Treatment of Rhodesian sleeping sickness in Kenya

Wellde, B. T.; Chumo, D. A.; Reardon, Michael J.; Abinya, A; Wanyama, L.; Dola, S.; Mbwabi, D.; Smith, David H.; Siongok, T. A.

doi:10.1080/00034983.1989.11812413

Cited by 18 publications

(6 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Relapses after mclarsoprol treatment have been reported in 1-10% of cases [3,4]. Melarsoprol-resistant T.b.…”

Section: Discussionmentioning

confidence: 99%

“…Approximately 50 million people arc living at risk from the di sease [1], Melarsoprol, a melaminyl-phenyl-arsenoxide, is still the most common drug used for treatment of the second stage of the disease when trypanosomes invade the central ner vous system [2]. It shows an excellent antitrypanocidal activity, but relapses have been re ported in 1-10% of cases [3,4] and it can have severe side effects. Vertigo, vomiting and diar rhea are common, and 2-10% of the treated patients suffer a reactive encephalopathy [5] which is always life-threatening.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Pharmacokinetic Properties of the Trypanocidal Drug Melarsoprol

Burri

Baltz²,

Giroud³

et al. 1993

Chemotherapy

View full text Add to dashboard Cite

With a biological assay and atomic absorption spectrometry we determined the level of melarsoprol in the serum and cerebrospinal fluid of 19 patients treated with melarsoprol in Daloa, Ivory Coast. Most serum levels were between 2 and 4 μg/ml 24 h after administration, and were still ≥0.1 μg/ml after 120 h. Levels in the cerebrospinal fluid were between 0 and 0.1 μg/ml. Elimination was biphasic, with a pronounced β₁ phase. Mean terminal elimination half-life of melarsoprol was about 35 h, volume of distribution was about 1001 and total clearance was about 50 ml/min. The results of these first pharmacokinetic studies on melarsoprol were used to simulate possible alternative therapy schemes which might avoid some of the problems that arise with melarsoprol use.

show abstract

“…Relapses after mclarsoprol treatment have been reported in 1-10% of cases [3,4]. Melarsoprol-resistant T.b.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic Properties of the Trypanocidal Drug Melarsoprol

Burri

Baltz²,

Giroud³

et al. 1993

Chemotherapy

View full text Add to dashboard Cite

show abstract

“…It is important in East African disease to verifY the lack of central nervous system (CNS) involvement by examining the CSF. Patients who, on merely clinical grounds, are thought not to have CNS involvement and are then treated with suramin have a high (49%) rate of neurological relapse (Wellde et al 1989). Recently, the ornithine decarboxylase inhibitor difluoromethylornithine has been approved for the treatment of West African disease including disease with CNS involvement.…”

Section: African Trypanosomiasismentioning

confidence: 98%

“…The suggested course of treatment at that time was 4 intravenous injections of 3.6 mg/kg each in the first week, I week with no treatment and then a repeat series of 4 injections for a total dose of ",,29 mg/kg. Wellde et al (1989) note that 'typical' treatment schedules in Kenya are 3 doses per week for each of 4 weeks, with most injections containing a higher dose than the previous injection, for a total dosage of 37.5 mg/kg. As is frequently seen with antiparasitic drugs for which the resources necessary for formal investigation are limited, these dosage regimens have been developed through clinical trial and error.…”

Section: Agents Active Against Trypanosomiasismentioning

confidence: 99%

Pharmacokinetic Justification of Antiprotozoal Therapy

Berman

Fleckenstein

1991

Clinical Pharmacokinetics

View full text Add to dashboard Cite

Infections with parasitic protozoa have always been problems for the developing world and are becoming of greater importance to the developed world in this age of easy international travel. The major human protozoal diseases are summarised with an emphasis on their presentation in normal hosts and in immunocompromised individuals and current US drug treatment recommendations are discussed. Present antiprotozoal regimens are based either on a pharmacokinetic rationale or on clinical trial and error. Regimens based on trial and error include amphotericin B against leishmaniasis and arsenic against African trypanosomiasis. Regimens which are to some extent driven by pharmacokinetic or biochemical considerations include paromomycin and metronidazole against amoebiasis, sodium stibogluconate against leishmaniasis, halofantrine and mefloquine against malaria, dihydrofolate reductase (DHFR) inhibitors against Pneumocystis carinii and toxoplasmosis and aerosolised pentamidine against P. carinii pneumonia. The majority of pharmacokinetic studies have been performed only on agents which have some therapeutic activity against other diseases of the developed world. Despite the trend toward rational treatment regimens, no studies have been performed that permit optimisation of antiprotozoal treatment regimens on the basis of clinical conditions such as renal failure.

show abstract

“…Treatment with suramin may have a relapse rate of up to 49%, based on clinical signs but no lumbar puncture in patients infected with T. b. rhodesiense [34]. However, only 6.9% of patients with CSF white blood cell counts less than 6 cells/mm 3 had relapses.…”

Section: Suramin (Bayer 205 Germanin ò )mentioning

confidence: 99%

Treatment perspectives for human African trypanosomiasis

Bouteille

Oukem

Bisser

et al. 2003

Fundamemntal Clinical Pharma

135

112

View full text Add to dashboard Cite

Human African trypanosomiasis (HAT), or sleeping sickness, is currently on the rise. HAT develops in two stages, the first involving the hemolymphatic system, and the second, the neurological system. Left untreated, HAT is invariably fatal. There have been no therapeutic advances in more than 40 years. Stage 1 can be treated with pentamidine and suramin, but stage 2 can only be treated with melarsoprol, a toxic arsenic derivative that has a 2-12% incidence of fatal side-effects (encephalopathy). Eflornithine has never achieved widespread use because it is difficult to administer under field conditions. Nifurtimox has been used successfully in the treatment of American trypanosomiasis, or Chagas disease, but only in small studies or as a compassionate use treatment. There is little research and development for new drugs in this area: only one prodrug is in the clinical development phase, a pentamidine analog that offers hope for the replacement of injectable pentamidine with an orally administered drug. Current efforts appear to be focused on reevaluating older drugs. A course of treatment with melarsoprol for 10 days at 2.2 mg/kg/day is now in the multicenter evaluation phase. Orally administered eflornithine is also slated for reevaluation. In addition, studies of drug combinations are recommended to determine possible combined or synergistic effects and find ways to reduce toxicity.

show abstract

Treatment of Rhodesian sleeping sickness in Kenya

Cited by 18 publications

References 0 publications

Pharmacokinetic Properties of the Trypanocidal Drug Melarsoprol

Pharmacokinetic Properties of the Trypanocidal Drug Melarsoprol

Pharmacokinetic Justification of Antiprotozoal Therapy

Treatment perspectives for human African trypanosomiasis

Contact Info

Product

Resources

About