PHARMACOKINETICS AND DISPOSITION Intrarectal pharmacokinetics of two formulations of quinine in children with falciparum malaria Received: 18 March 2002 / Accepted: 23 November 2002 / Published online: 29 January 2003 Ó Springer-Verlag 2003 Abstract Objective: To compare the intrarectal bioavai- labilities of two parenteral formulations of quinine most available in French- (Cinchona alkaloid mixture) and English (hydrochloride salt) -speaking areas of Africa. Methods: The pharmacokinetics of quinine was investi- gated in four groups of 12 children with acute Plasmo- dium falciparum malaria receiving 8 mg/kg quinine base every 8 h either as hydrochloride salt or Cinchona alkaloid mixture by a slow 4-h intravenous infusion or intrarectal administration. Body temperature and para- sitaemia were monitored, and blood quinine concentra- tions were measured by means of high-performance liquid chromatography. Results: At 72 h, all the children were aparasitaemic and apyretic. Quinine C max values were higher after intravenous infusion of the hydro- chloride salt and Cinchona alkaloid mixture (6.9±1.9 lg/ml and 5.2±1.3 lg/ml) than after intra- rectal administration (3.5±1.4 lg/ml and 3.1±1.6 lg/ ml), but t max values were similar (3.6±1.5, 4.2±1.0, 4.0±1.9, and 4.7±2.0 h, respectively). Intrarectal rela- tive bioavailabilities of hydrochloride salt solution (57%) and Cinchona alkaloid mixture (62%) were sim- ilar. Conclusion: 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. Keywords Quinine hydrochloride salt Æ Cinchona alkaloid mixture Æ Intrarectal administration Æ Pharmacokinetics Æ Childhood malaria Introduction Quinine, which is classically reserved for the treatment of severe malaria, is in fact widely used in most African countries as first or second line treatment of uncompli- cated malaria because of its high efficacy and relatively low cost. In French-speaking areas of Africa, quinine is mainly available as a Cinchona alkaloid mixture con- taining more than 95% quinine, associated with low concentrations of quinidine, cinchonine and cinchoni- dine. Quinidine and cinchonine have been shown to be more effective than quinine in vitro and in vivo [1, 2]. When used in a combination of one-third quinine, qui- nidine and cinchonine, interactions between drugs were suggested by the higher plasma concentrations than when given alone [3]. In Niger, we have demonstrated that intrarectal administration of the Cinchona alkaloid mixture in children could be an alternative to intra- muscular injections, which are often associated with neurological and infectious complications. Moreover, it replaces the oral route in the presence of vomiting, nausea or confusion, and is an early treatment of childhood malaria at the peripheral healthcare level [4]. In English-speaking areas of Africa, the Cinchona al- kaloid mixture is not available, and the hydrochloride salt is the most used formulation. Its efficacy after intrarectal administration was never evaluated. We therefore compared these two formulations of quinine in terms of blood profiles and relative bio- availability after intrarectal and intravenous adminis- tration in children with falciparum malaria. Eur J Clin Pharmacol (2003) 58: 649–652 DOI 10.1007/s00228-002-0546-2 H. Barennes Æ H. Sterlingot Æ N. Nagot Æ H. Meda M. Kabore´ Æ M. Sanou Æ B. Nacro Æ P. Boure´e E. Pussard H. Barennes Æ N. Nagot Æ H. Meda Centre Muraz, Bobo Dioulasso, Burkina Faso H. Sterlingot Æ P. Boure´e Æ E. Pussard (&) Services de Pharmacologie et des Parasitologie, Hoˆpital de Biceˆtre, 78 rue du Ge´ne´ral Leclerc, 94275 , Le Kremlin-Biceˆtre, France E-mail: eric.pussard@bct.ap-hop-paris.fr Tel.: +33-1-45213592 Fax: +33-1-45213591 M. Sanou Æ B. Nacro Service de Pe´diatrie, Hoˆpital Sanou Souro, Bobo Dioulasso, Burkina Faso