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Efficacy and pharmacokinetics of a new intrarectal quinine formulation in children with Plasmodium falciparum malaria
Author(s) -
BARENNES H.,
PUSSARD E.,
MAHAMAN SANI A.,
CLAVIER F.,
KAHIATANI F.,
GRANIC G.,
HENZEL D.,
RAVINET L.,
VERDIER F.
Publication year - 1996
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.1365-2125.1996.03246.x
Subject(s) - medicine , tolerability , plasmodium falciparum , quinine , intramuscular injection , pharmacokinetics , malaria , anesthesia , gastroenterology , adverse effect , pharmacology , immunology
1 Three groups of seven children aged 2–14 years with acute uncomplicated Plasmodium falciparum malaria received 12.8 mg kg −1 quinine gluconate by the intrarectal route (new cream formulation) or 8 mg kg −1 Quinimax (a Cinchona alkaloid combination) by the intramuscular or intravenous (4 h infusion) route every 8 h for 3 days. Clinical and parasitological status was similar in the three groups at enrolment. 2 At 36 h, body temperature of all children of the three groups was returned to normal and remained so until day 7. 3 The decrease in parasitaemia did not differ between the three groups and the time required for a 50% fall in parasitaemia relative to baseline was 12.3±5.4, 18.2±6.1 and 14.5±4.2 h in the intrarectal, intramuscular and intravenous treatment groups, respectively. Parasitaemia expressed as a percentage of initial values was not significantly different in the three groups after 48 h of treatment (7.4±16.0, 4.1±4.2 and 2.2±3.8% in the intrarectal, intramuscular and intravenous treatment groups, respectively). All the patients were aparasitaemic by day 7. 4 The tolerability of the three treatments was good; in particular, no rectal irritation was reported with the cream formulation. 5 The t max occurred later after intrarectal (4.1±2.4 h) and intravenous infusion (3.8±0.5 h) than after intramuscular injection (1.6±1.3 h) ( P =0.02). C max was lower with the intrarectal (3.0±1.0 mg l −1 ) and intramuscular routes (3.2±0.7 mg l −1 ) than with the intravenous route (5.1±1.4 mg l −1 ) ( P =0.003). Areas under the curve (AUC(0, 8 h)) were smaller with the intrarectal (17.0±7 mg l −1 h) and intramuscular routes (19.4±4.8 mg l −1 h) than with the intravenous route (27.8±8.2 mg l −1 h) ( P =0.02). The approximate bioavailability of intrarectal quinine from 0 to 8 h was 36% vs intravenous quinine and 51% vs intramuscular quinine. 6 The good tolerability and efficacy of this new intrarectal quinine formulation outweigh its low approximate bioavailability. This new approach might thus be a safe and effective alternative to intramuscular quinine injection for the treatment of children with acute uncomplicated Plasmodium falciparum malaria in the field.