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Clinical Pharmacokinetics

, Volume 10, Issue 3, pp 187–215 | Cite as

Clinical Pharmacokinetics of Antimalarial Drugs

  • Nicholas J. White
Review Article

Summary

For the past 300 years antimalarial dosage regimens have not been based on pharmacokinetk information. However, now that this information is available, it is appropriate to examine current recommendations for prophylaxis and treatment.

In healthy subjects, the cinchona alkaloids (quinine and quinidine), primaquine and proguanil (chloroguanide) are all rapidly eliminated with half-lives (t½β) of between 6 and 12 hours. Hepatic biotransformation accounts for approximately 80, 96 and 50% of their total clearance, respectively. In malaria, the pharmacokinetic properties of quinine and quinidine are significantly altered with a decrease in the apparent volume of distribution (Vd), prolongation of the elimination half-life, and a reduction in systemic clearance (CL) that is proportional to the severity of infection. Red cell concentrations and plasma protein binding are both increased in severe disease. Parenteral quinine or quinidine should be given by slow intravenous infusion rather titan by intravenous or intramuscular injection, and a loading dose is necessary in severe infections.

Chloroquine (t½β 6 to 50 days) and mefloquine (t½β 6.5 to 33 days) have extensive tissue distribution and prolonged activity after a single dose. Both drugs are concentrated in erythrocytes and 55% of chloroquine and 98% of mefloquine in plasma is bound to protein. The pharmacokinetics of chloroquine are complex and, because of the extremely long β phase, difficult to accurately define. Pyrimethamine (t½ 35 to 175 hours) has more limited tissue distribution, plasma and erythrocyte concentrations are similar, and 85% of the drug in plasma is bound to plasma proteins.

The clearance of quinine, mefloquine and pyrimethamine appears to be higher in children than in adults.

Currently, most of the information available on disposition of antimalarial drugs in humans is derived from studies in healthy adult subjects. More information is required on their pharmacokinetics in malaria, pregnancy, and in young children.

Keywords

Malaria Chloroquine Quinidine Quinine Antimalarial Drug 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© ADIS Press Limited 1985

Authors and Affiliations

  • Nicholas J. White
    • 1
    • 2
    • 3
  1. 1.Tropical Medicine Unit, Nuffield Department of Clinical MedicineUniversity of OxfordUK
  2. 2.Faculty of Tropical MedicineMahidol UniversityBangkokThailand
  3. 3.Department of Tropical MedicineLiverpool School of Tropical MedicineUK

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