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J K Baird - One of the best experts on this subject based on the ideXlab platform.
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IN VIVO TEST AND POLYMERASE CHAIN REACTION GENOTYPING
2015Co-Authors: Go E. Mez-saladĺn, Kevin C Kain, Le Dinh Cong, J K BairdAbstract:Abstract. Chloroquine-resistant Plasmodium vivax malaria is emerging in Oceania, Asia, and Latin America. We assessed the drug sensitivity of P. vivax to chloroquine or Halofantrine in two villages in southern, central Vietnam. This area has chloroquine-resistant Plasmodium falciparum but no documented chloroquine-resistant P. vivax. Stan-dard dose chloroquine (25 mg/kg, over 48 hours) or Halofantrine (8 mg/kg, 3 doses) was administered to 29 and 25 patients, respectively. End points were parasite sensitivity or resistance determined at 28 days. Of the evaluable patients, 23/23 100 % (95 % confidence interval [CI] 85.1–100) chloroquine and 21/24 (87.5%) (95 % CI 67.6–97.3) Halofantrine-treated patients were sensitive. Three Halofantrine recipients had initial clearance but subsequent recur-rence of their parasitemias. Genotyping of the recurrent and Day 0 parasitemias differed, suggesting either new infections or relapses of liver hypnozoites from antecedent infections. Among these Vietnamese patients, P. vivax was sensitive to chloroquine and Halofantrine. Genotyping was useful for differentiating the recurrent vivax parasit-emias
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Short report: in vivo sensitivity of Plasmodium falciparum to Halofantrine in southern central Vietnam.
The American Journal of Tropical Medicine and Hygiene, 2003Co-Authors: Doan Hanh Nhan, Walter R J Taylor, David J Fryauff, Nguyen Dieu Thuong, Tran Thi Uyen, Ika Susanti, Eduardo Gómez-saladín, Le Dinh Cong, J K BairdAbstract:Drug-resistant Plasmodium falciparum is present in Vietnam. We assessed the in vivo sensitivity of P. falciparum to Halofantrine in two villages in the southern part of central Vietnam. Halofantrine (8 mg/kg × 3 doses) was administered to 37 patients with either P. falciparum (n 32) or mixed P. falciparum/P. vivax malaria (n 5). End points were parasite sensitivity or resistance (RI/RII/RIII) determined by parasite clearance, persistence, or recurrence during 28 days of follow-up. By day 28, 31 (93.9%) of 33 (95% confidence interval 79.8�99.2%) patients were sensitive. Two patients had recurrent P. falciparum parasitemia on days 14 and 21. Halofantrine effectively treated uncomplicated P. falciparum malaria in these Vietnamese patients.
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assessing drug sensitivity of plasmodium vivax to Halofantrine or choroquine in southern central vietnam using an extended 28 day in vivo test and polymerase chain reaction genotyping
American Journal of Tropical Medicine and Hygiene, 2000Co-Authors: Walter R J Taylor, H N Doan, D T Nguyen, T U Tran, David J Fryauff, Eduardo Gomezsaladin, Kevin C Kain, J K BairdAbstract:Chloroquine-resistant Plasmodium vivax malaria is emerging in Oceania, Asia, and Latin America. We assessed the drug sensitivity of P. vivax to chloroquine or Halofantrine in two villages in southern, central Vietnam. This area has chloroquine-resistant Plasmodium falciparum but no documented chloroquine-resistant P. vivax. Standard dose chloroquine (25 mg/kg, over 48 hours) or Halofantrine (8 mg/kg, 3 doses) was administered to 29 and 25 patients, respectively. End points were parasite sensitivity or resistance determined at 28 days. Of the evaluable patients, 23/23 100% (95% confidence interval [CI] 85.1-100) chloroquine and 21/24 (87.5%) (95% CI 67.6-97.3) Halofantrine-treated patients were sensitive. Three Halofantrine recipients had initial clearance but subsequent recurrence of their parasitemias. Genotyping of the recurrent and Day 0 parasitemias differed, suggesting either new infections or relapses of liver hypnozoites from antecedent infections. Among these Vietnamese patients, P. vivax was sensitive to chloroquine and Halofantrine. Genotyping was useful for differentiating the recurrent vivax parasitemias.
Dion R. Brocks - One of the best experts on this subject based on the ideXlab platform.
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Effect of experimental hyperlipidaemia on the electrocardiographic effects of repeated doses of Halofantrine in rats
British Journal of Pharmacology, 2010Co-Authors: Jigar P. Patel, Dion R. BrocksAbstract:BACKGROUND AND PURPOSE Halofantrine can cause a prolongation of the cardiac QT interval, leading to serious ventricular arrhythmias. Hyperlipidaemia elevates plasma concentration of Halofantrine and may influence its tissue uptake. The present study examined the effect of experimental hyperlipidaemia on QT interval prolongation induced by Halofantrine in rats. EXPERIMENTAL APPROACH Normolipidaemic and hyperlipidaemic rats (induced with poloxamer 407) were given 4 doses of Halofantrine (i.v., 4–40 mg·kg−1·d−1) or vehicle every 12 h. Under brief anaesthesia, ECGs were recorded before administration of the vehicle or drug and 12 h after the first and last doses. Blood samples were taken at the same time after the first and last dose of Halofantrine. Hearts were also collected 12 h after the last dose. Plasma and heart samples were assayed for drug and desbutylHalofantrine using a stereospecific method. KEY RESULTS In the vehicle group, hyperlipidaemia by itself did not affect the ECG. Compared to baseline, QT intervals were significantly higher in both normolipidaemic and hyperlipidaemic rats after Halofantrine. In hyperlipidaemic rats, plasma but not heart concentrations of the Halofantrine enantiomers were significantly higher compared to those in normolipidaemic rats. Despite the lack of difference in the concentrations of Halofantrine in heart, QT intervals were significantly higher in hyperlipidaemic compared to those in normolipidaemic rats. CONCLUSIONS AND IMPLICATIONS The unbound fraction of Halofantrine appeared to be the controlling factor for drug uptake by the heart. Our data suggested a greater vulnerability to Halofantrine-induced QT interval prolongation in the hyperlipidaemic state.
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Effect of bile and lipids on the stereoselective metabolism of Halofantrine by rat everted-intestinal sacs.
Chirality, 2010Co-Authors: Jigar P. Patel, Hesham M. Korashy, Ayman O.s. El-kadi, Dion R. BrocksAbstract:The everted rat intestinal-sac model was utilized to assess the effect of post-prandial conditions on the stereoselective intestinal metabolism of Halofantrine to its active metabolite desbutylHalofantrine. Everted intestinal sacs were incubated with (+/-)-Halofantrine HCl in the presence of simulated bile solution (containing lecithin, lipase and cholesterol) and lipids to mimic post-prandial conditions in the small intestine. The Halofantrine enantiomer concentrations in intestinal sacs were relatively constant in the presence of bile, but decreased significantly on addition of lipids to the incubation media. Formation of desbutylHalofantrine enantiomers was inversely proportional to bile concentration whereas addition of lipids in the presence of bile caused a significant decrease in desbutylHalofantrine:Halofantrine ratio of (-) enantiomers. Pre-treatment of rats with peanut oil had no significant effect on desbutylHalofantrine formation in the incubated sacs or microsomal preparations, nor did it affect the expression of intestinal cytochrome P450. Addition of extra cholesterol to the bile incubations caused a significant increase in tissue Halofantrine and desbutylHalofantrine concentrations, which as for lower cholesterol, were diminished on addition of other lipids. The results were consistent with previous in vivo evaluations showing that the desbutylHalofantrine to Halofantrine ratio was decreased by the ingestion of a high fat meal.
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the influence of lipids on stereoselective pharmacokinetics of Halofantrine important implications in food effect studies involving drugs that bind to lipoproteins
Journal of Pharmaceutical Sciences, 2002Co-Authors: Dion R. Brocks, Kishor M. WasanAbstract:The objective of this study was to determine the effect of lipids on the pharmacokinetics of Halofantrine enantiomers. Rats were given (+/-)-Halofantrine HCl 2 mg/kg i.v., or 7 mg/kg orally. Some rats were rendered hyperlipidemic by intraperitoneal administration of poloxamer 407 1 g/kg, followed by (+/-)-Halofantrine HCl intravenously. In other normolipidemic rats, (+/-)-Halofantrine was administered under fasted conditions, or after peanut oil given orally. Halofantrine enantiomer plasma concentrations were considerably (>10-fold) increased in hyperlipidemia. Decreases were noted in the clearance, volume of distribution and the unbound fraction in plasma of the hyperlipidemic rats. Peanut oil caused a significant 28% reduction in clearance of the (-), but not the (+) enantiomer (mean clearance reduced 11%) of Halofantrine. After oral Halofantrine, peanut oil resulted in a two- to threefold increase in the plasma area under the curves of Halofantrine enantiomers. Halofantrine enantiomer pharmacokinetics are highly dependent upon plasma lipid concentrations. Oral lipids may result in a stereoselective interaction at the level of clearance. Because lipids may affect clearance of drugs that bind to lipoproteins, in determining bioavailability of such drugs in food-effect studies, reference intravenous groups should be included to separate true increase in bioavailability from the effects of decreased clearance.
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the influence of lipids on stereoselective pharmacokinetics of Halofantrine important implications in food effect studies involving drugs that bind to lipoproteins
Journal of Pharmaceutical Sciences, 2002Co-Authors: Dion R. Brocks, Kishor M. WasanAbstract:Abstract The objective of this study was to determine the effect of lipids on the pharmacokinetics of Halofantrine enantiomers. Rats were given (±)‐Halofantrine HCl 2 mg/kg i.v., or 7 mg/kg orally. Some rats were rendered hyperlipidemic by intraperitoneal administration of poloxamer 407 1 g/kg, followed by (±)‐Halofantrine HCl intravenously. In other normolipidemic rats, (±)‐Halofantrine was administered under fasted conditions, or after peanut oil given orally. Halofantrine enantiomer plasma concentrations were considerably (>10‐fold) increased in hyperlipidemia. Decreases were noted in the clearance, volume of distribution and the unbound fraction in plasma of the hyperlipidemic rats. Peanut oil caused a significant 28% reduction in clearance of the (−), but not the (+) enantiomer (mean clearance reduced 11%) of Halofantrine. After oral Halofantrine, peanut oil resulted in a two‐ to threefold increase in the plasma area under the curves of Halofantrine enantiomers. Halofantrine enantiomer pharmacokinetics are highly dependent upon plasma lipid concentrations. Oral lipids may result in a stereoselective interaction at the level of clearance. Because lipids may affect clearance of drugs that bind to lipoproteins, in determining bioavailability of such drugs in food‐effect studies, reference intravenous groups should be included to separate true increase in bioavailability from the effects of decreased clearance. © 2002 Wiley‐Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:1817–1826, 2002
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The Influence of Lipids on Stereoselective Pharmacokinetics of Halofantrine: Important Implications in Food‐Effect Studies Involving Drugs That Bind to Lipoproteins
Journal of Pharmaceutical Sciences, 2002Co-Authors: Dion R. Brocks, Kishor M. WasanAbstract:The objective of this study was to determine the effect of lipids on the pharmacokinetics of Halofantrine enantiomers. Rats were given (+/-)-Halofantrine HCl 2 mg/kg i.v., or 7 mg/kg orally. Some rats were rendered hyperlipidemic by intraperitoneal administration of poloxamer 407 1 g/kg, followed by (+/-)-Halofantrine HCl intravenously. In other normolipidemic rats, (+/-)-Halofantrine was administered under fasted conditions, or after peanut oil given orally. Halofantrine enantiomer plasma concentrations were considerably (>10-fold) increased in hyperlipidemia. Decreases were noted in the clearance, volume of distribution and the unbound fraction in plasma of the hyperlipidemic rats. Peanut oil caused a significant 28% reduction in clearance of the (-), but not the (+) enantiomer (mean clearance reduced 11%) of Halofantrine. After oral Halofantrine, peanut oil resulted in a two- to threefold increase in the plasma area under the curves of Halofantrine enantiomers. Halofantrine enantiomer pharmacokinetics are highly dependent upon plasma lipid concentrations. Oral lipids may result in a stereoselective interaction at the level of clearance. Because lipids may affect clearance of drugs that bind to lipoproteins, in determining bioavailability of such drugs in food-effect studies, reference intravenous groups should be included to separate true increase in bioavailability from the effects of decreased clearance.
Kishor M. Wasan - One of the best experts on this subject based on the ideXlab platform.
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the influence of lipids on stereoselective pharmacokinetics of Halofantrine important implications in food effect studies involving drugs that bind to lipoproteins
Journal of Pharmaceutical Sciences, 2002Co-Authors: Dion R. Brocks, Kishor M. WasanAbstract:Abstract The objective of this study was to determine the effect of lipids on the pharmacokinetics of Halofantrine enantiomers. Rats were given (±)‐Halofantrine HCl 2 mg/kg i.v., or 7 mg/kg orally. Some rats were rendered hyperlipidemic by intraperitoneal administration of poloxamer 407 1 g/kg, followed by (±)‐Halofantrine HCl intravenously. In other normolipidemic rats, (±)‐Halofantrine was administered under fasted conditions, or after peanut oil given orally. Halofantrine enantiomer plasma concentrations were considerably (>10‐fold) increased in hyperlipidemia. Decreases were noted in the clearance, volume of distribution and the unbound fraction in plasma of the hyperlipidemic rats. Peanut oil caused a significant 28% reduction in clearance of the (−), but not the (+) enantiomer (mean clearance reduced 11%) of Halofantrine. After oral Halofantrine, peanut oil resulted in a two‐ to threefold increase in the plasma area under the curves of Halofantrine enantiomers. Halofantrine enantiomer pharmacokinetics are highly dependent upon plasma lipid concentrations. Oral lipids may result in a stereoselective interaction at the level of clearance. Because lipids may affect clearance of drugs that bind to lipoproteins, in determining bioavailability of such drugs in food‐effect studies, reference intravenous groups should be included to separate true increase in bioavailability from the effects of decreased clearance. © 2002 Wiley‐Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:1817–1826, 2002
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the influence of lipids on stereoselective pharmacokinetics of Halofantrine important implications in food effect studies involving drugs that bind to lipoproteins
Journal of Pharmaceutical Sciences, 2002Co-Authors: Dion R. Brocks, Kishor M. WasanAbstract:The objective of this study was to determine the effect of lipids on the pharmacokinetics of Halofantrine enantiomers. Rats were given (+/-)-Halofantrine HCl 2 mg/kg i.v., or 7 mg/kg orally. Some rats were rendered hyperlipidemic by intraperitoneal administration of poloxamer 407 1 g/kg, followed by (+/-)-Halofantrine HCl intravenously. In other normolipidemic rats, (+/-)-Halofantrine was administered under fasted conditions, or after peanut oil given orally. Halofantrine enantiomer plasma concentrations were considerably (>10-fold) increased in hyperlipidemia. Decreases were noted in the clearance, volume of distribution and the unbound fraction in plasma of the hyperlipidemic rats. Peanut oil caused a significant 28% reduction in clearance of the (-), but not the (+) enantiomer (mean clearance reduced 11%) of Halofantrine. After oral Halofantrine, peanut oil resulted in a two- to threefold increase in the plasma area under the curves of Halofantrine enantiomers. Halofantrine enantiomer pharmacokinetics are highly dependent upon plasma lipid concentrations. Oral lipids may result in a stereoselective interaction at the level of clearance. Because lipids may affect clearance of drugs that bind to lipoproteins, in determining bioavailability of such drugs in food-effect studies, reference intravenous groups should be included to separate true increase in bioavailability from the effects of decreased clearance.
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The Influence of Lipids on Stereoselective Pharmacokinetics of Halofantrine: Important Implications in Food‐Effect Studies Involving Drugs That Bind to Lipoproteins
Journal of Pharmaceutical Sciences, 2002Co-Authors: Dion R. Brocks, Kishor M. WasanAbstract:The objective of this study was to determine the effect of lipids on the pharmacokinetics of Halofantrine enantiomers. Rats were given (+/-)-Halofantrine HCl 2 mg/kg i.v., or 7 mg/kg orally. Some rats were rendered hyperlipidemic by intraperitoneal administration of poloxamer 407 1 g/kg, followed by (+/-)-Halofantrine HCl intravenously. In other normolipidemic rats, (+/-)-Halofantrine was administered under fasted conditions, or after peanut oil given orally. Halofantrine enantiomer plasma concentrations were considerably (>10-fold) increased in hyperlipidemia. Decreases were noted in the clearance, volume of distribution and the unbound fraction in plasma of the hyperlipidemic rats. Peanut oil caused a significant 28% reduction in clearance of the (-), but not the (+) enantiomer (mean clearance reduced 11%) of Halofantrine. After oral Halofantrine, peanut oil resulted in a two- to threefold increase in the plasma area under the curves of Halofantrine enantiomers. Halofantrine enantiomer pharmacokinetics are highly dependent upon plasma lipid concentrations. Oral lipids may result in a stereoselective interaction at the level of clearance. Because lipids may affect clearance of drugs that bind to lipoproteins, in determining bioavailability of such drugs in food-effect studies, reference intravenous groups should be included to separate true increase in bioavailability from the effects of decreased clearance.
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the stereoselective distribution of Halofantrine enantiomers within human dog and rat plasma lipoproteins
Pharmaceutical Research, 2000Co-Authors: Dion R. Brocks, Manisha Ramaswamy, Aaron I Macinnes, Kishor M. WasanAbstract:Purpose. To study the in vitro distribution of the enantiomers of theantimalarial drug Halofantrine in human, dog and rat plasmalipoprotein-fractions.Methods. Plasma was spiked with racemic Halofantrine (1000 ng/ml)and incubated for 1 h at 37°C. The fractions (high and low densitylipoproteins, triglyceride-rich lipoproteins and lipoprotein deficientplasma) were separated using density gradient ultracentrifugation.Fractions were assayed for Halofantrine enantiomer using stereospecifichigh performance liquid chromatography.Results. The (−) enantiomer of Halofantrine displayed higher affinityfor the lipoprotein-deficient fraction than the (+) enantiomer in allthree species. The (+) enantiomer was predominately located in thelipoprotein rich fractions of dog and human plasma (the (+):(−) ratioranging from 1.2–9.6). In contrast, the (+):(−) ratio was consistently<1 in lipoprotein-deficient fractions. Dog displayed a large magnitudeof stereoselectivity in Halofantrine distribution to the plasma fractionstested. There were substantial interspecies differences in the pattern ofdistribution of Halofantrine enantiomers within the different fractions. Asignificant positive relationship was observed between Halofantrineuptake into lipoprotein-rich fractions and the percent of apolar corelipid in those fractions. There was also a strong negative correlationbetween total protein concentration and the enantiomeric ratio in thelipoprotein-deficient plasma fraction.Conclusion. Distribution of Halofantrine enantiomer to plasma lipoprotein-fractions is stereoselective and species specific. This differentialbinding of Halofantrine enantiomers to lipoproteins may need to beconsidered in viewing pharmacokinetic and pharmacodynamic datainvolving the drug.
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The stereoselective distribution of Halofantrine enantiomers within human, dog, and rat plasma lipoproteins.
Pharmaceutical Research, 2000Co-Authors: Dion R. Brocks, Manisha Ramaswamy, Aaron I Macinnes, Kishor M. WasanAbstract:Purpose. To study the in vitro distribution of the enantiomers of theantimalarial drug Halofantrine in human, dog and rat plasmalipoprotein-fractions.Methods. Plasma was spiked with racemic Halofantrine (1000 ng/ml)and incubated for 1 h at 37°C. The fractions (high and low densitylipoproteins, triglyceride-rich lipoproteins and lipoprotein deficientplasma) were separated using density gradient ultracentrifugation.Fractions were assayed for Halofantrine enantiomer using stereospecifichigh performance liquid chromatography.Results. The (−) enantiomer of Halofantrine displayed higher affinityfor the lipoprotein-deficient fraction than the (+) enantiomer in allthree species. The (+) enantiomer was predominately located in thelipoprotein rich fractions of dog and human plasma (the (+):(−) ratioranging from 1.2–9.6). In contrast, the (+):(−) ratio was consistently
L. K. Basco - One of the best experts on this subject based on the ideXlab platform.
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Clinical efficacy and pharmacokinetics of micronized Halofantrine for the treatment of acute uncomplicated falciparum malaria in nonimmune patients.
The American Journal of Tropical Medicine and Hygiene, 1994Co-Authors: Olivier Bouchaud, L. K. Basco, J. Le Bras, C. Gillotin, François Gimenez, Robert Farinotti, O. Ramiliarisoa, B. Genissel, Elisabeth Bouvet, Jean-pierre CoulaudAbstract:Twenty-eight nonimmune patients with acute uncomplicated falciparum malaria returning from subSaharan Africa were treated with a micronized formulation of Halofantrine hydrochloride (three doses of 250 mg at 6-hr intervals) to investigate the drug's efficacy, tolerance, and pharmacokinetics. In vitro drug susceptibility patterns were determined by the isotopic semimicrotest. Twenty-four of 28 patients were cured. Two of the four patients experiencing recrudescence were associated with low absorption of the drug and parasites susceptible in vitro to Halofantrine. The other two patients had adequate plasma concentrations of Halofantrine and its main human metabolite, N-desbutylHalofantrine, but the isolates were also resistant in vitro to the drugs, suggesting drug resistance as the cause of treatment failure. Only mild, transitory side effects were noted. A wide interindividual variation in plasma concentrations of Halofantrine and its metabolite was observed. Pharmacokinetic studies suggested that the micronized formulation of Halofantrine hydrochloride may not increase drug absorption considerably. Further studies using higher doses or longer treatment periods are needed to ensure that adequate plasma concentrations of the drug are used.
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Plasma concentrations of the enantiomers of Halofantrine and its main metabolite in malaria patients.
European Journal of Clinical Pharmacology, 1994Co-Authors: François Gimenez, L. K. Basco, J. Le Bras, C. Gillotin, Olivier Bouchaud, A. F. Aubry, Irving W. Wainer, Robert FarinottiAbstract:The plasma concentrations of the enantiomers of Halofantrine and its N-desbutyl metabolite in six patients with malaria were measured after oral administration of 3×750 mg doses of micronised, racemic Halofantrine hydrochloride given at 6-hour intervals. Significant differences were observed between the plasma concentrations of the enantiomers both of Halofantrine and its N-monodesbutyl metabolite. AUC084h values were higher for (+)Halofantrine (9917 μg·ml−1·h) than for (-)-Halofantrine (6127 μg·ml−1·h). The clinical significance of these observations is not known. The isomers have equipotent activity in vitro but their relative toxicity has not yet been assessed.
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In vitro activity of the enantiomers of N-desbutyl derivative of Halofantrine
Tropical medicine and parasitology : official organ of Deutsche Tropenmedizinische Gesellschaft and of Deutsche Gesellschaft fur Technische Zusammenar, 1994Co-Authors: L. K. Basco, François Gimenez, Robert Farinotti, B. Genissel, G. Peytavin, J. Le BrasAbstract:The in vitro activity of the enantiomers of N-desbutylHalofantrine, the major human metabolite of Halofantrine, was compared using the semi-microtest against the multidrug-resistant Plasmodium falciparum FCM 29/Cameroon clone. The mean 50% inhibitory concentration (IC50) values (+/- standard deviation) of the enantiomers were equivalent (2.07 +/- 0.41 and 1.70 +/- 0.33 nmol/L). The enantiomers of the metabolite of Halofantrine, as well as those of the parent compound, have the same antimalarial activity. Since (+)-Halofantrine and enantiomer-1 of the metabolite attain higher plasma concentrations in man, our study suggests that these enantiomers may be more active in vivo.
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in vitro activity of Halofantrine and its relationship to other standard antimalarial drugs against african isolates and clones of plasmodium falciparum
American Journal of Tropical Medicine and Hygiene, 1992Co-Authors: L. K. Basco, Le J BrasAbstract:Abstract The in vitro activity of Halofantrine was studied in chloroquine-susceptible and chloroquine-resistant African clones of Plasmodium falciparum over a period of six months. The susceptibility level remained stable in both clones. The chloroquine-susceptible clone (50% inhibitory concentration [IC50] 6.88 nM) was less susceptible to Halofantrine than the chloroquine-resistant clone (IC50 2.98 nM). Using an isotopic semimicro drug susceptibility test, the in vitro activity of Halofantrine was compared with the activities of chloroquine, quinine, and mefloquine to study the cross-resistance patterns against 76 African isolates of P. falciparum isolated from cases of malaria imported into France. Chloroquine-resistant isolates (n = 47) were significantly less susceptible to quinine (IC50 234 nM), but were more susceptible to both mefloquine (IC50 3.20 nM) and Halofantrine (IC50 1.14 nM) compared with the chloroquine-susceptible isolates (n = 29; IC50 147 nM for quinine, 7.16 nM for mefloquine, and 2.62 nM for Halofantrine). A significant positive correlation was found between the activities of chloroquine and quinine and between those of mefloquine and Halofantrine, indicating cross-resistance between these drugs, while a negative correlation was observed between chloroquine and mefloquine or Halofantrine. The responses to quinine and mefloquine or Halofantrine showed no correlation with each other. These results reinforce the importance of a cautious use of antimalarial drugs in Africa.
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In vitro activity of the enantiomers of mefloquine, Halofantrine and enpiroline against Plasmodium falciparum.
British Journal of Clinical Pharmacology, 1992Co-Authors: L. K. Basco, C. Gillotin, François Gimenez, Robert Farinotti, J. Le BrasAbstract:The in vitro activity of the enantiomers of mefloquine, Halofantrine and enpiroline was compared against chloroquine-resistant and -susceptible strains of Plasmodium falciparum using a semi-micro drug susceptibility test. For each strain, the corresponding enantiomers exhibited similar activities. The enantiomers of Halofantrine were the most active against both susceptible and resistant strains, followed by the enantiomers of mefloquine and enpiroline.
Walter R J Taylor - One of the best experts on this subject based on the ideXlab platform.
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Short report: in vivo sensitivity of Plasmodium falciparum to Halofantrine in southern central Vietnam.
The American Journal of Tropical Medicine and Hygiene, 2003Co-Authors: Doan Hanh Nhan, Walter R J Taylor, David J Fryauff, Nguyen Dieu Thuong, Tran Thi Uyen, Ika Susanti, Eduardo Gómez-saladín, Le Dinh Cong, J K BairdAbstract:Drug-resistant Plasmodium falciparum is present in Vietnam. We assessed the in vivo sensitivity of P. falciparum to Halofantrine in two villages in the southern part of central Vietnam. Halofantrine (8 mg/kg × 3 doses) was administered to 37 patients with either P. falciparum (n 32) or mixed P. falciparum/P. vivax malaria (n 5). End points were parasite sensitivity or resistance (RI/RII/RIII) determined by parasite clearance, persistence, or recurrence during 28 days of follow-up. By day 28, 31 (93.9%) of 33 (95% confidence interval 79.8�99.2%) patients were sensitive. Two patients had recurrent P. falciparum parasitemia on days 14 and 21. Halofantrine effectively treated uncomplicated P. falciparum malaria in these Vietnamese patients.
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assessing drug sensitivity of plasmodium vivax to Halofantrine or choroquine in southern central vietnam using an extended 28 day in vivo test and polymerase chain reaction genotyping
American Journal of Tropical Medicine and Hygiene, 2000Co-Authors: Walter R J Taylor, H N Doan, D T Nguyen, T U Tran, David J Fryauff, Eduardo Gomezsaladin, Kevin C Kain, J K BairdAbstract:Chloroquine-resistant Plasmodium vivax malaria is emerging in Oceania, Asia, and Latin America. We assessed the drug sensitivity of P. vivax to chloroquine or Halofantrine in two villages in southern, central Vietnam. This area has chloroquine-resistant Plasmodium falciparum but no documented chloroquine-resistant P. vivax. Standard dose chloroquine (25 mg/kg, over 48 hours) or Halofantrine (8 mg/kg, 3 doses) was administered to 29 and 25 patients, respectively. End points were parasite sensitivity or resistance determined at 28 days. Of the evaluable patients, 23/23 100% (95% confidence interval [CI] 85.1-100) chloroquine and 21/24 (87.5%) (95% CI 67.6-97.3) Halofantrine-treated patients were sensitive. Three Halofantrine recipients had initial clearance but subsequent recurrence of their parasitemias. Genotyping of the recurrent and Day 0 parasitemias differed, suggesting either new infections or relapses of liver hypnozoites from antecedent infections. Among these Vietnamese patients, P. vivax was sensitive to chloroquine and Halofantrine. Genotyping was useful for differentiating the recurrent vivax parasitemias.
