当前位置： SCI文献检索 > CLINICAL PHARMACOKINETICS期刊下所有文献 > Clinical pharmacokinetics of antimalarial drugs.

Clinical pharmacokinetics of antimalarial drugs.

Abstract：

:For the past 300 years antimalarial dosage regimens have not been based on pharmacokinetic 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 (t1/2 beta) 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 than by intravenous or intramuscular injection, and a loading dose is necessary in severe infections. Chloroquine (t1/2 beta 6 to 50 days) and mefloquine (t1/2 beta 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 beta phase, difficult to accurately define. Pyrimethamine (t1/2 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.

journal_name

Clin Pharmacokinet

journal_title

Clinical pharmacokinetics

authors

White NJ

doi

10.2165/00003088-198510030-00001

subject

Has Abstract

pub_date

1985-05-01 00:00:00

pages

187-215

issue

eissn

0312-5963

issn

1179-1926

journal_volume

pub_type

杂志文章,评审

在线工具

Clinical pharmacokinetics of antimalarial drugs.