Dose-Dependent Resorption of Quinine after Intrarectal Administration to Children with Moderate Plasmodium falciparum Malaria

Abstract

The pharmacokinetics of increasing doses of an intrarectal Cinchona alkaloid combination containing 96.1% quinine, 2.5% quinidine, 0.68% cinchonine, and 0.67% cinchonidine (Quinimax) was compared to that of parenteral regimens in 60 children with moderate malaria. Quinine exhibited a nonlinear pharmacokinetics, suggesting a saturation of rectal resorption. When early rejections appeared, blood quinine concentrations decreased by 30 to 50% and were restored by an immediate half-dose administration of the drug. Rectal administration of doses of 16 or 20 mg/kg of body weight led to concentration-time profiles in blood similar to those of parenteral regimens and could be an early treatment of childhood malaria.

Taste-masked quinine pamoate tablets for treatment of children with uncomplicated Plasmodium falciparum malaria

“…The percentage of children without an episode of fever increased with the duration of treatment and is in accordance with other studies where quinine was used to treat uncomplicated P. falciparum malaria in children (at 72 h all children were apyretic) (Pussard et al, 2004;Le Jouan et al, 2005).…”

“…However, the specific design of the quinine pamoate tablets offers technological advantages as the entire dose range for children up to 20 kg is covered with a single dosage form, whereas body weight adapted dosing by means of the pellets required that the pellets were packed into capsules of different sizes (Kayumba et al, 2008). Following treatment of children with 8 mg/kg quinine three times a day for 7 days similar plasma concentrations were also reported by different authors (Pussard et al, 2004;Le Jouan et al, 2005).…”

“…Moreover, quinine has revealed difficulties when administered via alternative routes: risk of limb paralysis following intramuscular injection (White and Krishna, 1989), poor availability when rectally administered with the eventual loss of medicine by expelling from the rectum (Pussard et al, 2004), and limited availability of appropriate equipment and trained staff required for perfusion of quinine at basic health centers in low and middleincome countries. Therefore, oral administration of quinine should be preferred on condition that the problem of bad taste is overcome.…”

Rectal versus Intravenous Quinine for the Treatment of Childhood Cerebral Malaria in Kampala, Uganda: A Randomized, Double-Blind Clinical Trial

“…This could be attributed to the use of the cannula syringe. This was particularly important, because early expulsion during the first hour after rectal administration has been revealed to decrease the blood quinine concentration by 50%, although immediate administration of one-half of the dose is shown to restore an effective blood concentration-to-time profile [9].…”

“…Each administration was followed by firm compression of the buttocks for 5 min to avoid early expulsion; if the drug was expelled within 30 min, one-half of the dose was readministered. This dosage was revealed by previous pharmacokinetic studies to be the optimal regimen leading to predictable, safe, and effective blood quinine concentrations [9]. These patients also received a 5% dextrose drip (20 mL/kg) without study drug every 8 h as a placebo.…”