Single dose disposition of chloroquine in kwashiorkor and normal children‐evidence for decreased absorption in kwashiorkor.

Walker, O; Dawodu, AH; Salako, L.A.; Alván, Gunnar; Johnson, Austin

doi:10.1111/j.1365-2125.1987.tb03077.x

Cited by 36 publications

(34 citation statements)

References 17 publications

(18 reference statements)

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“…A similar finding of slower absorption has been reported for chloroquine (Walker et al, 1987). Intestinal malabsorption is a feature of kwashiorkor (Scrimshaw & Behar, 1965;Dossetor & Whittle, 1975), its morphological basis being atrophy of the intestinal mucosa and smooth muscle (Stanfield et al, 1965).…”

Section: Discussionsupporting

confidence: 71%

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Pharmacokinetics of quinine in African children suffering from kwashiorkor.

Salako

Sowunmi

Akinbami

1989

Brit J Clinical Pharma

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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.

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Section: Discussionsupporting

confidence: 71%

“…In a previous study we provided evidence for reduced absorption of chloroquine in kwashiorkor (Walker et al, 1987). In the present study we have compared the pharmacokinetics of quinine after a single oral dose in children with kwashiorkor and in normal healthy children.…”

Section: Introductionmentioning

confidence: 89%

Pharmacokinetics of quinine in African children suffering from kwashiorkor.

Salako

Sowunmi

Akinbami

1989

Brit J Clinical Pharma

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“…Altered pharmacokinetics of SP in malnourished children also could play a role by causing, e.g., increased clearance, reduced drug concentrations, and reduced halflife, as has been shown for quinine (33). Likewise, oral chloroquine treatment has been reported to be associated with reduced peak and overall drug concentrations in children with kwashiorkor, suggesting decreased bioavailability (35). If the pharmacokinetic properties of SP were altered in malnourished children (and related to the reduced efficacy of IPTi), such influence would be expected to be pronounced.…”

mentioning

confidence: 99%

“…Malnutrition among infants is shamefully frequent in many parts of Africa and has been shown to affect antimalarial treatment responses, drug absorption, and immune responses, among others (13,14,22,27,33,35,39). Thus, it is appropriate to hypothesize that nutritional status influences the effect of IPTi.…”

mentioning

confidence: 99%

Reduced Efficacy of Intermittent Preventive Treatment of Malaria in Malnourished Children

Dietz

Zanger

Reither

et al. 2009

Antimicrob Agents Chemother

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Intermittent preventive treatment in infants with sulfadoxine-pyrimethamine (IPTi-SP) reduces malaria episodes by 20 to 59% across Africa. This protective efficacy, however, may be affected by the high frequency of malnutrition in African infants. We analyzed the impact of malnutrition as defined by anthropometry on the incidence of malaria and on the protective efficacy of IPTi in a cohort of 1,200 children in northern Ghana, where malaria is hyperendemic. These children received IPTi-SP or placebo at 3, 9, and 15 months of age and were monitored until 24 months of age. Malnutrition was present in 32, 40, and 50% of children at ages 3, 9, and 15 months, respectively. It was associated with increased risks of severe anemia and death but not an increased risk of malaria. Although malaria slightly contributed to chronic malnutrition, IPTi did not substantially improve child growth. Importantly, the protective efficacies of IPTi in malnourished children were roughly half or even less of those observed in nonmalnourished children. In the first year of life, IPTi reduced the incidence of malaria to a significantly lesser extent in infants who received both doses in a malnourished condition (25%; 95% confidence interval [CI], ؊7 to 48%) compared to that of nonmalnourished children (46%; 95% CI, 30 to 58%; P ‫؍‬ 0.049). Moreover, in contrast to nutritionally advantaged children, the rate of severe malaria appeared to be increased in malnourished children who took IPTi. IPTi might exhibit reduced efficacy in regions of abundant malnutrition. Concomitant nutrition programs may be needed in these places to achieve the desired impact.Intermittent preventive treatment in infants (IPTi) with sulfadoxine-pyrimethamine (SP) appears to be a promising tool of malaria control in young children. The initial IPTi trial in Tanzania reported a protective efficacy (PE) against uncomplicated malaria in infancy of 59% and some degree of protection persisting into the second year of life (28, 29). In subsequent studies at sites of differing endemicity in sub-Saharan Africa, protection in infancy was confirmed; however, the PEs were lower, at 20 to 33% (5,12,15,17,23). We have reported previously that in Tamale, northern Ghana, IPTi reduced the incidence of asymptomatic parasitemia, uncomplicated malaria, and severe anemia from 3 to 24 months of age by 29, 17, and 15%, respectively. These effects were greatest in the first year of life and less pronounced in the second (23).As in many regions of Africa, malnutrition is abundant in northern Ghana, reaching prevalences as high as 50% in preschool children, depending on seasonality and food availability (32 and http://www.who.int/nutgrowthdb/database/countries /nchs_reference/gha.pdf). Malnutrition causes relative immunosuppression, and repeated or chronic infections may contribute to poor nutritional status (27). However, the effect of malnutrition on malaria is less clear cut than would be expected: protein-energy malnutrition has been associated with greater malaria morbidity and mortalit...

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“…21,22 Given the fact that the metabolism of ACT drugs has not been studied in these children, they may be at risk of ACT drug toxicity; therefore, these children need to be studied as a separate cohort.…”

Section: Setting Of the Studymentioning

confidence: 99%