Pharmacokinetics of melarsoprol in uninfected vervet monkeys

Burri, Christian; Onyango, J.D; Auma, Joanna E.; Burudi, E.M.E.; Brun, Reto

doi:10.1016/0001-706x(94)90120-1

Cited by 22 publications

(12 citation statements)

References 15 publications

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“…Generally, the activity of a drug may show considerable interanimal variation, which results in different concentrations at the site of action (kinetic differences) or different responses to a given drug concentration (dynamic differences) (19). Studies with melarsoprol, the drug used to treat late-stage sleeping sickness, similarly indicated that the peak levels attained in the CSF of monkeys were about 50 times less than peak levels in plasma and were insufficient in some animals to eliminate all trypanosomes from the CSF compartment (6).…”

Section: Discussionmentioning

confidence: 99%

Efficacy of the Novel Diamidine Compound 2,5-Bis(4-Amidinophenyl)- Furan-Bis- O -Methlylamidoxime (Pafuramidine, DB289) against Trypanosoma brucei rhodesiense Infection in Vervet Monkeys after Oral Administration

Mdachi

Thuita

Kagira

et al. 2009

Antimicrob Agents Chemother

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Section: Discussionmentioning

confidence: 99%

Efficacy of the Novel Diamidine Compound 2,5-Bis(4-Amidinophenyl)- Furan-Bis- O -Methlylamidoxime (Pafuramidine, DB289) against Trypanosoma brucei rhodesiense Infection in Vervet Monkeys after Oral Administration

Mdachi

Thuita

Kagira

et al. 2009

Antimicrob Agents Chemother

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“…Generally, 3-4 series of 3-4 injections of increasing doses are given, spaced with resting periods of 7-10 days. To optimize and standardize melarsoprol treatment, an abridged 10-day protocol has been elaborated on the basis of pharmacological investigations [7][8][9], animal experiments [10], and pilot testing of patients with HAT in the former Zaire [11]. The effectiveness of this regimen, in terms of safety and efficacy, in comparison with a standard treatment regimen was shown in a large-scale randomized clinical trial in Angola (the Improved Application of Melarsoprol [Impamel] I study) [12,13].…”

mentioning

confidence: 99%

Effectiveness of a 10‐Day Melarsoprol Schedule for the Treatment of Late‐Stage Human African Trypanosomiasis: Confirmation from a Multinational Study (ImpamelII)

Schmid

Richer²,

Bilenge

et al. 2005

J INFECT DIS

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The 10-day treatment schedule was well implemented in the field and was effective. It reduces treatment duration, drug amount, and hospitalization costs per patient, and it increases treatment-center capacity. The shorter protocol has been recommended by the International Scientific Council for Trypanosomiasis Research and Control for the treatment of late-stage HAT caused by Trypanosoma brucei gambiense.

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“…administration (Lee et al, 2006). Burri et al (1994) found both i.v. clearance and volume of distribution of the trypanocidal drug melarsoprol to be greater in African green monkeys than in humans, although data from other nonhuman primates are not available for this agent.…”

Section: Pharmacokinetics In African Green Monkeysmentioning

confidence: 99%

Exploration of the African Green Monkey as a Preclinical Pharmacokinetic Model: Intravenous Pharmacokinetic Parameters

Ward

Coon²,

Magiera³

et al. 2008

Drug Metab Dispos

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ABSTRACT:The value of cynomolgus and rhesus monkeys to predict human pharmacokinetic parameters has been well established in recent years. However, practical limitations on cost and accessibility can often be a deterrent to obtain data in these valuable species, and the characterization of the predictive power of other nonhuman primates would be useful. Therefore, the present investigation was designed to evaluate the pharmacokinetics of a test set of marketed compounds in the African green monkey, to compare the pharmacokinetics of these agents between nonhuman primate species, and to validate the ability of the African green monkey to predict human pharmacokinetics. Intravenous pharmacokinetics were evaluated for 11 test compounds in this study and compared with data from rats, dogs, cynomolgus/rhesus monkeys, and humans. The results from this investigation indicate that African green monkeys deliver reasonable prediction of human clearance and mean residence time and volume of distribution, although somewhat less accurately than cynomolgus and rhesus monkeys, particularly for volume of distribution, potentially because of body size or composition or experimental design differences. Furthermore, use of an optimized clearance prediction algorithm from the literature enhanced predictivity over a simple liver blood flowbased extrapolation methodology. The data from this study show that African green monkeys have the potential to be used as a surrogate for cynomolgus or rhesus monkeys in preclinical pharmacokinetic studies, particularly for the study of clearance processes, and should be considered as an alternate nonhuman primate test species.

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Pharmacokinetics of melarsoprol in uninfected vervet monkeys

Cited by 22 publications

References 15 publications

Efficacy of the Novel Diamidine Compound 2,5-Bis(4-Amidinophenyl)- Furan-Bis- O -Methlylamidoxime (Pafuramidine, DB289) against Trypanosoma brucei rhodesiense Infection in Vervet Monkeys after Oral Administration

Efficacy of the Novel Diamidine Compound 2,5-Bis(4-Amidinophenyl)- Furan-Bis- O -Methlylamidoxime (Pafuramidine, DB289) against Trypanosoma brucei rhodesiense Infection in Vervet Monkeys after Oral Administration

Effectiveness of a 10‐Day Melarsoprol Schedule for the Treatment of Late‐Stage Human African Trypanosomiasis: Confirmation from a Multinational Study (ImpamelII)

Exploration of the African Green Monkey as a Preclinical Pharmacokinetic Model: Intravenous Pharmacokinetic Parameters

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