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Measurement of the concentration of antimalarials in the blood of the general population helps estimating the overall drug pressure and is used in efficacy studies. The current sampling standard for drug measurement is plasma obtained by venous puncture. The use of a Dried Blood Spots (DBS) sampling strategy can make some aspects of field trials conditions easier, but concordance with usual venous sampling is not yet established.
The current work will allow validating the concentrations of lumefantrine measured in the DBS samples collected during the field trials and validate the use of DBS for future studies. In addition, bearing in mind the substantial deployment of artemether-lumefantrine combinations supplies throughout most malaria endemic countries, this study may improve our understanding of lumefantrine and artemether distribution in the blood compartments and generate knowledge for further developing analytical methods for drug measurement.
The overall purpose of this study is to validate the dried blood spots as a sampling method for the analysis of lumefantrine.
The primary objective is to assess the concordance between lumefantrine plasma and dried blood spots (DBS) concentrations.
The investigators also aim at describing lumefantrine's distribution in the different blood compartments: binding to plasma proteins, total in plasma, inside the red blood cells, total in whole blood.
(Details available on request)
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Artemether + lumefantrine | Other | One single adult dose of artemether + lumefantrine 80 + 480 mg |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Artemether + lumefantrine | Drug | A single adult dose of artemether-lumefantrine will be administered on a unique occasion together with food. Venous and capillary blood samples will be collected at 6 to 10 time points, as defined before drug administration with each volunteer. |
| Measure | Description | Time Frame |
|---|---|---|
| Concordance of concentrations of lumefantrine measured in dried capillary blood spot samples (DBS) and in plasma, at different time-points after the administration of a single oral adult dose of artemether-lumefantrine. | Within the first two weeks after drug intake |
| Measure | Description | Time Frame |
|---|---|---|
| Concordance of concentrations of desbutyl-lumefantrine measured in DBS and in plasma | Within the first two weeks after drug intake | |
| Concordance of lumefantrine and desbutyl-lumefantrine concentrations measured in dried venous blood spot samples and in plasma |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Thierry Buclin, Professor | Division of Clinical Pharmacology, University Hospital, Lausanne, Switzerland | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Division of Clinical Pharmacology | Lausanne | Canton of Vaud | 1011 | Switzerland |
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| ID | Term |
|---|---|
| D008288 | Malaria |
| ID | Term |
|---|---|
| D011528 | Protozoan Infections |
| D010272 | Parasitic Diseases |
| D007239 | Infections |
| D000096724 | Mosquito-Borne Diseases |
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| ID | Term |
|---|---|
| D000077611 | Artemether, Lumefantrine Drug Combination |
| ID | Term |
|---|---|
| D000077549 | Artemether |
| D037621 | Artemisinins |
| D017382 | Reactive Oxygen Species |
| D005609 | Free Radicals |
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|
| Within the first two weeks after drug intake |
| Concordance of concentration of lumefantrine and desbutyl-lumefantrine measured in whole venous blood and in plasma | Within the first two weeks after drug intake |
| Determination of a ratio of intra-erythrocyte and plasma concentrations of lumefantrine and desbutyl-lumefantrine over time (corrected for hematocrit) | Within the first two weeks after drug intake |
| Determination of a ratio of unbound plasma concentration and total plasma concentration of lumefantrine and desbutyl-lumefantrine over time | Within the first two weeks after drug intake |
| Determination of the limit of quantification of artemether and dihydroartemisinin in dried blood spots samples, using the standard method of a calibration curve | Within the first 24 hours after drug intake |
| Determination the relative precision of lumefantrine and desbutyl-lumefantrine concentrations in dried blood spots versus in plasma, using triplicate measurements and a hierarchical non-linear regression model | Within the first two weeks after drug intake |
| D000079426 |
| Vector Borne Diseases |
| D007287 |
| Inorganic Chemicals |
| D009930 | Organic Chemicals |
| D000078102 | Lumefantrine |
| D005449 | Fluorenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D012717 | Sesquiterpenes |
| D013729 | Terpenes |
| D011083 | Polycyclic Compounds |
| D004338 | Drug Combinations |
| D004364 | Pharmaceutical Preparations |