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

1 Two studies were carried out on acutely psychotic patients receiving chlorpromazine (100 mg) 8-hourly. 2 In the pilot study on five patients, plasma chlorpromazine concentrations fell over the course of 3 weeks of treatment and parallel changes were noted in the plasma half-life of antipyrine, salivation rate and handwriting length. 3 In the main study involving twelve patients treated for 15 weeks, the above findings were confirmed and were interpreted as indicating that chlorpromazine accelerated its own metabolism by inducing liver microsomal oxidising enzymes. No metabolites of chlorpromazine were detected in plasma. 4 The addition of phenobarbitone (50 mg) 8-hourly for 3 weeks, or orphenadrine (100 mg) 8-hourly for 3 weeks, resulted in a lowering of plasma chlorpromazine concentrations together with a further shortening of plasma antipyrine half-life. 5 Physiological effects of the additional treatments suggested that phenobarbitone lessens the effects of chlorpromazine by lowering body concentrations. However, orphenadrine acts more by virtue of its anticholinergic effects. 6 It was concluded that phenobarbitone and orphenadrine should not be prescribed routinely in patients receiving major tranquillisers. The need for the addition of orphenadrine should be assessed in each individual case.