Pharmacokinetic Study of Primaquine and Dihydroartemisinin-Piperaquine in Healthy Subjects
Status:
Completed
Trial end date:
2012-09-01
Target enrollment:
Participant gender:
Summary
The observed changes of P. falciparum sensitivity to artemisinin leads to the intensification
of early detection as well as treatment monitoring in malaria infection. It is widely
accepted that the development of resistance can be delayed by the use of combination therapy,
especially artemisinin-based combination therapies (ACTs). The resistance problem is
considered extremely serious and as the consequence WHO has recommended that all monotherapy
for malaria should be stopped Current WHO guideline recommends the drug combination regimens
using ACT with effective partner medicines to decrease the risk of development or spreading
of artemisinin resistance.
Dihydroartemisinin-piperaquine (DHA-PQP); the fixed-dose combination of Dihydroartemisinin
(DHA) and Piperaquine phosphate (PQP) is now one of the recommended drugs by WHO as the oral
treatment for uncomplicated P. falciparum. DHA-PQP composes of both blood schizonticidal
drugs, with different mechanism of action and different half-life to improve the therapeutic
efficacy and to prevent the development of drug resistance to the individual drug. Moreover,
it is beneficial for the mutual protection against resistance and long lasting protection
against new infection, due to long half-life of PQP.
Primaquine is an effective gametocytocidal for P. falciparum transmission prevention and as
tissue killing for the radical cure in Plasmodium vivax and Plasmodium ovale infection. It
will be given only in the presence of other antimalarials, so it is necessary that the data
of the potential drugs interaction of primaquine and DHA-PQP should be characterized. It is
inevitable that in the near future, Dihydroartemisinin-piperaquine (DHA-PQP) and primaquine
combination treatment becomes necessary. These drugs are metabolized by cytochrome P450
enzyme which potentially causes pharmacokinetic alteration, resulting in clinically
significant drug-drug interactions that can cause unanticipated adverse reactions or
therapeutic failures because of the suboptimal exposure of the parasite.
This study is planned to evaluate potential pharmacokinetic interaction of orally
administered primaquine (PQ) and dihydroartemisinin-piperaquine (DHA-PQP) in healthy adult
subjects. The results of these interaction studies are important in order to provide clinical
guidance for the optimum combination of primaquine and DHA-PQP treatment regimens in malaria
infections.