Effect of Plasmodium falciparum malaria infection on the plasma concentration of alpha 1‐acid glycoprotein and the binding of quinine in Malawian children.

Abstract

3 The mean unbound QN fraction was significantly less (P < 0.00001) in patients with malaria (0.128 ± 0.037) than in controls (0.193 ± 0.051) and significantly higher (P = 0.02) in convalescence (0.153 ± 0.067) than during acute illness. 4 There were highly significant negative correlations between plasma AGP concentration and the free QN fraction in spiked plasma samples (r = -0.534, P < 0.0001, n = 93) and in clinical samples (r = -0.484, P < 0.00001, n = 225). There was a significant positive correlation between plasma concentrations of AGP and another acute phase reactant, C reactive protein (P < 0.001).

Interactions among primaquine, malaria infection and other antimalarials in Thai subjects.

“…This compound has been shown to be the major plasma metabolite in man (Mihaly et al, 1984) although it is not excreted in urine, and the unchanged drug represents a relatively minor proportion of total radioactivity excreted following the administration of [14C]-primaquine to a panel of human subjects (Mihaly et al, 1985b). Malaria infection alters the pharmacokinetics and metabolism of a number of drugs in animals (Alvares et al, 1984, Mansor et al, 1990 and in man (White et al, 1982 (Mansor et al, 1991). An increased plasma binding would be expected to result in increased total plasma concentrations of primaquine but not necessarily any increase in free drug concentrations.…”

Population Pharmacokinetic and Pharmacodynamic Properties of Intramuscular Quinine in Tanzanian Children with Severe Falciparum Malaria

“…Peak total plasma concentrations tend to increase during the treatment of severe malaria until clinical resolution (17), so it is possible that some patients might have experienced potentially toxic quinine concentrations later in their treatment course. The levels of quinine associated with toxicity in severe malaria are not well established, since toxicity derives from the free quinine fraction, which depends on the levels of plasma proteins, predominantly AGP, which vary substantially (18,19). The pharmacokinetic study reported previously by van Hensbroek et al showed that young children could be more prone to quinine toxicity, as evidenced by a slight prolongation of the QRS interval on the electrocardiogram (intraventricular conduction delay), although this was not related to plasma quinine concentrations (10).…”

“…The pharmacokinetic properties of quinine are affected by the severity of infection as well as age (5,10). The apparent volume of distribution (V/F) and elimination clearance (CL/F) values are significantly reduced in proportion to increased disease severity (5,17), partly because of increased quinine binding to plasma proteins, mainly alpha 1-acid glycoprotein (AGP) (18,19). Quinine clearance is also altered by some drug interactions (20).…”

Assessment of inflammatory and immunity proteins during falciparum malaria infection in children of Côte d’Ivoire

“…At the biochemical level, according to Mansor et al (1991) and Hurt et al (1994), the significant increase of CRP and AGP concentrations indicative of inflammatory reaction during malaria, Thus, the CRP is secreted in order to fight against Plasmodium falciparum invasion (Volankis, 2001) . It binds damaged host cells including erythrocyte infected by Plasmodium falciparum, resulting in their clearance by both humoral and cellular immune mechanism (Ansar et al, 2006).…”