Titre : Médecine tropicale
Auteur : Institut de médecine tropicale du Service de santé des armées (Marseille). Auteur du texte
Éditeur : Médecine tropicale (Marseille)
Date d'édition : 1986-10-01
Notice du catalogue : http://catalogue.bnf.fr/ark:/12148/cb34348866b
Type : texte texte
Type : publication en série imprimée publication en série imprimée
Langue : français
Format : Nombre total de vues : 22136 Nombre total de vues : 22136
Description : 01 octobre 1986 01 octobre 1986
Description : 1986/10/01 (N4,VOL46)-1986/12/31. 1986/10/01 (N4,VOL46)-1986/12/31.
Droits : Consultable en ligne
Identifiant : ark:/12148/bpt6k6437928b
Source : Bibliothèque de l'IRBA - antenne de Marseille, 2012-265383
Conservation numérique : Bibliothèque nationale de France
Date de mise en ligne : 20/05/2013
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- SOMMAIRE VOLUME 46 N° 4
- CONTENTS
- TABLE DES MATIERES
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- .......... Page(s) .......... 349
- La fièvre typhoïde chez l'enfant en zone rurale tunisienne. Etude épidémiologique et clinique (M.T.).......... Page(s) .......... 349
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- TABLE DES AUTEURS
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MEDECINE TROPICALE
VOLUME 46 - N° 4 OCTOBRE-DECEMBRE 1986
MEMOIRES ET TRAVAUX ORIGINAUX
PHARMACOCINETIQUE DES ANTIPALUDEENS :
QUININE ET MEFLOQUINE, HALOFANTRINE, QINGHAOSU, AMINO-4-QUINOLEINES
par
F. VERDIER (1), E. PUSSARD (1), M.C. BLAYO (1)
SUMMARY
PHARMACOKINETICS OF ANTIMALARIAL DRUGS :
QUININE AND MEFLOQUINE,
HALOFANTRINE, QINGHAOSU, 4-AMINO-QUINOLINES.
The development of new sensitive and specific assays
(HPLC) have enabled the pharmacokinetics of antimalarial
drugs to be studied. Parameters such as half-life, distribution
volume, clearance and bioavailability, are defined.
In healthy subjects, quinine is rapidly eliminated (t 1/2 :
6-12 h). Hepatic biotransformation accounts for approxima-
tely 80% of its total clearance. In malaria, the pharmaco-
kinetic properties of quinine (decrease in the apparent volume
of distribution, prolongation of the t B , reduction in syste-
rnic clearance), are altered in proportion to the severity of
infection. Red cell concentrations and plasma binding are
tncreased. Parenteral quinine should be given by slow intra-
yenous infusion and a loading dose is recommanded in severe
infections.
Chloroquine (t 1/2 a : 6-50 days) and mefloquine (t 1/2 ® :
6-33 days) have extensive tissue distribution and prolonged
acttVtty after a single dose. Both drugs are concentrated in
erythrocytes and are bound considerably to plasma proteins.
Amodiaquine is not found in the blood after oral adminis-
tratIon. Hepatic biotransformation accounts for almost ail
otally administered drug. Its antiplasmodial activity is thus
almost entirely due to monodesethylamodiaquine, the main
rnetabolite. In healthy subjects, the t B of this metabolite
is 9 to 18 days in plasma. Amodiaquine is concentrated
in erythrocytes. The protein binding of this drug has not
been studied to date. For prophylaxis, it has been sug-
gested that the dosage of 10 mg/kg/wk should be spread
over the week (3.5 mg/kg every other day, or 1.5 every day).
Halofantrine has an elimination half-life of between 1.3
and 6.6 days. This drug has been suggested as a single-dose
treatment.
No pharmacokinetic studies of qinghaosu have been repor-
ted in humans. In rabbits, the elimination half-life in plasma
was found to be 40 min. Although rapidly eliminated, this
drug appears to be highly effective.
More information is required on the pharmacokinetics of
these drugs in malaria, during pregnancy, in children and in
renal and hepatic failure.
La pharmacocinétique a pour objet l'étude descrip-
tive et quantitative du devenir d'un médicament dans
l'organisme auquel il est administré (23) : ce qui la
définit comme la description mathématique des pro-
cessus d'absorption, de distribution, de métabolisme
et d'excrétion (8). Il nous parait donc indispensable,
au début de cette revue générale, de définir les diffé-
rents paramètres utilisés pour caractériser la pharma-
cocinétique d'un médicament.
(1) I.N.S.E.R.M. U 13, Institut de médecine et d'épidémiologie africaines, hôpital Claude-Bernard, 10, avenue de la Porte-d'Au-
bervilliers, 75019 Paris.
MEDECINE TROPICALE - Volume 46 - N° 4 - Octobre-Décembre 1986
VOLUME 46 - N° 4 OCTOBRE-DECEMBRE 1986
MEMOIRES ET TRAVAUX ORIGINAUX
PHARMACOCINETIQUE DES ANTIPALUDEENS :
QUININE ET MEFLOQUINE, HALOFANTRINE, QINGHAOSU, AMINO-4-QUINOLEINES
par
F. VERDIER (1), E. PUSSARD (1), M.C. BLAYO (1)
SUMMARY
PHARMACOKINETICS OF ANTIMALARIAL DRUGS :
QUININE AND MEFLOQUINE,
HALOFANTRINE, QINGHAOSU, 4-AMINO-QUINOLINES.
The development of new sensitive and specific assays
(HPLC) have enabled the pharmacokinetics of antimalarial
drugs to be studied. Parameters such as half-life, distribution
volume, clearance and bioavailability, are defined.
In healthy subjects, quinine is rapidly eliminated (t 1/2 :
6-12 h). Hepatic biotransformation accounts for approxima-
tely 80% of its total clearance. In malaria, the pharmaco-
kinetic properties of quinine (decrease in the apparent volume
of distribution, prolongation of the t B , reduction in syste-
rnic clearance), are altered in proportion to the severity of
infection. Red cell concentrations and plasma binding are
tncreased. Parenteral quinine should be given by slow intra-
yenous infusion and a loading dose is recommanded in severe
infections.
Chloroquine (t 1/2 a : 6-50 days) and mefloquine (t 1/2 ® :
6-33 days) have extensive tissue distribution and prolonged
acttVtty after a single dose. Both drugs are concentrated in
erythrocytes and are bound considerably to plasma proteins.
Amodiaquine is not found in the blood after oral adminis-
tratIon. Hepatic biotransformation accounts for almost ail
otally administered drug. Its antiplasmodial activity is thus
almost entirely due to monodesethylamodiaquine, the main
rnetabolite. In healthy subjects, the t B of this metabolite
is 9 to 18 days in plasma. Amodiaquine is concentrated
in erythrocytes. The protein binding of this drug has not
been studied to date. For prophylaxis, it has been sug-
gested that the dosage of 10 mg/kg/wk should be spread
over the week (3.5 mg/kg every other day, or 1.5 every day).
Halofantrine has an elimination half-life of between 1.3
and 6.6 days. This drug has been suggested as a single-dose
treatment.
No pharmacokinetic studies of qinghaosu have been repor-
ted in humans. In rabbits, the elimination half-life in plasma
was found to be 40 min. Although rapidly eliminated, this
drug appears to be highly effective.
More information is required on the pharmacokinetics of
these drugs in malaria, during pregnancy, in children and in
renal and hepatic failure.
La pharmacocinétique a pour objet l'étude descrip-
tive et quantitative du devenir d'un médicament dans
l'organisme auquel il est administré (23) : ce qui la
définit comme la description mathématique des pro-
cessus d'absorption, de distribution, de métabolisme
et d'excrétion (8). Il nous parait donc indispensable,
au début de cette revue générale, de définir les diffé-
rents paramètres utilisés pour caractériser la pharma-
cocinétique d'un médicament.
(1) I.N.S.E.R.M. U 13, Institut de médecine et d'épidémiologie africaines, hôpital Claude-Bernard, 10, avenue de la Porte-d'Au-
bervilliers, 75019 Paris.
MEDECINE TROPICALE - Volume 46 - N° 4 - Octobre-Décembre 1986
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