Intrarectal pharmacokinetics of two formulations of quinine in children with falciparum malaria

Hubert, Bernard; Sterlingot, Hélène; Nagot, Nicolas; Meda, Honoré A.; Kaboré, Moïse; Sanou, M.; Nacro, Boubacar; Bourée, Patrice; Pussard, Eric

doi:10.1007/s00228-002-0546-2

Cited by 16 publications

(29 citation statements)

References 8 publications

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“…The substitution of the hydrochloride for a gluconate salt and an increase in the pH value to 4.5 improve the local tolerance but may affect the extent of drug distribution (18). The kinetics profiles obtained after intravenous and intramuscular administrations are similar to those previously reported for hydrochloride salt (4,5). In contrast, after rectal administration of 8 mg/kg, the bioavailability of the gluconate form is higher than that previously observed with the more acidic formulations (3,5,6).…”

supporting

confidence: 83%

“…The kinetics profiles obtained after intravenous and intramuscular administrations are similar to those previously reported for hydrochloride salt (4,5). In contrast, after rectal administration of 8 mg/kg, the bioavailability of the gluconate form is higher than that previously observed with the more acidic formulations (3,5,6). The main mechanism of rectal absorption is a passive transport that depends mainly on the molecular weight, the lipophilicity, and the degree of ionization of molecules (19).…”

supporting

confidence: 80%

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

Pussard

Straczek

Kaboré

et al. 2004

Antimicrob Agents Chemother

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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.

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supporting

confidence: 83%

supporting

confidence: 80%

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

Pussard

Straczek

Kaboré

et al. 2004

Antimicrob Agents Chemother

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“…The formulation used in both treatment arms was Quinimax (Sanofi-Synthelabo Groupe), which contains 96% quinine, 2.5% quinidine, 0.68% cinchonine, and 0.67% cinchonidine. This was previously demonstrated to have a pharmacokinetic profile that is similar to that of quinine dihydrochloride [8]. For the intrarectal quinine group, the treatment nurse diluted a 500-mg vial of quinine with 13.5 mL of distilled water to obtain a concentration of 30 mg/mL.…”

Section: Participantsmentioning

confidence: 99%

“…Studies of the efficacy of intrarectal quinine in the treatment of cerebral malaria are limited. A few studies in Francophone Africa have reported good clinical efficacy and tolerance of intrarectal quinine [7][8][9][10][11]. Although these studies were randomized trials, they were not blinded and did not use the World Health Organization definition of cerebral malaria as selection criteria.…”

mentioning

confidence: 99%

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

Achan¹,

Byarugaba²,

Hubert³

et al. 2007

Clinical Infectious Diseases

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Background. Although artemesinin derivatives are promising for the treatment of severe Plasmodium falciparum malaria, intravenous quinine remains the most affordable treatment. However, administration of intravenous quinine is often not feasible in rural areas in Africa because of the lack of simple equipment or trained staff. We compared the efficacy and safety of intrarectal quinine with those of intravenous quinine in the treatment of childhood cerebral malaria.Methods. In a randomized, double-blind clinical trial at Mulago Hospital (Kampala, Uganda), Uganda's national referral hospital, we studied 110 children aged 6 months to 5 years who had cerebral malaria. Patients were randomized to receive either intrarectal or intravenous quinine. Main outcome measures included parasite clearance time, fever clearance time, coma recovery time, time to sit unsupported, time to begin oral intake, time until oral quinine was tolerated, and death.Results. Overall, there was no difference in the clinical and parasitological outcomes between the 2 groups (data are deviation, intrarectal quinine group vs. intravenous quinine group): coma recovery time, h versus mean ‫ע‬ standard 19.4 ‫ע‬ 18.1 h; fever clearance time, h versus h; and parasite clearance time, h versus 17.0 ‫ע‬ 12.1 26.7 ‫ע‬ 16.1 29.9 ‫ע‬ 18.1 43.2 ‫ע‬ 14.2 h. Mortality was similar in both groups; 4 of 56 patients in the intrarectal quinine group died, and 5 of 54 patients 41.9 ‫ע‬ 15.2 in the intravenous quinine group died (odds ratio, 1.3; 95% confidence interval, 0.3-5.2). Intrarectal quinine was well tolerated, and no major immediate adverse events occurred.Conclusions. Intrarectal quinine is efficacious and could be used as an alternative in the treatment of childhood cerebral malaria, especially in situations in which intravenous therapy is not feasible.

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Antimalarials

Smithson¹,

Guiguemde²,

Guy³

2010

Burger's Medicinal Chemistry and Drug Discovery

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While the treatment of malaria has until recently relied upon a small number of therapeutic agents with a few mechanisms of action, the past decade has seen a huge growth in the number of targets being addressed and new agents being pushed to the clinic. This chapter briefly reviews existing agents and close homologs in development and then carefully explores new targets and new chemotypes being developed.

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Intrarectal pharmacokinetics of two formulations of quinine in children with falciparum malaria

Abstract: Whatever the parenteral formulation of quinine, the blood concentration-time profiles of quinine were similar after intrarectal administration. Intrarectal administration of hydrochloride salt solution is a possible mode of quinine delivery in remote rural areas of Africa.

Cited by 16 publications

References 8 publications

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

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

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

Antimalarials

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