Pharmacokinetics of quinine in African children suffering from kwashiorkor.

Abstract

The pharmacokinetics of quinine were studied in seven normal African children and in six African children suffering from kwashiorkor, after an oral dose of 10 mg kg-1 of quinine hydrochloride. The two groups were similar in age but the children with kwashiorkor weighed significantly less than the control children (P < 0.001). The children with kwashiorkor further differed from the control children in having significantly lower packed cell volume (P < 0.001), total plasma protein and plasma albumin (P < 0.001), and higher serum SGOT (P < 0.05). The apparent absorption half-life was significantly longer in kwashiorkor than in controls (P < 0.05). Similarly, the Cmax was significantly lower (P < 0.01) in kwashiorkor than in controls. Quinine was eliminated more slowly in children with kwashiorkor, the elimination half-life being significantly longer (P < 0.001) and the oral clearance significantly less (P < 0.001) than in controls. It is concluded that kwashiorkor significantly affects the pharmacokinetics of quinine, and that the effect may be due to the pathological changes in the intestine and liver in this condition.

A systematic review of pharmacokinetics studies in children with protein-energy malnutrition

“…The total clearance of five drugs was significantly decreased with a correspondingly increased half-life [18,26,40,[42][43][44]. The total clearance of quinine was significantly decreased in two studies involving poorly categorised malnourished children [51] and kwashiorkor [30], but significantly increased in another study involving children with all categories of PEM except kwashiorkor [21]. Similarly, in one study, the total clearance of chloramphenicol was either significantly decreased in kwashiorkor or unaffected in marasmus and marasmic-kwashiorkor [45].…”

“…In addition, contrasting results were also documented for quinine. The extent of absorption of oral quinine was increased [30] whereas the extent of IM absorption was not significantly affected [21].…”

“…Only two antimalarials; chloroquine [25,39] and quinine [21,30,51], were studied. Resistance to chloroquine has necessitated the use of artemesinin based combined therapy as first line treatment for malaria in sub-Saharan African countries [62] and the WHO has recommended artemether and lumefantrine combination in malaria endemic developing nations [63].…”

“…One to 17 blood samples were collected from individual children. Table 1 shows the effect of PEM on absorption of 18 drugs [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32]. The extent of absorption of most of the drugs (10) was not significantly affected.…”

Prise en charge du paludisme pédiatrique: rôle des interventions nutritionnelles

“…L'un de ces travaux a suggéré la nécessité d'une réduction de 12 à 8 heures de l'intervalle d'administration de la quinine par voie intramusculaire [82] , mais deux autres études ayant respectivement porté sur la quinine orale et intraveineuse ont observé plusieurs différences entre les paramètres pharmacodynamiques de ce produit chez des enfants présentant ou non un paludisme, dans les deux cas en association à une malnutrition globale sévère [83,84] . Les auteurs des deux études ont cependant conclu qu'aucune modification de la posologie n'était né-cessaire.…”