We compared the standard approach (ZCG) which requires tedious signal analysis with an automated approach (TEB: NCCOM 3) with its own specific equipment, algorithms and equations in order to assess agreement of the method-specific measurements and calculations. 2. Ten healthy men were studied on two occasions with either ZCG or TEB, at rest and at the end of 5 min i.v.-infusions with 1 microgram min-1 isoprenaline and 100 micrograms min-1 phenylephrine. 3. There was good agreement for the method-independent changes (HR, SBP/DBP), but there were large differences for method-specific measurements: dZ/dtmax [TEB-ZCG] = -0.68, CI: -0.83 to -0.53 ohm s-1, PEP [TEB-ZCG] = -22.1, CI: -35.0 to -9.2 ms and QS2c [TEB-ZCG] = -16.5, CI: -32.4 to -0.6 ms and for the calculated stroke volume SV [TEB-ZCG] = 30.3, CI: 15.5 to 45.2 ml. The responses of dZ/dtmax and SV to isoprenaline and phenylephrine, although qualitatively similar, reached no quantitative agreement either. A substantial disagreement was evident for the STI responses to isoprenaline where TEB failed to detect the expected reduction of VETc and thus grossly underestimated the shortening of QS2c. 4. It is concluded that TEB-measurements and -calculations did not agree with standard ZCG, that the methods, albeit related, cannot be considered as interchangeable and that suspicion is justified that TEB might yield erroneous results under specific circumstances.

Adult↗
PubMed1993

Evaluation of the 13CO2 kinetics in humans after oral application of sodium bicarbonate as a model for breath testing.

The kinetics of 13CO2 have been investigated following oral administration at five doses between 12.5 and 100 mg of 13C labelled sodium bicarbonate to 10 healthy subjects in a randomized study. Sodium bicarbonate in this study served as a model compound for carbon dioxide/bicarbonate generated in breath tests. Exhalation of 13CO2 into breath was monitored by stable isotope ratio mass spectrometry. The kinetics of 13CO2 were characterized by an apparent terminal elimination half-life of 1 h and a mean recovery of 0.630 of the dose administered. The kinetics were not dose-dependent. These results were in agreement with the findings reported previously after i.v. application of sodium bicarbonate.

Administration, Oral↗
PubMed1992

Prandial and diurnal effects on the absorption of orally administered enteric coated 5-aminosalicylic acid (5-ASA).

Plasma and urine concentrations of 5-ASA and its N-acetyl metabolite 5-AcASA were measured over 48 h in 12 young healthy male subjects, who received three doses of three times enteric coated 500 mg 5-ASA tablets at 7 h interval, on two occasions 14 days apart. On one occasion the doses were given after standard meals; on the other occasion, they were given 1 h before meals. Administration of the tablets after meals delayed systemic drug absorption but did not affect the extent of absorption. There was a sharp rise in the plasma concentrations of 5-ASA and 5-AcASA in the early morning (i.e. circa 24 h after administration of the 1st dose) independent of when the tablets were taken with respect to the meals. This suggests that tablets or tablet fragments remained in the stomach until the later part of the night. Thus, diurnal effects may be more important than prandial effects in the evaluation of the kinetics of 5-ASA and its metabolites after peroral administration of enteric coated tablets.

Administration, Oral↗
PubMed1990

Carvedilol increases the systemic bioavailability of oral digoxin.

The effects of a single oral dose of 25 mg carvedilol on the plasma and urinary kinetics of digoxin after an oral and intravenous 0.5 mg dose, were investigated in two separate double-blind, placebo-controlled, period-balanced cross-over studies in healthy male subjects. Carvedilol increased the mean maximum plasma concentration and the area under the plasma concentration time-curve of digoxin when administered orally. The effects were virtually confined to the first 4 h after dosing, and the apparent terminal disposition rate constant was not changed. Carvedilol did not alter the plasma and urinary kinetics of intravenously administered digoxin.

Administration, Oral↗
PubMed1989

Routine measurement of plasma catecholamines in clinical pharmacology by high-performance liquid chromatography with electrochemical detection.

A method for the simultaneous determination of epinephrine, norepinephrine and dopamine in human plasma is described, which combines the advantages of liquid-liquid extraction sample preparation, high-performance liquid chromatography on weak cation-exchange stationary phases and dual-electrode coulometric detection. The limits of quantification are less than 5 pg/ml (at a signal-to-noise ratio greater than 5) for each analyte. The influence of various experimental parameters (e.g., composition of the mobile phase, pretreatment of the assay buffer, components of the re-extraction system) on the performance of the assay is reported in detail. A number of applications are presented, which demonstrate the quality of the data obtained in terms of sensitivity, reproducibility and significance.

Catecholamines↗