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Biomedical subjects

I Meineke

Publications and source records attributed to I Meineke.

46 records · Page 3Linked to original sources
PubMed1989

Transdermal delivery of mepindolol and propranolol in normal man. 2nd communication: pharmacokinetic and neuro-endocrine aspects.

The plasma and urinary pharmacokinetics of mepindolol and propranolol were assessed in nine healthy volunteers after single and 1-week daily repeated application of the drugs by a novel transdermal delivery system (BIO TSD). Qualitatively, the time courses of the plasma concentrations for both compounds were similar and indicative of effective drug input. On the first day of the treatment courses plasma levels rose slowly, reaching their observed maximum after 24 h. The latter still was in the rising phase of the curve and further input on longer application is likely. After 1 week daily repeated application apparent steady state conditions were reached. The plasma concentrations were low in comparison to the levels reported for oral dosing. Only small amounts of unchanged drug were excreted via urine. The effects of the investigational treatments on supine-resting and stimulated neuroendocrine variables were assessed also. A blunting of the adrenaline response to delayed auditory feed-back mental stress testing (DAF) was consistently observed after propranolol, but not after mepindolol. Noradrenaline responses to DAF were not altered. No consistent effects were observed in terms of the adrenaline responses to 3 min isometric handgrip testing (IHG). Noradrenaline responses to IHG were slightly blunted, relative to placebo on the first day when propranolol and mepindolol were applied. This was probably related to the usually high responses to placebo as reference. At the end of 1 week repeated application of the patches mean supine resting plasma renin activity (PRA) was significantly reduced by propranolol but not by mepindolol, and the mean PRA responses to 5 min i.v. infusion of isoprenaline was reduced by both.

Administration, Cutaneous↗
PubMed1989

Pharmacokinetic and pharmacodynamic interactions between single oral doses of ibopamine and food in normal man.

The pharmacokinetic and pharmacodynamic interactions between single oral doses of 200 mg ibopamine and a standard cold 3100 kJ meal were assessed in 12 normal male subjects, who were studied on 4 occasions, receiving either ibopamine or matched placebo (double-blind) in fasting condition or at the end of a meal. Treatments were randomly allocated in a period-balanced within-subject cross-over study design. The plasma concentrations of epinine (N-methyldopamine) were extensively profiled up to 4 h after dosing. Food caused a profound reduction of both Cmax and AUC of unconjugated epinine with a prolongation of Tmax. The subjects were furthermore profiled in detail up to 4 h after dosing by transthoracic impedance cardiography. Food caused substantial and protracted effects that affected virtually all parameters profiled. Ibopamine had clear cardiac performance enhancing effects only over the first hour after dosing. These effects were furthermore subject to significant food interaction. It therefore appeared that food resulted in a profound blunting of both ibopamine's pharmacokinetic and pharmacodynamic characteristics.

Administration, Oral↗
PubMed1987

Simultaneous determination of 5-aminosalicylic acid and 5-acetylaminosalicylic acid by high-performance liquid chromatography.

A high-performance liquid chromatographic method has been developed for the simultaneous determination of 5-aminosalicylic acid (5-ASA) and its main metabolite 5-acetylaminosalicylic acid (5-AcASA) in plasma, with 4-acetylaminosalicylic acid as an internal standard. Prior to extraction into ethyl acetate, 5-ASA is derivatized to 5-carbobenzyloxyaminosalicylic acid (5-CboASA). The calibration graphs for both 5-ASA and 5-CboASA are linear between 0.1 and 20.0 mumol/l. The limit of detection is 0.02 mumol/l for 5-ASA and 0.05 mumol/l for 5-AcASA. At 0.1 mumol/l, the coefficients of variation were 8.1 and 9.8% for 5-ASA and 5-AcASA, respectively. At 1.0 and 10.0 mumol/l, the coefficients of variation were 4.1% or less. The mean bias ranged from -6.2 to -2.0% for 5-ASA and from +6.0 to 0% for 5-AcASA.

Aminosalicylic Acids↗
PubMed1987

Postprandial changes in supine and erect heart rate, systemic blood pressure and plasma noradrenaline and renin activity in normal subjects.

The haemodynamic effects of a standard meal were assessed in a balanced cross-over study in eight normal fasting subjects, investigated under conditions applicable to many drug tests. Both the supine and erect diastolic blood pressure were reduced on average by 10 mmHg over the 4 h following the meal. The supine systolic pressure was increased on average by 2 mmHg, a difference of no biological relevance. Erect systolic blood pressure was not affected by eating. Supine heart rate was slightly but significantly increased, but the erect heart rate did not change. Postprandial plasma renin activity was increased. Venous plasma noradrenaline levels in the supine position were not affected by eating and after standing erect, and immobile for 5 min they were only slightly and not-significantly increased. A food-induced vasodepressor response combined with baroreceptor resetting is considered to have occurred in this population. The changes had a gradual onset, reaching their maximum about 2 h after eating and they were still evident after 3 h. Eating should be considered as an important potential source of bias in cardiovascular studies.

Adult↗
PubMed1987

A simple BASIC program for the calculation of nonparametric confidence intervals in bioequivalence testing.

A BASIC program is described which allows the calculation of confidence intervals on the basis of observations following a balanced two-way cross-over design. The algorithms executed by the program are completely outlined. They do not contain assumptions as to the expected properties of the sampling distribution. The function of the program modules is explained in detail with reference to the program listing provided. A test run of the program is presented, which demonstrates its validity on the basis of literature data.

Mathematical Computing↗
PubMed1986

Sensitive high-performance liquid chromatographic determination of pirenzepine in plasma.

A high-performance liquid chromatographic method for the determination of pirenzepine in human plasma is reported using imipramine as an internal standard. The assay has a lower limit of detection of 2.5 ng/ml. The calibration function is found to be linear in the range from 5 ng/ml up to at least 100 ng/ml. Two sets of chromatographic conditions are described, which provide different chromatographic selectivities for the separation of the compounds of interest from other material present in a sample.

Benzodiazepinones↗
PubMed1985

High-performance liquid chromatographic determination of cefonicid in human plasma and urine.

A high-performance liquid chromatographic assay for determination of cefonicid concentrations in human plasma and urine samples has been developed using cefazolin as an internal standard. For the analysis of plasma samples two calibration curves were utilized covering the cefonicid concentration ranges of 0.05-1.0 microgram/ml and 1.0-50.0 micrograms/ml, respectively. Coefficients of variation of 7.4% or less were obtained for cefonicid concentrations of 0.05-50.0 micrograms/ml. Mean bias was +6.0% at 0.05 micrograms/ml cefonicid and between -2.1% and +1.6% for 1.0-50.0 micrograms/ml cefonicid. Plasma samples containing 30 ng/ml cefonicid could be well distinguished from blank plasma samples. Urine samples were analysed by using a calibration curve for cefonicid concentrations between 1.0 and 50.0 micrograms/ml. ranged from 8.6% at a cefonicid concentration of 1.0 microgram/ml to 0.5% at 50.0 micrograms/ml with a mean bias between -3.0% and +0.3%.

Cefamandole↗
PubMedDate not supplied

Temelastine, a novel histamine H1-receptor antagonist, does not induce oxidative hepatic enzyme activity in man.

Temelastine (SK&F 93944) is a novel histamine H1-receptor antagonist with a high degree of protein binding and predominant hepatic elimination. The pharmacokinetics of antipyrine were assessed in eight male normal subjects after single oral doses of 10 mg/kg antipyrine, administered prior to chronic dosing with temelastine 100 mg twice daily for 2 weeks, and 48 hours after the last dose of temelastine. After the first dose of antipyrine the mean maximum plasma concentration (Cmax) was 78.3 mumol/l (range: 60.3 to 95.8), the mean AUC (0-infinity) was 1330 mumol.h/l (range: 1030 to 2074), the mean apparent terminal disposition rate constant K was 0.0656 h-1 (range: 0.0428 to 0.0769) and the mean residence time (MRT) was 16.7 h on average (range: 14.4 to 24.1). After the second dose the mean Cmax, AUC (0-infinity) and MRT had slightly increased by on average 11, 5 and 7% respectively whereas the mean K had decreased by 9%. None of the differences between the means of the log-transformed parameters for second-first dose reached statistical significance. Temelastine therefore did not appear to induce hepatic oxidative enzyme activity in man, as judged by antipyrine as a model substance.

Aged↗