Enantioselective kinetic disposition of albendazole sulfoxide in patients with neurocysticercosis

Marques, Maria Paula Da Costa; Takayanagui, Osvaldo Massaiti; Bonato, Pierina Sueli; Santos, Sílvia Regina Cavani Jorge; Lanchote, Vera Lúcia

doi:10.1002/(sici)1520-636x(1999)11:3<218::aid-chir8>3.0.co;2-g

Cited by 32 publications

(22 citation statements)

References 18 publications

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“…After intestinal absorption, ALB is rapidly converted into the active metabolite ASOX, an enantimeric mixture of (+)-ASOX and (−)-ASOX [60][61][62]. Plasma concentrations of the (+)-ASOX enantiomer are approximately nine-times higher than those observed for the (−)-ASOX antipode [52]. ASOX is also found in the CSF at a high proportion (a 2:1 serum to CSF ratio) [26].…”

Section: Failure Of Anticysticercal Therapy: Possible Explanationsmentioning

confidence: 98%

“…First, there is considerable inter-individual variability in the plasma concentration of PZQ and ASOX [26,52,53]. The exact mechanism of this variability in the plasma concentration of the drug is not clear but may include a gender factor -greater ASOX concentration in women than in men -and dominant expression of cytochrome P450 isoforms [54,55].…”

Section: Failure Of Anticysticercal Therapy: Possible Explanationsmentioning

confidence: 99%

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Therapy for neurocysticercosis

Takayanagui

2004

Expert Review of Neurotherapeutics

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Section: Failure Of Anticysticercal Therapy: Possible Explanationsmentioning

confidence: 98%

Section: Failure Of Anticysticercal Therapy: Possible Explanationsmentioning

confidence: 99%

Therapy for neurocysticercosis

Takayanagui

2004

Expert Review of Neurotherapeutics

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“…The two possible enantiomers, (ϩ)-(R)-and (Ϫ)-(S)-ABZSO (13), show different pharmacokinetics and affinities for cytosolic proteins from different parasites (28). Kinetic parameters of (ϩ)-(R)-and (Ϫ)-(S)-ABZSO enantiomers in NCC patients treated with ABZ differ in renal excretion (14), accumulation in plasma (15), and, most importantly, distribution in the cerebrospinal fluid (12). Even though the levels of effectiveness of the two enantiomers against a number of other helminths differ, the effect of the isolated enantiomers against T. solium metacestodes (cysts) has not been reported.…”

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confidence: 99%

In Vitro Analysis of Albendazole Sulfoxide Enantiomers Shows that (+)-( R )-Albendazole Sulfoxide Is the Active Enantiomer against Taenia solium

Paredes

Lourenço

Marzal

et al. 2013

Antimicrob Agents Chemother

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Albendazole is an anthelmintic drug widely used in the treatment of neurocysticercosis (NCC), an infection of the brain with Taenia N eurocysticercosis (NCC) is a major cause of adult-onset seizures and epilepsy in many areas of the developing world. It is an infection with the larval cyst form of the cestode tapeworm Taenia solium acquired through the accidental ingestion of ova shed in the feces of human tapeworm carriers. The released oncospheres find their way to the bloodstream and are carried throughout the body but develop mostly in the muscles, subcutaneous tissues, and brain. Almost all the symptoms are due to brain involvement (1).Two drugs, the benzimidazole albendazole (ABZ) and the pyrazinoisoquinoline praziquantel (PZQ), are commonly used to treat neurocysticercosis, usually with accompanying immunosuppressive/anti-inflammatory medication (2-4). Albendazole is frequently preferred to praziquantel because it is more widely available, has a lower cost, and normally requires shorter courses of treatment (and hence represents lower hospitalization-associated expenses) for higher efficacy (2, 5-7).In susceptible parasites, the main effect of ABZ is the inhibition of tubulin polymerization into microtubules, but the drug also causes biochemical changes such as inhibition of mitochondrial fumarate reductase, reduced glucose transport, and uncoupling of oxidative phosphorylation, impairing ATP generation (8, 9). Although ABZ has been used since the 1970s (10, 11), it is not completely effective in killing cysts; 12% and 45% of total cysts remain after the usual dosing regimens used with albendazole and praziquantel, respectively (12). Cure rates are unacceptably low for both drugs at about 40% to 50%, so retreatments are often required.After oral administration, the nonchiral ABZ is oxidized in the liver to its active metabolite, albendazole sulfoxide (ABZSO), with one chiral center in the sulfoxide group. The two possible enan- (13), show different pharmacokinetics and affinities for cytosolic proteins from different parasites (28). Kinetic parameters of (ϩ)-(R)-and (Ϫ)-(S)-ABZSO enantiomers in NCC patients treated with ABZ differ in renal excretion (14), accumulation in plasma (15), and, most importantly, distribution in the cerebrospinal fluid (12). Even though the levels of effectiveness of the two enantiomers against a number of other helminths differ, the effect of the isolated enantiomers against T. solium metacestodes (cysts) has not been reported. tiomers, (ϩ)-(R)-and (Ϫ)-(S)-ABZSOA sensitive in vitro system to quantify drug effects on cysts of T. solium has been recently reported (16). In this system, drug sensitivity to both ABZSO and PZQ correlates with the degree of inhibition of alkaline phosphatase (AP) release from cysts, obtained from naturally infected pigs and cultured in vitro (16). Using this system, we compared the anthelmintic effect of the (ϩ)-(R)-and (Ϫ)-(S)-ABZSO enantiomers to effects of the ABZSO racemic mixture and of PZQ. Here we show that the antiparasitic effect of the drug ...

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“…25 The chiral separation of albendazole sulfoxide was Due to its extensive metabolism, albendazole is not detected in plasma samples, and therefore, pharmacokinetic studies are carried out by quantification of the active metabolite.…”

Section: Resultsmentioning

confidence: 99%

CHIRAL CAPILLARY ELECTROPHORETIC SEPARATION OF SELECTED DRUGS AND METABOLITES USING SULFATED Β-Cyclodextrin

Bonato

Jabor

Paias

et al. 2001

Journal of Liquid Chromatography & Related Technologies

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In this paper, we report the chiral separation of some drugs and their metabolites using sulfated β-cyclodextrin, a powerful chiral selector that has proven to be highly efficient for the separation of chiral drugs, alone or in combination, with other chiral additives. Praziquantel, its metabolite trans-4-hydroxypraziquantel, and albendazole sulfoxide are neutral compounds and could be separated at basic pH (8-10).The simultaneous chiral separation of praziquantel and its metabolite enantiomers was only possible by the addition of sodium deoxycholate to the running buffer. Fluoxetine, disopyramide, and mexiletine, as well as their metabolites are basic com-pounds and were separated by appropriate selection of the running buffer pH and CD concentration. In addition, the effects of the experimental parameters, such as concentration of sulfated βcyclodextrin, pH and buffer concentration, temperature, and voltage were also evaluated.Among the several parameters studied, the concentration of the chiral selector and the pH were the most important to obtain the chiral separation of the selected drugs and metabolites.

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Enantioselective kinetic disposition of albendazole sulfoxide in patients with neurocysticercosis

Cited by 32 publications

References 18 publications

Therapy for neurocysticercosis

Therapy for neurocysticercosis

In Vitro Analysis of Albendazole Sulfoxide Enantiomers Shows that (+)-( R )-Albendazole Sulfoxide Is the Active Enantiomer against Taenia solium

CHIRAL CAPILLARY ELECTROPHORETIC SEPARATION OF SELECTED DRUGS AND METABOLITES USING SULFATED Β-Cyclodextrin

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