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Biomedical subjects

W Yisak

Publications and source records attributed to W Yisak.

7 recordsLinked to original sources
PubMed1999

Single dose pharmacodynamics of thioridazine and remoxipride in healthy younger and older volunteers.

Phenothiazines are widely used in older patients, but little experimental work has been carried out in this age group. Two groups of healthy volunteers, a younger group (Y: six males and six females, aged 20-42 years) and an older group (O: six males and eight females, aged 65-77 years) took part in a randomized double-blind three-period crossover study in which they received by mouth single doses of thioridazine (Y: 50 mg; O: 25 mg) remoxipride (Y: 100 mg; O: 50 mg) or placebo. Measures of central nervous system (CNS) and haemodynamic function were carried out before drug administration and at 1.5-h intervals up to 9 h post-dose, and blood samples were collected over a 24-h period. No significant differences in dose-corrected pharmacokinetic variables were found between the two groups. There was evidence of marked CNS depressant effects of thioridazine from both objective and subjective measures. The effects for remoxipride were similar, though generally less marked. After allowance was made for dose, there was little indication of any difference in degree of CNS depression between the two age groups. Haemodynamic measures showed orthostatic reductions in blood pressure with thioridazine which were particularly marked in the older group, who also showed lower compensatory increases in pulse rate. These results indicate potential problems with orthostatic hypotension with thioridazine in older patients. CNS depression may also be a problem, especially in patients with compromised cholinergic function.

Adult↗
PubMed1993

Interaction study between remoxipride and biperiden.

Twelve healthy male volunteers took part in a double-blind randomised cross-over study composed of three treatment sessions: remoxipride 100 mg; remoxipride 100 mg plus biperiden 4 mg; and biperiden 4 mg. Plasma and urine concentrations of remoxipride and biperiden, plasma prolactin levels, salivary flow and adverse events were recorded to assess pharmacodynamic interactions. Remoxipride and biperiden had no effect on each other's plasma concentrations. Biperiden did not affect the urinary recovery or renal clearance of remoxipride. Prolactin levels were unaffected by biperiden but increased following remoxipride administration. Differences in prolactin Cmax and tmax following remoxipride versus concomitant (remoxipride + biperiden) treatment were not statistically significant. However, a slight but statistically significant (P = 0.04) increase in prolactin AUC was observed after concomitant treatment. No significant differences could be observed between the recorded salivary flow in all the treatment sessions. Single doses of remoxipride and biperiden showed no pharmacokinetic or pharmacodynamic interaction.

Adult↗
PubMed1990

Tolerability and pharmacokinetics of remoxipride after intramuscular administration.

A study was undertaken in seven schizophrenic patients to evaluate the tolerability and examine the pharmacokinetics of intramuscularly administered remoxipride after a single 200 mg dose and at steady state following repeated doses of 200 mg twice daily for one week. Comparisons of AUC, t1/2 and tmax using the Wilcoxon's signed rank test showed no significant difference between single dose and steady state indicating that the pharmacokinetics of intramuscular remoxipride were linear. The steady-state Cmax was found to be significantly larger than that after single dose and the increase was accounted for by the predicted accumulation factor, assuming linear kinetics. Although the inter-individual variability in plasma concentrations was large, the intra-individual variability was low as shown by the reproducibility of the single-dose and steady-state plasma curves. Remoxipride, administered intramuscularly, was well tolerated.

Adolescent↗
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↗
PubMed1990

Pharmacokinetics of remoxipride in elderly psychotic patients.

The pharmacokinetics of remoxipride when given as single doses of 50 mg and repeated doses of 50 mg, 100 mg, and 200 mg twice daily to 10 elderly psychotic patients (71-89 years) were compared with the findings of two other studies to reveal any age-related differences. The three studies comprised a total of 38 patients in three distinct age groups: elderly (71-89 years), middle-aged (46-69 years) and young (19-36 years). AUC, Cmax and Cmin of both total and unbound remoxipride increased with increasing age. The unbound fraction was similar in the three age groups. The half-life was prolonged in the elderly, most probably caused by a decrease in intrinsic clearance. A two-fold increase in AUC of both total and unbound concentrations was observed in the elderly group compared to the young, suggesting that patients over 70 years in general require half the dose needed by young adult patients. In general, the pharmacokinetics of remoxipride in the elderly are linear.

Adult↗
PubMedDate not supplied

Disposition of oral [14C]cefcanel daloxate hydrochloride in healthy male subjects.

The pharmacokinetics of the main metabolites of cefcanel daloxate hydrochloride, a new oral cephalosporin diester prodrug, was investigated. Cefcanel is antimicrobially active. After oral administration of a single dose of [14C]cefcanel daloxate hydrochloride to 7 healthy male volunteers (group A), plasma concentrations (t1/2 approximately 1 hr) and excretion of radioactivity, cefcanel (Aer = 38.2 +/- 3.8%, t1/2 approximately 1 hr), mandelic acid glycine conjugate (Aer = 3.7 +/- 0.5%, t1/2 approximately 15 hr) and N-mandelyl-2-aminoethanol (Aer = 7.5 +/- 3.0%) were evaluated. The absolute oral bioavailability of cefcanel was approximately 40% after administration of cefcanel daloxate hydrochloride and the extent of urinary excretion of cefcanel, mandelic acid glycine conjugate, and N-mandelyl-2-aminoethanol after an equimolar intravenous administration of cefcanel, were determined in a separate, similar group of volunteers (N = 12, group B). Total plasma clearance of cefcanel was 179.1 +/- 22.4 ml/min/1.73 m2 after intravenous administration. Renal clearances of cefcanel were 173.9 +/- 95.6 (po, group B), 166.6 +/- 31.9 (i.v., group B), and 136.3 +/- 16.1 ml/min/1.73 m2 (po, group A). Cefcanel was almost completely (92.6 +/- 7.3%) excreted in the urine as unmetabolized drug after intravenous administration (group B). However, when cefcanel daloxate hydrochloride was administered orally, more than 30% of the total urinary excretion was due to metabolites other than cefcanel. A large proportion of these metabolites were formed at a late stage, in the absence of systemic cefcanel. It is probable that biotransformed materials, distinct from cefcanel, were formed in the gastrointestinal tract and slowly absorbed rather than being systemic products of metabolic degradation of cefcanel.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗