Plasma Chlorpromazine Research Articles

Clinical significance of plasma chlorpromazine levels

Clinical significance of plasma chlorpromazine levels

Correlation between plasma levels of prolactin and chlorpromazine in psychiatric patients

Plasma levels of chlorpromazine (CPZ) and prolactin were measured repeatedly in 14 psychiatric patients throughout CPZ treatment. Mean prolactin level was elevated in 11 subjects (all six women and five of eight men). Mean plasma prolactin correlated significantly with mean plasma CPZ but not with the dose of the drug. Only patients with mean plasma prolactin above 35 ng/ml developed Parkinsonian side-effects.

Chlorpromazine treatment of disturbed monkeys.

Four rhesus monkeys which were subjected to partial social isolation during the first 11 months of life and which had consistently exhibited patterns of grossly abnormal behavior during the 1½ years prior to the current study were treated with chlorpromazine. Three of the four subjects showed significant decreases in their self-disturbance behaviors on 7.5 mg/day of chlorpromazine given as the liquid concentrate by nasogastric intubation. The fourth subject showed no change. Plasma chlorpromazine levels confirmed absorption of the drug in all subjects.

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

Ten 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.

Chlorpromazine and Sleep in Psychiatric Patients

The effect of chlorpromazine on nine patients with sleep disturbance was investigated. The results showed that chlorpromazine given at bedtime coincided with a marked increase in actual sleep time as exemplified by a significant decrease in intermittent wakefulness. Total REM time was increased proportionately to the increase in actual sleep. In a more extensive study in four patients, it was found that the administration of daytime chlorpromazine (100 mg) had no direct effect on sleep as compared to placebo. In contrast, bedtime chlorpromazine was associated with significant changes in various sleep parameters. That the time course of chlorpromazine administration is responsible for the differential effect on sleep is supported by the preliminary investigation with plasma chlorpromazine levels.

Chlorpromazine plasma levels and effects.

THE metabolism and tissue distribution of chlorpromazine have been studied extensively,^1,2yet attempts to correlate clinical effects with variations in the fate and disposition of the drug have been unrewarding.^3-7In most studies of this type the drug and its metabolites have been assayed in urine by nonspecific methods. It is becoming increasingly apparent, however, that for many drugs responses are related more closely to plasma levels of the drug (or active metabolites) than to urinary excretion rates of the drugs and their inactive metabolites.^8,9Individual variation in response to drugs may be caused by variations in plasma levels, resulting from variations in rates of absorption and metabolism. Variations in plasmalevels are particularly marked in the case of highly lipid-soluble drugs, such as those used in psychopharmacology.¹⁰If these variations could be controlled by dosage regimens^10,11that would