Physiologic and clinical effects of chlorpromazine and their relationship to plasma level

Abstract

Physiologic and clinical effects of chlorpromazine and their relationship to plasma levelTen patients suffering from functional psychoses who had not received medication for one month were studied. After investigation before treatment, they received chlorpromazine in liquid form, 100 mg. every 8 hours for 5 to 6 weeks. Testing was carried out on Days 4,8,15,22,29, and 36 or 43 of treatment: (1) Blood samples were taken for chlorpromazine assessment at 0, 2, 4, and 6 hours after the morning dose; (2) blood pressure and pulse rate, pupil size, sweat gland activity, and electroencephalogram (EEG) were recorded at these times; (3) salivary secretion, EEG-evoked response, auditory reaction time, and handwriting tests were carried out at the 2 hour point; and (4) clinical ratings were made between 2 and 4 hours. Wide interpatient variation in plasma level was found; concentrations were maximal in the first 2 weeks, then consistently declined. Changes in the peripheral autonomic measures correlated with those in plasma level, but changes in the central measures were inconsistent. Plasma levels and clinical improvement were weakly related during the first 2 weeks of treatment only. Clinical improvement correlated with palmar skin conductance (sweating) and with some latencies of the electroencephalographic-evoked response. The determination of chlorpromazine plasma levels should be of use in investigating nonresponders and patients with severe autonomic effects.

Interactions of orphenadrine and phenobarbitone with chlorpromazine: plasma concentrations and effects in man.

“…This could be interpreted as a mixed effect, a reduction in plasma chlorpromazine concentration by both drugs, together with a further anticholinergic effect possessed by orphenadrine alone. Unlike our previous study (Sakalis et al, 1972), handwriting length was a particularly sensitive measure.…”

“…In a previous study (Sakalis, Curry, Mould & Lader, 1972), we found quite consistently that chlorpromazine concentrations rose during the first 8-15 days of treatment but then fell. Despite this fall, clinical improvement continued as did many physiological effects.…”

“…Full details of this technique have been described previously (Curry, 1968), and the reliability and validity of the technique as currently employed in the laboratories of the London Hospital Medical College have also been presented earlier (Sakalis et al, 1972). The lowest concentration detectable was 5 ng/ml in a 5 ml plasma sample.…”

Predictive indices for chlorpromazine therapy in schizophrenics.

“…Drug concentration in plasma seems to be only weakly correlated to the therapeutic effect (Sakalis et al, 1972;Rivera-Calimlim et al, 1973, 1976, 1978 and this low correlation may reside in the inter--individual differences in CPZ metabolism resulting in different levels of active and inactive metabolites in different patients (Sakalis et al, 1973(Sakalis et al, , 1977Mackay et al, 1974;Sakurai et al, 1975;Phillipson et al, 1977). The high protein binding of CPZ in plasma and the CSF/plasma ratio which seem to be an individual factor (Piafsky et al, 1978;Wode-Helgodt & Alfredson, 1981) may also contribute to this low correlation.…”

Plasma level studies in psychotropic evaluation.

“…However, from the eighth to the thirty-sixth day a steady decline in the overall level is seen, although there is still the expected rise and fall during each individual dosage period (Sakalis et al, 1972). Without necessarily quite knowing why, the psychiatrist tends to increase the dose during this time, so that the plasma level may stay elevated, but at a higher dose level.…”