Population pharmacokinetics of intramuscular quinine in children with severe malaria.
We present the first population pharmacokinetic analysis of quinine in patients with Plasmodium falciparum malaria. Ghanaian children (n = 120; aged 12 months to 10 years) with severe malaria received an intramuscular loading dose of quinine dihydrochloride (20 mg/kg of body weight). A two-compartment model with first-order absorption and elimination gave post hoc estimates for pharmacokinetic parameters that were consistent with those derived from non-population pharmacokinetic studies (clearance [CL] = 0.05 liter/h/kg of body weight; volume of distribution in the central compartment [V(1)] = 0.65 liter/kg; volume of distribution at steady state = 1.41 liter/kg; half-life at beta phase = 19.9 h). There were no covariates (including age, gender, acidemia, anemia, coma, parasitemia, or anticonvulsant use) that explained interpatient variability in weight-normalized CL and V(1). Intramuscular quinine was associated with minor, local toxicity in some patients (13 of 108; 12%), and 11 patients (10%) experienced one or more episodes of postadmission hypoglycemia. A loading dose of intramuscular quinine results in predictable population pharmacokinetic profiles in children with severe malaria and may be preferred to the intravenous route of administration in some circumstances.
Krishna
S
S
Department of Infectious Diseases, St. George's Hospital Medical School, Cranmer Terrace, London SW17 ORE, United Kingdom. s.krishna@shgms.ac.uk
Nagaraja
N V
NV
Planche
T
T
Agbenyega
T
T
Bedo-Addo
G
G
Ansong
D
D
Owusu-Ofori
A
A
Shroads
A L
AL
Henderson
G
G
Hutson
A
A
Derendorf
H
H
Stacpoole
P W
PW
D000140:Acidosis, Lactic / Q000209:etiology; D000818:Animals; D000962:Antimalarials / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003999:Dichloroacetic Acid / Q000494:pharmacology*; D005260:Female; D005869:Ghana; D006207:Half-Life; D006439:Hemodynamics; D006801:Humans; D007223:Infant; D007273:Injections, Intramuscular; D016778:Malaria, Falciparum / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D010963:Plasmodium falciparum; D011803:Quinine / Q000493:pharmacokinetics* / Q000627:therapeutic use
D000962:Antimalarials; D003999:Dichloroacetic Acid; D011803:Quinine