Taste-masked quinine sulphate pellets: bio-availability in adults and steady-state plasma concentrations in children with uncomplicated Plasmodium falciparum malaria.
BACKGROUND
Quinine sulphate (QS), like most other antimalarials, is in tablet form designed for adults. In children, treatment is based on breaking the tablets to adapt the dose to the child's bodyweight. However, poor breakability owing to the tablet design or the absence of a score line can lead to inaccurate dosage. Furthermore, QS is very bitter which reduces its acceptability to children. QS taste-masked pellets have been developed which offer more flexibility in adapting dosage to a child's weight.


OBJECTIVE
To evaluate the oral bio-availability of QS taste-masked pellets in healthy adult volunteers and to determine steady-state plasma concentrations in children aged <5 years with uncomplicated Plasmodium falciparum malaria.


METHODS
Healthy adult volunteers at Kigali University Hospital received a single dose of 600 mg QS as taste-masked pellets or as commercially available tablets. A total of 56 children <5 years with uncomplicated P. falciparum malaria were recruited among patients attending Butare University Hospital and nearby health centres and treated with QS taste-masked pellets, 10-12.5 mg/kg every 8 h for 7 days. Quinine steady-state plasma concentrations were assessed on the 4th day of treatment.


RESULTS
Following administration of taste-masked pellets to healthy adult volunteers, peak plasma concentration (C(max)) and area-under-the-curve (AUC) (C(max) 4.7 microg x ml(-1), AUC(0-24) 63.5 microg x h x ml(-1)) were significantly higher (p<0.05) than for tablets (C(max) 3.7 microg x ml(-1), AUC(0-24) 52.4 microg x h x ml(-1)), but still within the limits reported for quinine. The steady-state concentrations in children were in the therapeutic range for quinine. All the children recovered and completed the 14-day follow-up.


CONCLUSIONS
QS taste-masked pellets offered the possibility to easily adjust the dose to the bodyweight of the child and can be used as an alternative to dividing tablets.
Department of Pharmacy, National University of Rwanda, Butare, Rwanda.
P C
PC
Kayumba
M
M
Twagirumukiza
N
N
Huyghebaert
J D
JD
Ntawukuliryayo
L
L
van Bortel
C
C
Vervaet
J P
JP
Remon
D000284:Administration, Oral; D000328:Adult; D000962:Antimalarials / Q000008:administration & dosage / Q000097:blood*; D001682:Biological Availability; D001835:Body Weight; D002675:Child, Preschool; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000097:blood* / Q000188:drug therapy; D008297:Male; D011803:Quinine / Q000008:administration & dosage / Q000097:blood*; D013607:Tablets; D013649:Taste
D000962:Antimalarials; D013607:Tablets; D011803:Quinine