Pharmacokinetics and Pharmacodynamics of Intravenous Artesunate for Severe Malaria Treatment

Study Overview
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Brief Summary
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Intravenous artesunate is highly effective with rapid schizonticidal action and improved clinical outcome

Detailed Description
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The current first line treatment for severe malaria in Uganda is intravenous quinine with artemisinin derivatives as an alternative. Intravenous artesunate, a water soluble artemisinin derivative is more effective than quinine with faster schizonticidal action and improved clinical outcome. It is generally well tolerated and safe. This study aims is to assess the pharmacokinetics, pharmacodynamics and safety of IV artesunate in treatment of severe malaria in adults admitted to Mulago National Referral and Teaching hospital, Uganda.

Official Title
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Pharmacokinetics and Pharmacodynamics of Intravenous Artesunate in Treatment of Severe Malaria in Ugandan Patients

Conditions
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Severe Malaria

Intervention / Treatment
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* Drug: intravenous artesunate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged 18 years and above With severe malaria according to the following ciriteria: A positive blood smear for malaria with P. falciparum mono-infection with parasitemia > 500 parasites/ul of blood Who according to the attending physician require parenteral treatment and admission for malaria Willing to participate in the study Who are or whose first degree parents/caretakers are able to provide written informed consent Exclusion Criteria: Patients with history of prior antimalarial use within the last 72 hours Pregnant women Patients with contraindications to taking the study drugs Patients taking known inhibitors or inducers of cytochrome P450 -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 20 adults with severe malaria<br>20 adult patients admitted with severe malaria | Drug: intravenous artesunate<br>* Intravenous artesunate in a dose of 2.4 mg/kg at start of treatment, 2.4 mg/kg 12 hours later and 2.4 mg/kg/day until the patient is able to tolerate oral therapy. The minimum duration of IV treatment will be 24 hours.<br>* Other names: Artesun®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameters; total area under the plasma concentration vs. time curve (AUC) of artesunate and DHA, maximum plasma concentration (Cmax), time to attain maximum concentration, elimination half life | Pharmacokinetic parameters for artesunate and dihydroartemisinin | 6 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to 50% parasite clearance (PCT50) | Time to 50% parasite clearance (PCT50) parasite clearance rates and clinical recovery | 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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severe, malaria, artesunate, intravenous