PubMed Health⌕ Search

Biomedical subjects

A D Broadhurst

Publications and source records attributed to A D Broadhurst.

13 recordsLinked to original sources

Plasma levels and clinical response during treatment with clomipramine.

The plasma levels of clomipramine (CI) and its major metabolite desmethylclomipramine (DMCI) may be related to clinical response during treatment of depression. Not all workers have been able to demonstrate such a relationship. The many factors which may affect clinical response include sample selection, assessment and its quantification and kinetic factors. A further investigation into the relationship between plasma levels and response was, therefore, carried out taking these into account and attempting to control them. Sixty-two patients with depressive illness were included. The plasma levels of CI + DMCI as measured on the 28th day of treatment were correlated against clinical response at the time. Patients with the highest combined plasma levels showed the best response. Patients with intermediate plasma levels showed more modest response, whilst lowest plasma levels tended to be shown by patients who exhibited an inadequate response or who relapsed during subsequent outpatient follow-up. The threshold value for satisfactory antidepressant effect appeared to be a combined CI + DMCI plasma level of 160-200 mg/ml.

Adult↗

The effect of single doses of penbutolol and propranolol L.A. on psychomotor performance.

The effect of single oral doses of penbutolol (40 mg) and propranolol L.A. (160 mg) on psychomotor performance of 12 normal individuals has been investigated. Subjects were randomly administered penbutolol, propranolol L.A. and placebo according to a double-blind, three-part cross-over design. At 3 h post-dosing both penbutolol and propranolol L.A. significantly increased (P less than 0.001) complex reaction times when compared to placebo. By 24 h post-dosing the mean complex reaction times for penbutolol and propranolol L.A. were not significantly different from placebo.

Adult↗

Double-blind trial with oral versus intravenous clomipramine in primary depression.

Intravenous clomipramine and oral clomipramine at a daily dose of 2 mg/kg body weight were compared in a double-blind study of 40 inpatients with primary depressive illness. No significant differences between the two routes of clomipramine administration were found, either in response or in side effects. Steady state was not attained at the 4th week of treatment in 30% of patients. However, combined plasma levels of clomipramine (CI) plus desmethylclomipramine (DMCI) were similar in the two groups at all stages of treatment. The only significant pharmacokinetic difference that was found was in the ratio of DMCI to CI, which was higher among the patients who received the drug orally, but this did not correlate with clinical response. Conversely, Day 28 plasma concentrations of CI, DMCI, and the sum CI + DMCI were significantly related to clinical outcome in the patients treated orally. Among the patients who received the drug intravenously only CI was significantly associated with the percentage reduction of symptoms. By pooling the two groups, CI, DMCI, and their sum all bore relationships to clinical response significant at the 0.01 level.

Administration, Oral↗

Comparison of effect on psychomotor performance of single doses of propranolol and acebutolol.

Propranolol has recently been shown to produce some impairment of psychomotor performance in human volunteers. This beta-blocking compound, however, is lipophilic and readily penetrates the blood-brain barrier to gain access to the central nervous system. Acebutolol has a lower lipid solubility. A study was carried out, therefore, to compare the psychomotor effect of the two beta-blocking drugs. Any subjectively experienced side-effects were also recorded. Ten healthy volunteers were given single doses of 40 mg propranolol, 100 mg acebutolol and placebo on a random double-blind basis and the effect, if any, on performance was measured using a particularly sensitive complex reaction time technique. Propranolol produced a significant prolongation of complex reaction time when compared with placebo or acebutolol. Acebutolol did not significantly increase complex reaction time over the placebo value. Two subjects reported mild feelings of 'muzziness' after taking propranolol. No side-effects were reported after acebutolol.

Acebutolol↗

The effect of propranolol on human psychomotor performance.

Despite their widespread usage the effect of beta blockers on human performance has been only sparsely studied and results of investigations are discrepant. This study examines the effect of one of the most commonly prescribed beta adrenergic blocking drugs, propranolol, on psychomotor function. To demonstrate the sensitivity of the test method and to provide some basis for comparison, the effect of small doses of sodium amylobarbitone on psychomotor performance is also measured. Results indicate that propranolol in a single dose of 40 mg produces a small but significant decrement of performance, an effect comparable to that of 25 mg of sodium amylobarbitone. Habituation to chronic administration of propranolol at a daily dose level of 120 mg is also apparent. The clinical significance of these effects, particularly in aviation medicine, is discussed.

Adult↗

Clinical response and tricyclic plasma levels during treatment with clomipramine.

Fifty depressed in-patients at two psychiatric units, one in Italy the other in England, were treated with clomipramine, either orally, or intravenously and orally. A comparison of clinical response with plasma levels of clomipramine and its metabolite, desmethylclomipramine, showed clear relationships especially in the case of desmethylclomipramine. In the intravenously-treated group this was linear, in the orally-treated group it was curvilinear. Plasma levels of desmethylclomipramine and administered clomipramine correlate highly. These findings, together with the fact that significant clinical improvement was observed in only 55% of the patients, suggest that titration of the administered dose to obtain more effective plasma levels of the metabolite might improve the clinical response to the drug in some patients.

Administration, Oral↗