Bioequivalence evaluation of a fixed combination of chloroquine and proguanil in a capsule formulation versus a standard medication

To assess the bioequivalence between a test capsule with a fixed combination of chloroquine (CAS 54-05-7) and proguanil (CAS 500-92-5), and chloroquine and proguanil administered as separate tablets, an open two-sequence, two-period cross-over randomized study was performed in twelve healthy volunte...

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Bibliographic Details
Published inArzneimittel-Forschung Vol. 52; no. 5; p. 407
Main Authors Chaulet, Jean François, Nony, Patrice, Bévalot, Fabien, Girard, Pascal, Chabaud, Sylvie, Mounier, Cyril, Clair, Pascal, Boissel, Jean Pierre, Grelaud, Gilles
Format Journal Article
LanguageEnglish
Published Germany 01.01.2002
Subjects
Adult
Antimalarials - pharmacokinetics
Area Under Curve
Biological Availability
Chloroquine - pharmacokinetics
Cross-Over Studies
Drug Combinations
Erythrocytes - metabolism
Humans
Male
Proguanil - pharmacokinetics
Therapeutic Equivalency
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Summary:To assess the bioequivalence between a test capsule with a fixed combination of chloroquine (CAS 54-05-7) and proguanil (CAS 500-92-5), and chloroquine and proguanil administered as separate tablets, an open two-sequence, two-period cross-over randomized study was performed in twelve healthy volunteers who received a single oral dose of 100 mg chloroquine and 200 mg proguanil either in the form of one capsule or the reference tablets. Biological samples (plasma, whole blood and erythrocytes) were collected up to 43 days after drug administration. The parent drugs and their main metabolites were analyzed using high performance liquid chromatography assay. Bioequivalence was assessed for whole blood and plasma AUC and Cmax of chloroquine, proguanil, cycloguanil and 4-chlorophenylbiguanide. Bioequivalence in erythrocytes was also established except for Cmax of chloroquine. While the differences for Cmax of chloroquine in erythrocytes may be related to technical problems during the erythrocyte sampling procedure (contamination with leukocytes), bioequivalence can be concluded from the plasma concentration data. Therefore, the use of a single capsule instead of one chloroquine tablet and two proguanil tablets daily can be proposed in order to increase the prophylactic compliance without decreasing the prophylactic efficacy.
ISSN:0004-4172
DOI:10.1055/s-0031-1299906