SHORT REPORT: LACK OF PREDICTION OF AMODIAQUINE EFFICACY IN TREATING PLASMODIUM FALCIPARUM MALARIA BY IN VITRO TESTS

AGNÉS AUBOUY Centre International de Recherches Médicales de Franceville, Unité de Parasitologie Médicale, Franceville, Gabon; Unité de Parasitologie, Institut de Médecine Tropicale du Service de Santé des Armées, le Pharo, Marseille Armées, France; Hôpital de Bakoumba, Bakoumba, Gabon; Hôpital Bichat-Claude Bernard, Laboratoire de Parasitologie, Paris, France; Institut de Recherche pour le Développement, Unité de Recherche 010 Mother and Child Health in the Tropics, Paris, France

Search for other papers by AGNÉS AUBOUY in
Current site
Google Scholar
PubMed
Close
,
JUSTICE MAYOMBO Centre International de Recherches Médicales de Franceville, Unité de Parasitologie Médicale, Franceville, Gabon; Unité de Parasitologie, Institut de Médecine Tropicale du Service de Santé des Armées, le Pharo, Marseille Armées, France; Hôpital de Bakoumba, Bakoumba, Gabon; Hôpital Bichat-Claude Bernard, Laboratoire de Parasitologie, Paris, France; Institut de Recherche pour le Développement, Unité de Recherche 010 Mother and Child Health in the Tropics, Paris, France

Search for other papers by JUSTICE MAYOMBO in
Current site
Google Scholar
PubMed
Close
,
ANNICK KEUNDJIAN Centre International de Recherches Médicales de Franceville, Unité de Parasitologie Médicale, Franceville, Gabon; Unité de Parasitologie, Institut de Médecine Tropicale du Service de Santé des Armées, le Pharo, Marseille Armées, France; Hôpital de Bakoumba, Bakoumba, Gabon; Hôpital Bichat-Claude Bernard, Laboratoire de Parasitologie, Paris, France; Institut de Recherche pour le Développement, Unité de Recherche 010 Mother and Child Health in the Tropics, Paris, France

Search for other papers by ANNICK KEUNDJIAN in
Current site
Google Scholar
PubMed
Close
,
MOHAMED BAKARY Centre International de Recherches Médicales de Franceville, Unité de Parasitologie Médicale, Franceville, Gabon; Unité de Parasitologie, Institut de Médecine Tropicale du Service de Santé des Armées, le Pharo, Marseille Armées, France; Hôpital de Bakoumba, Bakoumba, Gabon; Hôpital Bichat-Claude Bernard, Laboratoire de Parasitologie, Paris, France; Institut de Recherche pour le Développement, Unité de Recherche 010 Mother and Child Health in the Tropics, Paris, France

Search for other papers by MOHAMED BAKARY in
Current site
Google Scholar
PubMed
Close
,
JACQUES LE BRAS Centre International de Recherches Médicales de Franceville, Unité de Parasitologie Médicale, Franceville, Gabon; Unité de Parasitologie, Institut de Médecine Tropicale du Service de Santé des Armées, le Pharo, Marseille Armées, France; Hôpital de Bakoumba, Bakoumba, Gabon; Hôpital Bichat-Claude Bernard, Laboratoire de Parasitologie, Paris, France; Institut de Recherche pour le Développement, Unité de Recherche 010 Mother and Child Health in the Tropics, Paris, France

Search for other papers by JACQUES LE BRAS in
Current site
Google Scholar
PubMed
Close
, and
PHILIPPE DELORON Centre International de Recherches Médicales de Franceville, Unité de Parasitologie Médicale, Franceville, Gabon; Unité de Parasitologie, Institut de Médecine Tropicale du Service de Santé des Armées, le Pharo, Marseille Armées, France; Hôpital de Bakoumba, Bakoumba, Gabon; Hôpital Bichat-Claude Bernard, Laboratoire de Parasitologie, Paris, France; Institut de Recherche pour le Développement, Unité de Recherche 010 Mother and Child Health in the Tropics, Paris, France

Search for other papers by PHILIPPE DELORON in
Current site
Google Scholar
PubMed
Close
Restricted access

Amodiaquine (AQ) is currently a major candidate for new antimalarial combinations, although in vivo and in vitro tests have been rarely simultaneously investigated. The efficacy of AQ was assessed at the dose of 30 mg/kg in treating Plasmodium falciparum malaria attacks in 74 children from southeast Gabon, and the in vitro activity of monodesethylamodiaquine (MdAQ), the main metabolite of AQ, was measured against P. falciparum parasites isolated from these children. Treatment failures were observed in 40.5% of the children, while 5.4% of the isolates showed in vitro resistance to MdAQ. No relationship was observed between in vivo and in vitro susceptibility. The in vitro activities of MdAQ and chloroquine were correlated. The reasons for such disparities between in vivo and in vitro AQ activities are discussed and the issue of the validity of in vitro tests to measure AQ efficacy is raised.

Author Notes

Reprint requests: Philippe Deloron, Institut de Recherche pour le Développement, Unité de Recherche 010, Faculté de Pharmacie, 4 Avenue de l’Observatoire, 75006 Paris, France, Telephone: 33-1-53-73-96-22, Fax: 33-1-53-73-96-17, E-mail: Philippe.Deloron@ird.fr.
  • 1

    World Health Organization, 1996. Assessment of Therapeutic Efficacy of Antimalarial Drugs for Uncomplicated falciparum Malaria in Areas with Intense Transmission. Geneva: World Health Organization. WHO/MAL/96.1077.

    • PubMed
    • Export Citation
  • 2

    Le Bras J, Ringwald P, 1990. Situation de la chimiorésistance de Plasmodium falciparum en Afrique en 1989. Med Trop (Mars) 50 :11–16.

  • 3

    Aubouy A, Bakary M, Mbomat B, Makita JR, Keundjian A, Migot-Nabias F, Le Bras J, Deloron P, 2003. Combination of drug dosage and parasite genotyping data for a better assessment of amodiaquine and sulfadoxine-pyrimethamine efficacy to treat Plasmodium falciparum malaria in Gabonese children. Antimicrob Agents Chemother 47 :231–237.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    World Health Organization, 2002. Monitoring Antimalarial Drug Resistance. Geneva: World Health Organization. WHO/CDS/CSR/EPH/2002,17.

    • PubMed
    • Export Citation
  • 5

    Le Bras J, Deloron P, 1983. In vitro study of drug sensitivity of Plasmodium falciparum: evaluation of a new semi-micro test. Am J Trop Med Hyg 32 :447–451.

  • 6

    Le Bras J, Simon F, Ramanamirija JA, Calmel MB, Hatin I, Deloron P, Porte J, Marchais H, Clausse JL, Biaud JM, Sarrouy J, Guiguemde TR, Carme B, Charmot G, Coulaud JP, Coulanges P, 1987. Sensibilité de Plasmodium falciparum aux quinoléines et stratégies thérapeutiques: comparaison de la situation en Afrique et à Madagascar entre 1983 et 1986. Bull Soc Pathol Exot Filiales 80 :477–489.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Brasseur P, Agnamey P, Same Ekobo A, Samba G, Favennec L, Kouamouo J, 1995. Sensitivity of Plasmodium falciparum to amodiaquine and chloroquine in central Africa: a comparative study in vivo and in vitro. Trans R Soc Trop Med Hyg 89 :528–530.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Trenholme KR, Kum DE, Raiko AK, Gibson N, Narara A, Alpers MP, 1993. Resistance of Plasmodium falciparum to amodiaquine in Papua New Guinea. Trans R Soc Trop Med Hyg 87 :464–466.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Ringwald P, Keundjian A, Same Ekobo A, Basco LK, 2000. Chemoresistance of Plasmodium falciparum in the urban region of Yaounde, Cameroon. Part 2: Evaluation of the efficacy of amodiaquine and sulfadoxine-pyrimethamine combination in the treatment of uncomplicated Plasmodium falciparum malaria in Yaounde, Cameroon. Trop Med Int Health 5 :620–627.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Basco LK, Ndounga M, Keundjian A, Ringwald P, 2002. Molecular epidemiology of malaria in Cameroon. IX. Characteristics of recrudescent and persistent Plasmodium falciparum infections after chloroquine or amodiaquine treatment in children. Am J Trop Med Hyg 66 :117–123.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Hengy C, Garrigue G, Abissegue B, Ghogomu NA, Gazin P, Gelas H, Kouka-Bemba D, Le Bras J, Jambou R, 1989. Surveillance de la chimiosensibilité de Plasmodium falciparum à Yaoundé et ses environs (Cameroun). Etude in vivo et in vitro. Bull Soc Pathol Exot Filiales 82 :217–223.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Carme B, Moudzeo H, Mbitsi A, Ndounga M, Samba G, 1991. Stabilization of drug resistance (chloroquine and amodiaquine) of Plasmodium falciparum in semiimmune populations in the Congo. J Infect Dis 164 :437–438.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Sexton JD, Deloron P, Bugilimfura L, Ntilivamunda A, Neill M, 1988. Parasitologic and clinical efficacy of 25 and 50 mg/kg of chloroquine for treatment of Plasmodium falciparum malaria in Rwandan children. Am J Trop Med Hyg 38 :237–243.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Li XQ, Bjorkman A, Andersson TB, Ridderstrom M, Masimirembwa CM, 2002. Amodiaquine clearance and its metabolism to N-desethylamodiaquine is mediated by CYP2C8: a new high affinity and turnover enzyme-specific probe substrate. J Pharmacol Exp Ther 300 :399–407.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Ong CE, Coulter S, Birkett DJ, Bhasker B, Miners JO, 2000. The xenobiotic inhibitor profile of cytochrome P450 2C8. Br J Clin Pharmacol 50 :573–580.

  • 16

    Goldstein JA, 2001. Clinical relevance of genetic polymorphisms in the human CYP2C subfamily. Br J Clin Pharmacol 52 : 349–355.

  • 17

    Dai D, 2001. Allelic frequencies of human CYP2C8 and genetic linkage among different ethnic populations. FASEB J 15 :A575.

  • 18

    Churchill FC, Mount DL, Patchen LC, Bjorkman A, 1986. Isolation, characterization and standardization of a major metabolite of amodiaquine by chromatographic and spectroscopic methods. J Chromatogr 377 :307–318.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Mount DL, Patchen LC, Nguyen-Dinh P, Barber AM, Schwartz IK, Churchill FC, 1986. Sensitive analysis of blood for amodiaquine and three metabolites by high-performance liquid chromatography with electrochemical detection. J Chromatogr 383 :375–386.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    Pussard E, Verdier F, Faurisson F, Scherrmann JM, Le Bras J, Blayo MC, 1987. Disposition of monodesethylamodiaquine after a single oral dose of amodiaquine and three regimens for prophylaxis against Plasmodium falciparum malaria. Eur J Clin Pharmacol 33 :409–414.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Daubersies P, Sallenave-Sales S, Magne S, Trape JF, Contamin H, Fandeur T, Rogier C, Mercereau-Puijalon O, Druilhe P, 1996. Rapid turnover of Plasmodium falciparum populations in asymptomatic individuals living in a high transmission area. Am J Trop Med Hyg 54 :18–26.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Farnert A, Snounou G, Rooth I, Bjorkman A, 1997. Daily dynamics of Plasmodium falciparum subpopulations in asymptomatic children in a holoendemic area. Am J Trop Med Hyg 56 :538–547.

    • PubMed
    • Search Google Scholar
    • Export Citation
Past two years Past Year Past 30 Days
Abstract Views 43 42 2
Full Text Views 248 2 0
PDF Downloads 31 0 0
 
 
 
 
Affiliate Membership Banner
 
 
Research for Health Information Banner
 
 
CLOCKSS
 
 
 
Society Publishers Coalition Banner
Save