{"id":{"repo_id":"rgu","oai_identifier":"oai:rgu-repository.worktribe.com:2807287"},"canonical_url":"https://search.dev.ndltd.org/etd/rgu/oai:rgu-repository.worktribe.com:2807287","repository":{"repo_id":"rgu","name":"Robert Gordon University","base_url":"https://rgu-repository.worktribe.com/oaiprovider"},"display":{"title":"The efficacy and safety of artesunate suppositories in combination with other antimalarials in the treatment of severe malaria in Sudan.","abstract":"There is a limited documentation on the efficacy of artesunate in Africa with no experience in Sudan. Severe malaria in Sudan is common in its rural areas where lack of facilities for the safe and effective parenteral use of quinine causes long delays before the patient can reach a suitable centre for treatment. An early treatment with artesunate suppositones as a simple method by unskilled staff is an alternative approach that is needed to save lives. Due to the inadequate documentation of the pharmacokinetics and pharmacodynamics of artesunate in Africa and particularly in Sudan, this study is designed to provide a definitive contribution to knowledge about artesunate disposition, efficacy and safety in Sudanese population. The present results will be pooled with those from other different areas to help in the improvement of the actual assessment of the efficacy and safety of artesunate suppositories, and the survival benefit in the treatment of severe malaria. The results of this study revealed the efficacy of a novel dosage regimen of artesunate suppositories, and the comparative efficacy and safety of three combined antimalarials in preventing recrudescence. The modified HPLC-UV method used in the present study showed appropriate validation and provided accurate characterisation and quantification of artesunate, alpha and beta dihydroartemisinin and artemisinin in pooled plasma. Difficulties encountered in the analysis of the Sudanese subject plasma samples were overcome by developing alternative chromatographic methodology. An ion-pairing HPLC method was developed which proved its capability in the determination of artesunate in the presence of metabolites and represents an alternative approach to the chromatography of this compound for pharmacokinetic studies. Both plasma assay methods used in this study met the criteria for use in pharmacokinetic studies. A pharmacokinetic study of artesunate in 14 healthy Sudanese volunteers has been carried out following oral and rectal administration of 200mg sodium artesunate. Since artesunate was rapidly eliminated from the plasma, the pharmacokinetic evaluation was determined from the metabolite dihydroartemisinin rather than artesunate. The major pharmacokinetic parameters of dihydroartemisinm tmax (h), Cmax (ng/ml), Ka (h-1), Ke (h-1), t1/jKe (h) and AUCo-infinity (ng.h/ml) are reported for both oral and rectal dosing. For oral dosing these were determined as 1.43±0.92, 593.5±327.6, 5.98±5.42, 0.66±0.33, 1.39±0.89, 2124±1073.6 and for rectal administration as 1.97±0.72, 207.7±149.7, 1.57±1.15, 0.55±0.28, 1.65±1.11, 1087.3±959.4. The relative bioavailability between rectal and oral routes was calculated as 54.2±41.4. On the basis of the pharmacokinetic results obtained, a novel dosage regimen for rectal artesunate dosing in patients with severe falciparum malaria is proposed. The results of an extended clinical trial in Sudan showed that the suggested dose of rectal artesunate (200mg/8h) for 3 days halted the severe disease progression and prevented fatal outcomes. Treatment of severe malaria with this suggested dose resulted in rapid clinical response, shorter parasite clearance time (31.5±10.1h) and fever subsidence time (31.4±ll.lh) than had been observed in previous studies. The present results indicate that the sequential treatment of severe malaria with artesunate rectocaps followed by doxycycline or pyrimethamine/sulphadoxine or mefloquine resulted in clinical cure rates of 100%, 100% and 96.7% respectively. The combination with either doxycycline or pynmethamine/sulphadoxine is equally effective to that followed by mefloquine in preventing recrudescence. The three combination regimens provided a radical cure rate 100% that is significantly higher than previously reported either in treatment of uncomplicated or severe malaria. The three combination regimens are highly effective, and could be life saving in patients with severe malaria, particularly in rural areas. Significant adverse effects or signs of toxicity have not been observed in this study and the benefit of a potentially life saving treatment outweighs the risk of the observed side effects.","abstract_html":"There is a limited documentation on the efficacy of artesunate in Africa with no experience in Sudan. Severe malaria in Sudan is common in its rural areas where lack of facilities for the safe and effective parenteral use of quinine causes long delays before the patient can reach a suitable centre for treatment. An early treatment with artesunate suppositones as a simple method by unskilled staff is an alternative approach that is needed to save lives. Due to the inadequate documentation of the pharmacokinetics and pharmacodynamics of artesunate in Africa and particularly in Sudan, this study is designed to provide a definitive contribution to knowledge about artesunate disposition, efficacy and safety in Sudanese population. The present results will be pooled with those from other different areas to help in the improvement of the actual assessment of the efficacy and safety of artesunate suppositories, and the survival benefit in the treatment of severe malaria. The results of this study revealed the efficacy of a novel dosage regimen of artesunate suppositories, and the comparative efficacy and safety of three combined antimalarials in preventing recrudescence. The modified HPLC-UV method used in the present study showed appropriate validation and provided accurate characterisation and quantification of artesunate, alpha and beta dihydroartemisinin and artemisinin in pooled plasma. Difficulties encountered in the analysis of the Sudanese subject plasma samples were overcome by developing alternative chromatographic methodology. An ion-pairing HPLC method was developed which proved its capability in the determination of artesunate in the presence of metabolites and represents an alternative approach to the chromatography of this compound for pharmacokinetic studies. Both plasma assay methods used in this study met the criteria for use in pharmacokinetic studies. A pharmacokinetic study of artesunate in 14 healthy Sudanese volunteers has been carried out following oral and rectal administration of 200mg sodium artesunate. Since artesunate was rapidly eliminated from the plasma, the pharmacokinetic evaluation was determined from the metabolite dihydroartemisinin rather than artesunate. The major pharmacokinetic parameters of dihydroartemisinm tmax (h), Cmax (ng/ml), Ka (h-1), Ke (h-1), t1/jKe (h) and AUCo-infinity (ng.h/ml) are reported for both oral and rectal dosing. For oral dosing these were determined as 1.43±0.92, 593.5±327.6, 5.98±5.42, 0.66±0.33, 1.39±0.89, 2124±1073.6 and for rectal administration as 1.97±0.72, 207.7±149.7, 1.57±1.15, 0.55±0.28, 1.65±1.11, 1087.3±959.4. The relative bioavailability between rectal and oral routes was calculated as 54.2±41.4. On the basis of the pharmacokinetic results obtained, a novel dosage regimen for rectal artesunate dosing in patients with severe falciparum malaria is proposed. The results of an extended clinical trial in Sudan showed that the suggested dose of rectal artesunate (200mg/8h) for 3 days halted the severe disease progression and prevented fatal outcomes. Treatment of severe malaria with this suggested dose resulted in rapid clinical response, shorter parasite clearance time (31.5±10.1h) and fever subsidence time (31.4±ll.lh) than had been observed in previous studies. The present results indicate that the sequential treatment of severe malaria with artesunate rectocaps followed by doxycycline or pyrimethamine/sulphadoxine or mefloquine resulted in clinical cure rates of 100%, 100% and 96.7% respectively. The combination with either doxycycline or pynmethamine/sulphadoxine is equally effective to that followed by mefloquine in preventing recrudescence. The three combination regimens provided a radical cure rate 100% that is significantly higher than previously reported either in treatment of uncomplicated or severe malaria. The three combination regimens are highly effective, and could be life saving in patients with severe malaria, particularly in rural areas. Significant adverse effects or signs of toxicity have not been observed in this study and the benefit of a potentially life saving treatment outweighs the risk of the observed side effects.","abstract_has_math":false,"creators":["Awad, Abdelmoneim Ismail"],"institution":"Robert Gordon University","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["R.B. Taylor, I.B. Eltayeb, A. Alkadro, O.Z. Barka and D.G. Durham"],"committee_chairs":[],"committee_members":[],"year":2001,"date_issued":"2001","date_published":"2001","updated_at":"2026-07-24T04:10:09Z","subjects":["Artesunate","Severe malaria","Sudan","Pharmacokinetics","Efficacy","Rectal administration","Combination regimens","Clinical trials"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["oai:rgu-repository.worktribe.com:2807287","https://doi.org/10.48526/rgu-wt-2807287"],"render_values":[{"text":"oai:rgu-repository.worktribe.com:2807287","href":null,"code":true},{"text":"https://doi.org/10.48526/rgu-wt-2807287","href":"https://doi.org/10.48526/rgu-wt-2807287","code":true}]}]},"links":{"outbound_url":"https://rgu-repository.worktribe.com/2807287/1/AWAD%202001%20The%20efficacy%20and%20safety%20of%20artesunate","outbound_label":"Repository record","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["R.B. 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Severe malaria in Sudan is common in its rural areas where lack of facilities for the safe and effective parenteral use of quinine causes long delays before the patient can reach a suitable centre for treatment. An early treatment with artesunate suppositones as a simple method by unskilled staff is an alternative approach that is needed to save lives. Due to the inadequate documentation of the pharmacokinetics and pharmacodynamics of artesunate in Africa and particularly in Sudan, this study is designed to provide a definitive contribution to knowledge about artesunate disposition, efficacy and safety in Sudanese population. The present results will be pooled with those from other different areas to help in the improvement of the actual assessment of the efficacy and safety of artesunate suppositories, and the survival benefit in the treatment of severe malaria. The results of this study revealed the efficacy of a novel dosage regimen of artesunate suppositories, and the comparative efficacy and safety of three combined antimalarials in preventing recrudescence. The modified HPLC-UV method used in the present study showed appropriate validation and provided accurate characterisation and quantification of artesunate, alpha and beta dihydroartemisinin and artemisinin in pooled plasma. Difficulties encountered in the analysis of the Sudanese subject plasma samples were overcome by developing alternative chromatographic methodology. An ion-pairing HPLC method was developed which proved its capability in the determination of artesunate in the presence of metabolites and represents an alternative approach to the chromatography of this compound for pharmacokinetic studies. Both plasma assay methods used in this study met the criteria for use in pharmacokinetic studies. A pharmacokinetic study of artesunate in 14 healthy Sudanese volunteers has been carried out following oral and rectal administration of 200mg sodium artesunate. Since artesunate was rapidly eliminated from the plasma, the pharmacokinetic evaluation was determined from the metabolite dihydroartemisinin rather than artesunate. The major pharmacokinetic parameters of dihydroartemisinm tmax (h), Cmax (ng/ml), Ka (h-1), Ke (h-1), t1/jKe (h) and AUCo-infinity (ng.h/ml) are reported for both oral and rectal dosing. For oral dosing these were determined as 1.43±0.92, 593.5±327.6, 5.98±5.42, 0.66±0.33, 1.39±0.89, 2124±1073.6 and for rectal administration as 1.97±0.72, 207.7±149.7, 1.57±1.15, 0.55±0.28, 1.65±1.11, 1087.3±959.4. The relative bioavailability between rectal and oral routes was calculated as 54.2±41.4. On the basis of the pharmacokinetic results obtained, a novel dosage regimen for rectal artesunate dosing in patients with severe falciparum malaria is proposed. The results of an extended clinical trial in Sudan showed that the suggested dose of rectal artesunate (200mg/8h) for 3 days halted the severe disease progression and prevented fatal outcomes. Treatment of severe malaria with this suggested dose resulted in rapid clinical response, shorter parasite clearance time (31.5±10.1h) and fever subsidence time (31.4±ll.lh) than had been observed in previous studies. The present results indicate that the sequential treatment of severe malaria with artesunate rectocaps followed by doxycycline or pyrimethamine/sulphadoxine or mefloquine resulted in clinical cure rates of 100%, 100% and 96.7% respectively. The combination with either doxycycline or pynmethamine/sulphadoxine is equally effective to that followed by mefloquine in preventing recrudescence. The three combination regimens provided a radical cure rate 100% that is significantly higher than previously reported either in treatment of uncomplicated or severe malaria. The three combination regimens are highly effective, and could be life saving in patients with severe malaria, particularly in rural areas. Significant adverse effects or signs of toxicity have not been observed in this study and the benefit of a potentially life saving treatment outweighs the risk of the observed side effects."]},{"key":"dc:title","label":"Title","values":["The efficacy and safety of artesunate suppositories in combination with other antimalarials in the treatment of severe malaria in Sudan."]}]}],"canonical_facts":{"dc:contributor.advisor":["R.B. Taylor, I.B. Eltayeb, A. Alkadro, O.Z. Barka and D.G. Durham"],"dc:contributor.sponsor":["No Funder Acknowledged (Outputs)"],"dc:creator":["Awad, Abdelmoneim Ismail"],"dc:date":["2001-08-31"],"dc:date.issued":["2001"],"dc:description.abstract":["There is a limited documentation on the efficacy of artesunate in Africa with no experience in Sudan. Severe malaria in Sudan is common in its rural areas where lack of facilities for the safe and effective parenteral use of quinine causes long delays before the patient can reach a suitable centre for treatment. An early treatment with artesunate suppositones as a simple method by unskilled staff is an alternative approach that is needed to save lives. Due to the inadequate documentation of the pharmacokinetics and pharmacodynamics of artesunate in Africa and particularly in Sudan, this study is designed to provide a definitive contribution to knowledge about artesunate disposition, efficacy and safety in Sudanese population. The present results will be pooled with those from other different areas to help in the improvement of the actual assessment of the efficacy and safety of artesunate suppositories, and the survival benefit in the treatment of severe malaria. The results of this study revealed the efficacy of a novel dosage regimen of artesunate suppositories, and the comparative efficacy and safety of three combined antimalarials in preventing recrudescence. The modified HPLC-UV method used in the present study showed appropriate validation and provided accurate characterisation and quantification of artesunate, alpha and beta dihydroartemisinin and artemisinin in pooled plasma. Difficulties encountered in the analysis of the Sudanese subject plasma samples were overcome by developing alternative chromatographic methodology. An ion-pairing HPLC method was developed which proved its capability in the determination of artesunate in the presence of metabolites and represents an alternative approach to the chromatography of this compound for pharmacokinetic studies. Both plasma assay methods used in this study met the criteria for use in pharmacokinetic studies. A pharmacokinetic study of artesunate in 14 healthy Sudanese volunteers has been carried out following oral and rectal administration of 200mg sodium artesunate. Since artesunate was rapidly eliminated from the plasma, the pharmacokinetic evaluation was determined from the metabolite dihydroartemisinin rather than artesunate. The major pharmacokinetic parameters of dihydroartemisinm tmax (h), Cmax (ng/ml), Ka (h-1), Ke (h-1), t1/jKe (h) and AUCo-infinity (ng.h/ml) are reported for both oral and rectal dosing. For oral dosing these were determined as 1.43±0.92, 593.5±327.6, 5.98±5.42, 0.66±0.33, 1.39±0.89, 2124±1073.6 and for rectal administration as 1.97±0.72, 207.7±149.7, 1.57±1.15, 0.55±0.28, 1.65±1.11, 1087.3±959.4. The relative bioavailability between rectal and oral routes was calculated as 54.2±41.4. On the basis of the pharmacokinetic results obtained, a novel dosage regimen for rectal artesunate dosing in patients with severe falciparum malaria is proposed. The results of an extended clinical trial in Sudan showed that the suggested dose of rectal artesunate (200mg/8h) for 3 days halted the severe disease progression and prevented fatal outcomes. Treatment of severe malaria with this suggested dose resulted in rapid clinical response, shorter parasite clearance time (31.5±10.1h) and fever subsidence time (31.4±ll.lh) than had been observed in previous studies. The present results indicate that the sequential treatment of severe malaria with artesunate rectocaps followed by doxycycline or pyrimethamine/sulphadoxine or mefloquine resulted in clinical cure rates of 100%, 100% and 96.7% respectively. The combination with either doxycycline or pynmethamine/sulphadoxine is equally effective to that followed by mefloquine in preventing recrudescence. The three combination regimens provided a radical cure rate 100% that is significantly higher than previously reported either in treatment of uncomplicated or severe malaria. The three combination regimens are highly effective, and could be life saving in patients with severe malaria, particularly in rural areas. Significant adverse effects or signs of toxicity have not been observed in this study and the benefit of a potentially life saving treatment outweighs the risk of the observed side effects."],"dc:identifier":["oai:rgu-repository.worktribe.com:2807287","https://doi.org/10.48526/rgu-wt-2807287"],"dc:identifier.uri":["https://rgu-repository.worktribe.com/2807287/1/AWAD%202001%20The%20efficacy%20and%20safety%20of%20artesunate"],"dc:language":["en"],"dc:publisher.institution":["Robert Gordon University"],"dc:relation.isreferencedby":["https://rgu-repository.worktribe.com/output/2807287"],"dc:subject":["Artesunate","Severe malaria","Sudan","Pharmacokinetics","Efficacy","Rectal administration","Combination regimens","Clinical trials"],"dc:title":["The efficacy and safety of artesunate suppositories in combination with other antimalarials in the treatment of severe malaria in Sudan."],"dc:type":["Thesis"]},"updated_at":"2026-07-24T04:10:09Z"}