Clinical significance of plasma chlorpromazine levels. I. Plasma levels of the drug, some of its metabolites and prolactin during acute treatment

Wiles D.H.; Kolakowska T.; McNeilly A.S.; et al.

Dept. Psychiat. Res. Unit, Univ. Oxford, Littlemore Hosp., Oxford, Great Britain

Seventeen acute psychotic patients were studied in the course of chlorpromazine (CPZ) treatment. Blood samples were taken weekly both before and two hours after the morning CPZ dose. Plasma levels of CPZ, CPZ sulphoxide (CPZ SO) monodesmethylated CPZ (NOR1CPZ) and 7 hydroxy CPZ (7OH CPZ) were estimated by gas chromatography. Plasma prolactin, luteinizing hormone, testosterone and oestrogens were measured by radioimmunoassay. Six of the seven patients who showed no clinical improvement had plasma CPZ levels equal to or higher than those of patients who improved. 'Non responders' had a greater proportion of CPZ SO in pre dosage samples. The occurrence of parkinsonian side effects was associated with a mean plasma CPZ of > 50 ng/ml and a mean plasma prolactin of > 30 ng/ml two hours after dosage. The elevation of prolactin preceded the onset of parkinsonian symptoms by 1-2 weeks. There was a significant positive correlation between mean plasma prolactin and mean plasma CPZ levels. The prolactin response may prove a useful index of the central antidopaminergic effect of neuroleptic drugs.

Keywords: clinical study; dose response; estrogen therapy; metabolite; parkinsonism; drug therapy; plasma; psychosis; serum; major clinical study; therapy; oral drug administration; drug response; drug blood level; normal value

PSYCHOL. MED. 6/3 (407-415) 1976