Differences in the binding of quinine and quinidine to plasma proteins.

Abstract

1 Little is known about the comparative plasma protein binding of the antimalarial agents quinine (QN) and its isomer quinidine (QD). We have examined the in vitro binding of QN and QD to albumin, a,-acid glycoprotein, normal human plasma, and maternal and foetal umbilical cord plasma. 2 QN was more avidly bound than QD, and binding of both drugs was substantially higher to a,-acid glycoprotein than to albumin, indicating that ot,-acid glycoprotein is the more important binding protein.3 Protein and drug concentration dependent binding was evident for both QN and QD. The unbound fraction of both drugs fell with increasing albumin (10 to 60 g 1-1) and a,r-acid glycoprotein (0.5 to 2.0 g 1-1) concentration, and there was a marked increase in unbound fraction of QN (6 to 19%) and QD (13 to 36%) in human plasma when drug concentrations were increased over the antimalarial therapeutic range (0.5 to 10 mg 1-1). 4 In human volunteer plasma, the unbound fractions of QN and QD were 7.5 ± 2.2% and 12.3 ± 2.3% respectively, whilst the unbound fractions for both drugs were significantly higher in maternal plasma (QN = 13.0 ± 5.4%, QD= 18.3 ± 2.5%) and significantly higher still in foetal umbilical cord plasma (QN = 25.7 10%, QD = 35 ± 5.3%).

Alpha 1‐acid glycoprotein (orosomucoid) and plasma protein binding of quinine in falciparum malaria.

“…This is supported by the observations in the present study; there was no relationship between serum albumin concentration and quinine binding, but a significant log linear correlation between AAG concentration and the fraction of quinine bound. However we and others (Mihaly et al, 1987) have found that plasma protein binding of quinidine (circa 70-80%) is significantly lower than quinine plasma protein binding (85-95%), and AAG affinity is correspondingly less, and so as with other isomers, findings concerning one diastereoisomer cannot necessarily be extrapolated to the other. In this study the Hill plot gave mean (s.e.…”

Pharmacokinetics of quinine in African children suffering from kwashiorkor.

“…This may be compounded further by differences in distribution and plasma protein binding which have not been assessed in this study. It is known that quinine is highly protein bound (92%) and that the percentage binding varies directly with plasma protein concentration (Mihaly et al, 1987). Patients with kwashiorkor and malaria treated with quinine should be carefully monitored to see whether there are any clinical correlates with the pharmacokinetic changes.…”

In Vitro Synergy and Enhanced Murine Brain Penetration of Saquinavir Coadministered with Mefloquine

“…This has important implications since, theoretically, the shift from high-affinity to lowaffinity binding may influence the ability of compounds to cross biological membranes. Indeed, differences in orosomucoid binding have been shown to alter hepatic extraction ratio of quinidine (Mansor et al, 1991), a drug that is bound to both orosomucoid and albumin (Mihaly et al, 1987).…”