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Biomedical subjects

S I Ankier

Publications and source records attributed to S I Ankier.

At least 19 recordsLinked to original sources
PubMed1991

A pharmacokinetic and dynamic study of single nightly doses of conventional and controlled release formulations of trazodone.

We studied the pharmacokinetics and dynamics of single evening oral doses of conventional capsules (100 mg) and a controlled release formulation (150 mg) of trazodone in 12 fasting and non-fasting young healthy volunteers. When corrected for the different doses used, there was no significant difference among the areas under the plasma concentration-time curves (AUC) for the conventional capsules and the controlled release tablets under fasting and non-fasting conditions. Both conventional and controlled release formulations were followed by a reduction in critical flicker fusion threshold (CFFT) and this effect was not influenced by the administration of food before dosing. After both conventional and controlled release formulations, blood pressure was significantly lower when medication had been given in the fasting state than when it had been given after food. The frequency of adverse symptoms was greater after the controlled release (150 mg) than after the conventional (100 mg) formulation. We conclude that there is no obvious advantage to the controlled release formulation (150 mg) and that conventional trazodone (100 mg) should be taken after food when it is given at night.

Adult↗
PubMed1990

ICI 141,292 (epanolol)--pharmacokinetics after single and repeated oral administration in the elderly with moderate renal impairment.

The pharmacokinetics of ICI 141,292 (epanolol) were studies over 3 days after a single oral 200 mg dose and then over 24 h after 12 consecutive daily oral 200 mg doses in 16 elderly subjects (aged 65 to 94 years) with moderate renal impairment (mean creatinine clearance 33.2 ml.min-1). There was wide inter-individual variability in peak plasma ICI 141,292 concentrations (Cmax) but no significant difference was found between mean Cmax after a single dose (44.3 ng.ml-1) and after 12 doses (37.4 ng.ml-1). The mean observed time to peak plasma ICI 141,292 concentration (tmax) after a single dose (1.61 h) did not differ significantly from that after 12 doses (1.75 h). On several occasions an analytically significant second peak in ICI 141,292 plasma concentration was observed. Following the peak(s), the plasma concentrations declined biphasically and a mean terminal phase plasma half-life (t1/2) of 28.3 (range 10.2-84.8) h was calculated after a single dose. The inter-individual variability in the area under the plasma concentration-time curve to 24 h AUC (0-24) was 54 fold but there was no significant difference between AUC (0-24) after a single dose (mean 226.0 ng.h.ml-1) and AUC (0-24) after 12 consecutive doses of ICI 141,292 (mean 232.4 ng.h.ml-1). The results show that consecutive daily administration of 12 oral doses of ICI 141,292 (200 mg) does not result in significant accumulation of drug in elderly subjects with moderate renal impairment.

Administration, Oral↗
PubMed1989

A double-blind placebo-controlled study of the efficacy and tolerability of ebastine against hayfever in general practice patients.

Ebastine is an H1 antihistamine. Using a double-blind, parallel group randomized study design, the efficacy and the tolerability of oral ebastine (10 mg daily escalating to 40 mg daily according to clinical need) was compared over 4 weeks during 1986 with matching placebo in 40 general practice patients suffering from hayfever. Ebastine (19 patients) was more effective (P less than 0.05) than placebo (21 patients) against symptoms of running nose, itching nose, sneezing and blocked nose. Ebastine was superior to placebo in respect of the total symptom score as well as when judged by the investigators' and the patients' opinion of overall efficacy. Ebastine caused few adverse events, none of which resulted in a patient being withdrawn from treatment. Significantly more patients were withdrawn because of inefficacy from the placebo (n = 12) than from the ebastine (n = 3) treatment group (P less than 0.02). It is concluded that ebastine (10-40 mg daily) is an effective and well tolerated treatment for hayfever.

Adult↗
PubMed1989

Trazodone conventional and controlled-release formulations: pharmacodynamic effects after single and repeated administration.

In a double-blind study, the pharmacodynamic effects of single and repeated doses of two formulations of trazodone were compared in 14 healthy young volunteers (6 men and 8 women). They received either 100 mg trazodone conventional capsules or 150 mg controlled-release tablets daily at 08.00 hours for two 7-day periods separated by a 'wash-out' period of 2 weeks. Blood pressure standing and lying, critical flicker fusion frequency and manual dexterity were measured on Days 1 and 7 of each session before and at intervals up to 8 hours after the dose. Manual dexterity was tested by measuring the time taken to drop 50 airgun pellets down a narrow tube. A daily pre-dose blood sample was also taken for measurement of trazodone to check compliance and to confirm that steady state had been achieved. Steady state plasma concentrations were reached by Day 2 of repeated dosing on both treatments. There was a trend towards shorter duration of the expected depressant effect of trazodone on critical flicker fusion frequency and manual dexterity on Day 7 for both treatments, which was significantly different between treatments for manual dexterity (p less than 0.001): for the controlled-release tablet, manual dexterity performance was better on Day 7 than on Day 1 at all times after dosing, whereas for the conventional capsule manual dexterity was worse on Day 7 than on Day 1 until 4 and 8 hours after dosing, when performance was better than on Day 1. In this study, both formulations of trazodone caused the expected negative effects on psychomotor function. Further studies would be required to confirm the apparent advantage of the controlled-release tablet in the test of manual dexterity.

Adult↗
PubMed1989

A multi-centre, placebo controlled comparative study between 200 mg and 400 mg celiprolol in patients with mild to moderate essential hypertension.

A two-centre, double-blind, placebo controlled, randomized 3-way crossover study was undertaken to assess the efficacy, tolerability and safety of celiprolol in mild to moderate essential hypertension. A 4-week single-blind placebo run-in/screening period, during which no antihypertensive medication was given, was followed by 3 consecutive 4-week treatment periods with placebo or celiprolol (200 mg or 400 mg daily). At the end of the 4-week placebo run-in/screening period, 26 hospital out-patients with a seated mean blood pressure (systolic/diastolic) of 161.4/101.7 mmHg and a mean pulse rate of 75 beats/min entered the double-blind crossover phase of the study. Results showed that there was no significant difference in seated mean systolic or diastolic blood pressure between 200 mg celiprolol daily (149.2/92.3 mmHg) and 400 mg celiprolol daily (149.1/92.5 mmHg). However, mean seated systolic and diastolic blood pressures were significantly (p less than 0.05) lower on celiprolol than on placebo (157.1/98.2 mmHg). Neither dose of celiprolol had a significant effect on seated pulse rate. No patient was withdrawn due to an adverse event and no laboratory assessment outside the normal range was reported to be of any clinical significance. It is concluded that oral celiprolol, 200 mg or 400 mg daily, is effective and well tolerated for controlling mild to moderate essential hypertension. Since both doses had very similar effects on blood pressure there is no advantage in this group of patients for the 400 mg daily dose of celiprolol.

Administration, Oral↗
PubMed1988

Mianserin and trazodone for cardiac patients with depression.

In a placebo controlled double-blind cross-over study, the cardiovascular and antidepressant effects of three weeks' treatment with mianserin (30-80 mg daily) and trazodone (150-400 mg daily) were studied in depressed patients who had co-existant cardiac disease. In 14 of the 16 patients, no haemodynamic deterioration occurred with either drug. Two patients withdrew from the study. One with coronary artery disease, whose concomitant medication included a calcium-antagonist and a beta-adrenoceptor blocker and who developed severe postural hypotension after his first dose of trazodone while the other had an increased frequency of transient cerebral ischaemic attacks with both mianserin and trazodone, but not with placebo. Mianserin and trazodone are comparable for both antidepressant efficacy and paucity of cardiovascular effects. Although unwanted effects were generally mild, the incidence of dizziness was greater in those patients receiving trazodone. Caution is advised, however, when prescribing either drug to patients with transient cerebral ischaemic attacks or those with coronary artery disease receiving medication.

Adult↗
PubMed1988

Pharmacokinetics of flupirtine in elderly volunteers and in patients with moderate renal impairment.

The pharmacokinetics of flupirtine after a single oral dose of 100mg have been studied in patients with moderate renal impairment and in healthy elderly subjects aged 66-83 years. Mean elimination half-life of flupirtine was higher in elderly patients than in younger normal subjects, and this was associated with an increased maximum serum concentration and reduced clearance. The mean half-life in patients with renal impairment was higher than in normal subjects. There was no correlation between observed elimination half-life and degree of renal impairment, but the creatinine clearance of most patients fell in a narrow range between 43 and 60 ml/min. In the light of these results and until further information is available, it would be prudent to start treatment of patients who are elderly or have evidence of renal impairment with half the dose of flupirtine recommended for younger patients with normal renal function.

Age Factors↗
PubMed1988

Chlortenoxicam pharmacokinetics in young and elderly human volunteers.

The pharmacokinetics of chlortenoxicam, a new non-steroidal anti-inflammatory drug, have been compared in young and elderly healthy human volunteers. Chlortenoxicam was found to have a relatively short mean elimination half-life of about 4 hours, with considerable inter-subject variability, but there was no significant difference between young and elderly subjects. There was no evidence of accumulation with repeated administration. No unchanged chlortenoxicam was found in urine from any subject, suggesting that it undergoes extensive metabolism in man.

Adult↗
PubMed1988

Quazepam. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in insomnia.

Quazepam is a trifluoroethyl benzodiazepine hypnotic with a half-life of 27 to 41 hours, which has been shown to induce and maintain sleep in the short to long term (up to 4 weeks) treatment of patients with chronic or transient insomnia. Although its hypnotic efficacy has been well characterised against placebo, there are few clinical studies in comparison with established hypnotics, particularly over long term administration. However, preliminary evidence suggests that quazepam 15 to 30 mg is as effective as flurazepam and triazolam in usual therapeutic doses, and causes minimal rebound insomnia following its withdrawal, unlike rapidly eliminated benzodiazepines such as triazolam. The lack of rebound phenomena is likely to be attributable to the 'carryover' effects occurring after discontinuation of quazepam, which has pharmacologically active metabolites with half-lives of elimination similar to or longer than that of the parent drug. Probably because of the long half-lives of quazepam's metabolites, daytime sedation, fatigue and lethargy are the most frequently reported side effects. These side effects are most intense with the 30 mg dose and least with the 7.5mg dose, which has not been studied extensively. Hence, quazepam is an effective hypnotic which may be particularly suitable for short or medium term use in patients in whom withdrawal effects or rebound insomnia may be especially bothersome. Further definition of certain characteristics of its profile--such as its long term use and potential for development of tolerance or dependence, effects on psychomotor skills, efficacy of the 7.5mg dose, and suitability in elderly patients and patients with chronic organic diseases--will assist in more clearly defining its ultimate place in therapy.

Anti-Anxiety Agents↗
PubMed1987

Pharmacokinetics of loprazolam and its principal metabolite in young subjects and elderly hospital patients.

1. The pharmacokinetics of loprazolam and its principal pharmacologically active metabolite, the piperazine N-oxide, were compared in young subjects (aged 21-25 years) and elderly patients (aged 63-86 years) following single oral evening doses (0.5 mg and 1 mg). 2. Plasma loprazolam was assayed by a specific h.p.l.c./g.c. method. The N-oxide metabolite was assayed by gas chromography. 3. Mean times to peak plasma concentration of loprazolam did not differ significantly between young and elderly subjects and ranged from 1.6-2.7 h. There was, however, a longer mean time to peak concentration of the N-oxide metabolite in the elderly but this was only statistically different after the 0.5 mg dose (4.5 mg young, 6.4 h elderly). 4. Mean peak plasma concentrations of loprazolam did not differ significantly between young and elderly nor did plasma concentrations of the N-oxide metabolite. 5. Although the mean elimination half-life of loprazolam was not statistically significantly different between young and elderly subjects (range 10.9-16.0 h) there was a trend towards somewhat longer half-lives in the elderly. Furthermore, there was a small but significant increase in the half-life of the N-oxide metabolite in the elderly after the 1 mg dose from 11.7 h to 16.7 h. 6. The areas under the plasma concentration time curves for both loprazolam and its N-oxide were greater in the elderly being some 50-68% (mean 132.0 and 111.5 ng/ml h) above those found in young subjects (mean 89.8 and 66.0 ng/ml h).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Evaluation of possible interactions between ethanol and trazodone or amitriptyline.

The pharmacodynamic effects of single doses of trazodone (100 mg), amitriptyline (50 mg) or placebo either alone or with ethanol (0.5 ml/kg) were investigated in 6 healthy volunteers in a double-blind crossover study. Plasma concentrations of the drugs and ethanol were also measured. Pharmacodynamic tests were critical flicker fusion frequency threshold (CFF), choice reaction time (CRT), manual dexterity, a digit span test and visual analogue scales. Blood ethanol concentrations were not influenced by the co-administration of either antidepressant. tmax for trazodone was prolonged by ethanol but the other pharmacokinetic parameters for trazodone and amitriptyline were not influenced by ethanol. Trazodone and amitriptyline caused the expected profound depressant effects on CFF, CRT, manual dexterity and on the rating scales for drowsiness, 'clearheadedness', aggression and disinhibition. Ethanol alone impaired manual dexterity, increased drowsiness, reduced 'clearheadedness' and also tended to reduce feelings of aggression. In combination with either trazodone or amitriptyline, ethanol caused little additional effect except in the case of manual dexterity, which was further impaired. This result may reflect the profound effects of the antidepressants alone and does not suggest that it is safe for patients receiving antidepressant medication to take ethanolic drinks.

Adult↗
PubMed1985

Pharmacokinetics and pharmacodynamics following single and repeated nightly administrations of loprazolam, a new benzodiazepine hypnotic.

The pharmacokinetics of oral loprazolam and pharmacodynamic responses on the morning following nightly drug administration were examined after single and after seven consecutive 1 mg doses in six non-fasting healthy subjects. The serum concentration-time profiles for unchanged loprazolam measured by a specific high pressure liquid chromatography/gas chromatography (h.p.l.c./g.c.) method and for benzodiazepine material measured by radioimmunoassay (RIA) were qualitatively similar although RIA levels were consistently higher. Approximate elimination half-life of unchanged loprazolam after single doses was 8.0 h. For RIA measured material, approximate half-life was 11.7 h following acute administration and 12.8 h after seven consecutive doses. Compared to results after single doses, maximum serum concentration and AUC were greater following 1 week's treatment. Using RIA results, the increases were 27.2% (95% CL 6.9 to 47.4%) and 35.1% (95% CL 15.8 to 54.3%) respectively and using h.p.l.c./g.c. data, 11% (95% CL - 22.6% to 44.5%) and 41% (95% CL - 50.9 to 133.0%). After repeated doses of loprazolam, there were no significant changes with respect to results after single doses in psychomotor function assessed objectively by critical flicker fusion threshold or choice reaction time, or in sleep quality or behaviour on awakening assessed subjectively by 10 cm analogue scales. Mean time to maximum serum concentration was 4.95 h with considerable inter-individual variability (range 1-12 h) and there was a lag time of 1-1.5 h before drug was detectable in blood.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Single dose pharmacokinetics and pharmacodynamics of oral loprazolam in the elderly.

The pharmacokinetics of the benzodiazepine hypnotic, loprazolam (1.0 mg orally), and the pharmacodynamic response to single oral doses (0.5 mg and 1.0 mg) have been compared in young and elderly healthy volunteers. No difference between the groups in peak plasma concentration (Cmax) or in the time to peak (tmax) was found, but the elimination half-life t1/2,z and area under the plasma concentration-time curve (AUC) were significantly greater in the elderly group. The immediate effects of loprazolam on all three performance tests used (postural sway, critical flicker fusion threshold (CFFT) and choice reaction time (CRT] and on subjective sedation tended to be more pronounced in the elderly subjects, though intersubject variability in response was high in both groups. The corresponding plasma concentrations did not differ significantly between the two groups. The higher (1.0 mg) dosage was associated with significant residual (11 h) impairment of standing steadiness in the elderly subjects. No other hangover effects were observed. The results are compatible with previous evidence of increased 'sensitivity' to benzodiazepines in the elderly and suggest that a lower (0.5 mg) starting dose of loprazolam would be appropriate for older recipients. Further investigation would be necessary to establish whether clinically relevant accumulation of loprazolam occurs in the elderly following repeated dosage.

Administration, Oral↗