Biomedical subjects

M Grind

Publications and source records attributed to M Grind.

10 recordsLinked to original sources

PubMed1997

Bioequivalence, pharmacokinetic and pharmacodynamic response to combined extended release formulations of felodipine and metoprolol in healthy volunteers.

OBJECTIVE: The primary aim of this study was to investigate whether bioequivalence is achieved for a new fixed combination of extended-release (ER) felodipine and controlled-release (CR/ZOK) metoprolol compared with the free combination of felodipine ER metoprolol CR/ZOK. The second aim was to study whether there was an interaction in pharmacokinetics and pharmacodynamics between felodipine and metoprolol when administered as ER formulation. METHODS: Two four-way cross-over studies were performed in 36 young subjects and 24 elderly subjects with frequent measurement of drug plasma concentrations, blood pressures and heart rate. The pharmacokinetic analysis included enantioselective analysis in six subjects. RESULTS: Bioequivalence between the fixed combination and the free combination was observed for the two drugs (mean difference 27%) except for a minor deviation regarding Cmax of metoprolol in the elderly. No significant interaction was shown except for a small increase (6%) of metoprolol AUC in the younger subjects. Mean plasma S-/R-enantiomer ratios were almost identical for the different treatments. Blood pressure and heart rate was significantly reduced for the fixed combination compared with felodipine ER in the younger and the elderly subjects. No significant difference regarding pharmacodynamics was detected between the fixed combination and the corresponding free combination. CONCLUSION: The fixed combination consistently provides fairly constant and effective felodipine and metoprolol concentrations after once-daily administration of one tablet. It is clinically interchangeable with the free combination of metoprolol CR/ZOK tablets and felodipine ER tablets. Finally, felodipine and metoprolol do not interact on a pharmacokinetic level when administered as the fixed combination.

Adrenergic beta-Antagonists↗

PubMed1993

Method for studying drug-warfarin interactions.

The potential effects of extended-release felodipine on the pharmacokinetics and pharmacodynamics of warfarin were studied in a double-blind crossover study in 12 healthy men. Warfarin dosage was adjusted to achieve stable subtherapeutic anticoagulation. Subjects were then randomized to receive 2 weeks of treatment with 10 mg extended-release felodipine or placebo once daily, and warfarin dosage was adjusted if necessary to maintain stable international normalized ratio. The pharmacokinetics of R- and S-warfarin and the warfarin dose requirement did not differ importantly between periods of treatment with felodipine and placebo. The design of this study is suitable for general use in the identification of possible effects of other drugs on the pharmacokinetics and pharmacodynamics of warfarin. A different approach is needed if there is any reason to expect that warfarin may alter the pharmacokinetics or pharmacodynamics of the test drug.

Adult↗

PubMed1990

Drug interaction studies with remoxipride.

The interaction potential of remoxipride was investigated with biperiden, warfarin, diazepam, and ethanol. The studies were conducted in 12 healthy volunteers each of whom received single doses of remoxipride, the interacting drug, and the combination in a randomized crossover design. Remoxipride and biperidene had no influence on each other's pharmacokinetics. The pharmacokinetics of warfarin enantiomers were uninfluenced by remoxipride. Ethanol and diazepam had no effect on the pharmacokinetics of remoxipride. The effect of remoxipride on the elevation of plasma prolactin levels was not modified by biperiden and the effect of warfarin on the prolongation of prothrombin time was uninfluened by remoxipride. Remoxipride showed no pharmacokinetic interaction with any of the drugs studied, nor was any pharmacodynamic interaction observed in the remoxipride versus biperiden and remoxipride versus warfarin studies.

Adolescent↗

PubMed1989

Remoxipride--a new potential antipsychotic compound. Tolerability and pharmacokinetics after single oral and intravenous administration in healthy male volunteers.

The tolerability and pharmacokinetics of remoxipride were studied in 18 healthy normal male volunteers. Increasing oral doses of 0.5-100 mg were given to eight male volunteers in one study (study I). In addition, an intravenous (IV) infusion of 20 mg remoxipride and a 20 mg oral dose were given in an open crossover study to ten males (study II). Remoxipride was well tolerated with respect to cardiovascular effects, clinical chemistry, body temperature and adverse effects in all subjects. Following IV administration, remoxipride plasma concentrations declined exponentially in five subjects and biexponentially in the remaining five. The mean apparent volume of distribution was 0.5 l/kg (SD = 0.10) and the mean half-life 4.1 h (range 2.6-6.6). The recovery of unchanged remoxipride in urine was 10-36%, and the mean renal clearance was 32 ml/min (SD = 13). Remoxipride was a low clearance drug with a total plasma clearance of about 120 ml/min (SD = 41). The mean oral bioavailability was 96%. There was a linear relationship between the peak plasma concentration as well as the area under the concentration versus time curve and the administered dose. A transient increase in plasma prolactin concentrations occurred but there were no effects on plasma growth hormone levels.

Administration, Oral↗

PubMed1988

Remoxipride--a new potential antipsychotic drug. Pharmacological effects and pharmacokinetics following repeated oral administration in male volunteers.

Remoxipride, a new potential antipsychotic drug, was administered over 4 days at two dose levels, 70 and 140 mg t.i.d., to eight healthy male volunteers. Pharmacokinetics, safety, tolerability, and effect on plasma prolactin levels were evaluated. Remoxipride exhibited essentially linear pharmacokinetics. Only minor deviations in biochemical and physiological safety parameters were found. The drug was well tolerated by all subjects at the 70 mg dose level. At 140 mg akathisia appeared in seven subjects. The drug induced a rapid and transient increase in plasma prolactin concentrations at both dose levels after single doses. During steady state, a significant reduction in the prolactin response was observed as compared to after the first dose.

Administration, Oral↗

PubMed1987

Clinical pharmacokinetics of some newer diuretics.

Several new diuretics have recently been developed. This review summarises the published knowledge about some of them. Azosemide is a loop diuretic. The bioavailability is about 15% and it has a half-life of 2 to 3 hours. Renal and non-renal clearance are 1.32 and 5.4 L/h, respectively. Etozolin is also a loop diuretic. It is rapidly metabolised to the active metabolite, ozolinone. The gastrointestinal uptake of etozolin is almost complete. The plasma half-life of etozolin and ozolinone are 2 and 10 hours, respectively. The compounds are mainly eliminated as metabolites. Renal and liver impairment do not seem to change the pharmacokinetics. Fenquizone has properties similar to the thiazides. The plasma half-life is approximately 17 hours. Apparent volume of distribution averaged 686 L and renal clearance is 7.2 L/h. Indapamide acts predominantly on the proximal segment of the distal tubule and also has direct vasodilatory effects. Gastrointestinal uptake is at least 80%. The drug binds highly to carbonic anhydrases of red blood cells. Protein binding is about 80%, while terminal plasma half-life is 15 hours and the apparent volume of distribution 25 L. Renal clearance is 0.3 L/h and non-renal clearance 0.9 L/h. Several metabolites have been described, of which one major metabolite is pharmacologically active. Muzolimine is a loop diuretic. Its uptake is almost complete, but decreased substantially by food. The protein binding is about 65%, the apparent volume of distribution is about 1 L/kg and average terminal half-life 10 to 20 hours. Elimination is mainly non-renal, and non-renal clearance ranges between 0.5 and 1.32 L/h. The pharmacokinetics of the drug do not seem to be changed in cardiac failure. Terminal plasma half-life is essentially unchanged in patients with renal failure, except in those with very severe reduction of glomerular filtration rate. Piretanide is a loop diuretic which is about 6 times as potent as frusemide (furosemide). Its bioavailability is most likely complete in healthy subjects and in renal patients. Protein binding in healthy subjects is about 95%. The plasma half-life of the drug is about 1 hour and apparent volume of distribution averages about 17 L. Renal and non-renal clearance are about 6 L/h, although renal clearance is decreased in renal failure: this decrease is correlated with glomerular filtration rate. Non-renal clearance is unchanged in renal failure, as is the apparent volume of distribution.(ABSTRACT TRUNCATED AT 400 WORDS)

Diuretics↗

PubMed1986

Tolerance and pilot pharmacokinetics of amiflamine after increasing single oral doses in healthy subjects.

Oral doses of 1 to 100 mg amiflamine, a new reversible monoamine oxidase type A-selective inhibitor, were given for the first time in humans to six healthy men. No apparent pharmacologic effects were recorded until the 80 mg dose. After 100 mg, one subject developed symptoms indicative of an overdose. Amiflamine is extensively metabolized by two consecutive N-demethylations. The biotransformation patterns in plasma and urine were found to correlate with the debrisoquin metabolic ratio.

Adult↗

PubMed1986

Pressor response of oral tyramine in healthy men given amiflamine and placebo.

During two baseline challenge tests, oral tyramine (50 to 400 mg) was given to 12 healthy men to find each individual's cardiovascular pressor response. All 12 subjects "tolerated" 200 mg oral tyramine, but three of the 12 developed an increment in systolic blood pressure greater than 30 mm Hg when given a dose of 400 mg. Thereafter, amiflamine, 5 mg bid (n = 8), or placebo, 1 capsule twice a day (n = 4), were given in a double-blind fashion for 7 days, and oral tyramine challenge tests (12.5 to 400 mg) were given on days 5 to 7. During dosing with amiflamine or placebo, no subject tolerated 400 mg oral tyramine and no difference between the two regimens was found with regard to tyramine response. Plasma concentrations of amiflamine and two of its metabolites were measured on days 4 to 7. Steady-state concentrations were reached within 4 to 5 days. Plasma concentrations of tyramine after 400 mg tyramine showed a positive correlation with the increase in systolic blood pressure (P less than 0.001).

Administration, Oral↗

PubMed1986

Pharmacokinetics of zimeldine in male alcoholics.

The pharmacokinetics of zimeldine, a 5-HT reuptake blocker with antidepressive effects, was studied after a single oral dose and after multiple oral administration in 19 alcoholic males, 10 with and 9 without chronic liver damage. The average plasma concentration of zimeldine as assessed by the AUC values (area under the plasma concentration-time curve) was significantly higher in the chronically liver damaged patients than in the patients without chronic liver damage. The plasma half-life of zimeldine was also significantly longer in the chronically liver damaged patients. There were no differences in the obtained pharmacokinetic parameters between the patients having nonchronic liver damage and healthy control subjects. The pharmacokinetics of the active metabolite norzimeldine (resulting from N-demethylation of zimeldine) showed no differences between the two groups of alcoholics and the healthy controls. The IgA values were significantly correlated to both the AUC and plasma half-life of zimeldine. No other correlation between clinical chemistry parameters and pharmacokinetic parameters of zimeldine and norzimeldine were found.

Adult↗

PubMed1984

Relationship of N-demethylation of amiflamine and its metabolite to debrisoquine hydroxylation polymorphism.

The metabolism of the new reversible A-selective monoamine oxidase inhibitor amiflamine was studied in relation to polymorphic hydroxylation of debrisoquine in 24 healthy subjects. Amiflamine is metabolized by two consecutive N-demethylations. By construction of urinary recovery ratios analogous to that of debrisoquine/4-hydroxydebrisoquine, correlations between debrisoquine metabolic ratio and amiflamine/demethylated metabolites were significant and consistent within slow and rapid hydroxylators of debrisoquine. It is concluded that debrisoquine hydroxylation and amiflamine N-demethylation might be under common genetic regulation.

Administration, Oral↗