The concentration of chloroquine (CQ), dapsone (DDS) and pyrimethamine (PYR) in plasma and milk were measured following the coadministration of a single dose of chloroquine and Maloprim to lactating women. The milk to plasma area under the concentration‐time curve (AUC) ratio ranged from 1.96 to 4.26 for CQ, 0.22 to 0.45 for DDS and 0.46 to 0.66 for PYR. Assuming a daily milk ingestion of 1 l by the infant, the maximum percentage of the maternal dose for CQ, DDS and PYR in milk was 4.2%, 14.3% and 45.6%, respectively, over a 9 day period.
The DAM-LR (Distributed Access Management for Language Resources) project aims at virtually integrating various European language resource archives that allow users to navigate and operate in a single unified domain of language resources. This type of integration introduces Grid technology to the humanities disciplines and forms a federation of archives. It is the basis for establishing a research infrastructure for language resources which will finally enable eHumanities. Currently, the complete architecture is designed based on a few well-known components and some components have already been tested. Based on the technological insights gathered and due to discussions within the international DELAMAN (Digital Endangered Languages and Music Archives Network) network the ethical and organizational basis for such a federation is defined.
The pharmacokinetic parameters of chlorproguanil (Lapudrine®) and its active metabolite, chlorcycloguanil, were determined in 6 healthy male volunteers after a single oral dose of 4 Lapudrine tablets (80 mg). The mean maximum plasma chlorproguanil concentration was 36.7 ± (SD)7.9 ng/ml and was reached at 3.8+1.3 h. The chlorproguanil elimination half-life was 17.5 ± 6.7 h and its plasma clearance was 1.28 ± 0.12 1/h/kg. The mean whole blood to plasma ratio was 3.1 at 4 h after dosing. Chlorcycloguanil could not be quantified in plasma and whole blood at the detection limit of 10 ng/ml using a high-performance liquid chromatographic method. An excretion rate-time plot from urine data shows a rapid (t½ = 20 h) and a slow phase (t½ = 51 h) in the elimination of chlorcycloguanil. Our findings suggest that the current prophylactic regimen of chlorproguanil hydrochloride (20 mg weekly) may not be optimal in preventing infections with chloroquine-resistant falciparum malaria.
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