title: Effect of chloroquine and primaquine on antipyrine metabolism.
abstract: The effects of two antimalarial drugs, chloroquine and primaquine on antipyrine kinetics and metabolism have been studied in volunteers. Chloroquine (250 mg) given 2 h before antipyrine (600 mg orally) had no effect on salivary kinetics of antipyrine or on the urinary recovery of metabolites. Primaquine (45 mg) given 2 h before antipyrine (300 mg orally), increased antipyrine half-life (calculated from 0-24 h) from 12.7 +/- 3.2 (mean +/- s.d.) to 25.3 +/- 3.9 h and decreased clearance from 3.01 +/- 0.67 to 1.32 +/- 0.32 1 h-1. There was no change in the apparent volume of distribution. Antipyrine half life changed with time in the presence of primaquine and when calculated between 24 and 48 h had returned to control. After primaquine, the metabolic clearance (calculated from 0-24 h) of antipyrine to its three main metabolites, 3-hydroxymethylantipyrine, 4-hydroxyantipyrine and norantipyrine was significantly reduced. There was no selective effect on a particular metabolic pathway. There was no change in 6 beta-hydroxycortisol excretion (expressed as a ratio of total 17-hydroxy-corticosteroids) in the period 0-48 h following primaquine administration. The inhibition of hepatic metabolism by primaquine but not the structurally related chloroquine may be an example of a structure activity phenomenon and could be of clinical significance.
mesh_terms: D000328:Adult; D000983:Antipyrine / Q000378:metabolism*; D002738:Chloroquine / Q000494:pharmacology*; D006207:Half-Life; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D011319:Primaquine / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D002738:Chloroquine; D011319:Primaquine; D000983:Antipyrine