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Antimalarial drugs

Drugs for the treatment of malaria.

Our overall objective is to obtain such pharmacokinetic, metabolic, toxicological and pharmacodynamic information on antimalarial drugs as to enable recommendation of safe and efficacious future artemisinin-based combination treatments (ACT).

The artemisinins have emerged as the most important new class of drugs in the treatment of malaria.

Most of the endoperoxides suffer from pharmacokinetic deficiencies such as short biological half-lifes. The pharmacokinetics of the original drug – artemisinin – is extremely complex with both dose and time dependency and with a potential for both inhibition and induction of drug metabolizing enzymes. With artemisinin-based combination treatments being deployed it is important that combinations are selected which do not have a problem with safety or efficacy due to inherent drug-drug interactions.

The metabolism of artemisinin endoperoxides is being investigated both with preclinical methods and in clinical studies.

Piperaquine

Piperaquine, a bisquinolone, is currently first-line treatment in some Southeast Asian countries and is under clinical investigation elsewhere. Although piperaquine is an “old” compound there is hitherto very limited knowledge concerning its human pharmacokinetics or metabolism. Our initial clinical studies indicate a typical quinolone multiphasic plasmaconcentration-time profile with a terminal half-life of about one month. Further characterization of piperaquine´s kinetics and metabolism is underway.

Modeling and simulation (M&S)

Mathematical models for the clinical antimalarial action of artemisinin and its derivatives in combination with other drugs are being investigated. These models may be used for the prediction of clinical effects after varying dosage regimens and drug combinations. Such models may also be explored in clinical trial simulations. M&S has been applied to further characterize the pharmacokinetics of amodiaquine and its active metabolite desethylamodiaquine in a pediatric patient population, aswell as PKPD for the combination lumefantrine artemether.
 

Pregnancy

 

Contact Information

Michael Ashton

Box 431 , 405 30 Göteborg

Visiting Address:
Medicinaregatan 13A

Phone:
+46 (0)31 786 34 12

Fax:
+46 (0)31 786 32 84

Page Manager: Webbredaktör|Last update: 3/13/2009
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