Re: INDICES> Quinine levels and kinetics

[Beverley Snell <bev@burnet.edu.au>]

In response to Dr Marc Blockman's query, Dr James Beeson,
<beeson@wehi.edu.au>  Division of Infection and Immunity, The Walter and
Eliza Hall Institute of Medical Research in Melbourne,  Australia,
provided the following information.

A good starting point would be the 2nd Edition "Severe and Complicated
Malaria" from WHO, also published as a supplement to the Trans R Soc Trop
Med Hyg Vol 84 (suppl 2) 1990. Many places in developing countries have
this as a reference manual and it gives an overview of antimalarial
pharmacokinetics.

For more specific information on plasma levels of quinine and protein
binding:
Silamut et al 1985 Am J Trop Med Hyg 34(4):681-6
Mihaly et al 1987 Brit J Pharmacol 24(6):769-74

Qunine predominantly binds to alpha 1 acidic glycoprotein (and less so to
albumin). As it is an acute phase protein, the concentration of bound
quinine increases in severe malaria, and the unbound or free concentration
may or may not fall. Typically, the total plasma concentration of quinine
is higher in malaria infected individuals, especially in severe malaria,
in part because of increased plasma protein binding.

Quoted proportion of free quinine in normal individuals was 7.5% of the
total plasma concentration in one study, and 10-11% in another, dropping
to 7.2% in cerebral malaria. Bear in mind also that the volume of
distribution of quinine is reduced (by up to 60%) in malaria infected
individuals, especially those with CM, which may also increase plasma
concentration, and indicates that free quinine levels may not necessarily
drop in severe or uncomplicated malaria.

Beverley Snell

Beverley Snell
Public Health Pharmacist
International Health Unit, Macfarlane Burnet Centre for Medical Research
P O Box 254 Fairfield Australia 3078
Telephone 613 9282 2115 / 9282 2275
Fax 613 9482 3123
email <bev@burnet.edu.au>



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