Effect of cotrimoxazole on the response to phenylalanine loading in man

Abstract

Cotrimoxazole impairs the L-phenylalanine tolerance of control subjects as judged by the time course of the plasma phenylalanine concentration and the plasma ratios [phenylalanine] / [tyrosine] after oral and intravenous loading with phenylalanine. These subjects are presumed not to be heterozygous for any of the abnormal recessive genes which cause hyperphenylalaninaemia when they are present in the homozygous state. Patients with classical phenylketonuria did not show this effect. Cotrimoxazole did not affect the renal clearance of phenylalanine. The effect appears to be virtually entirely due to the trimethoprim component as opposed to the sulphamethoxazole component of Cotrimoxazole. The evidence presented is compatible with the view that the drug inhibits phenylalanine hydroxylation in the patients' tissues, presumably by inhibiting dihydrobiopterin reductase. We suggest that it may be possible to utilise the observed effect of cotrimoxazole on phenylalanine hydroxylation to identify in vivo those hyperphenylalaninaemic patients who have residual phenylalanine hydroxylase activity.