THE EFFECT OF CHLOROQUINE ON THE PHARMACOKINETICS AND METABOLISM OF PRAZIQUANTEL IN RATS AND IN HUMANS

It is likely that a proportion of people treated with the anti-schisto somicidal drug praziquantel (PZQ) is also taking other drugs such as c hloroquine (CHQ), a widely used anti-malarial. The effect of CHQ on th e pharmacokinetics and metabolism of PZQ in rats and in humans was the refore studied. CHQ decreased the bioavailability of PZQ and reduced i ts maximum serum concentrations to a significant extent in rats and in humans. The clearance was increased to a statistically significant ex tent in rats but not in humans because of the wide interindividual var iation. The effect of CHQ on PZQ pharmacokinetics was unexpected since drugs that inhibit hepatic drug metabolism usually increase the bioav ailability of PZQ. We found that CHQ inhibits non-competitively the me tabolism of PZQ to its major metabolite, 4-hydroxy-praziquantel, with a K-i of 1.65 mM in rat hepatic microsomes. Maximum concentrations att ained by CHQ in serum, however, are low compared to the K-i value and significant inhibition is therefore unlikely in vivo. The explanation for CHQ's effect on the pharmacokinetics of PZQ may be due to other ef fects of CHQ rather than to a direct effect on drug-metabolizing enzym es.