Plasma levels of praziquantel decrease when dexamethasone is given simultaneously

Vázquez, María López; Jung, Helgi; Sotelo, Julio

doi:10.1212/wnl.37.9.1561

Cited by 135 publications

(51 citation statements)

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“…Statistically significant differences were found in C max and AUC 0-8 between treatments, as well as in the MRT (P Ͻ 0.05); however, plasma elimination half-lives were similar to each other and comparable to those obtained previously (3,9). When preprandial and postprandial data were compared, there were no statistically significant differences with respect to T max or to elimination half-lives.…”

supporting

confidence: 77%

Bioavailability of Praziquantel Increases with Concomitant Administration of Food

Castro

Medina

Sotelo

et al. 2000

Antimicrob Agents Chemother

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In the present study we found that after a single oral dose of 1,800 mg of praziquantel, following a high-lipid diet and a high-carbohydrate diet, the maximum levels in plasma increased 243 and 515% and the area under the plasma concentration curve from 0 to 8 h increased 180 and 271%, respectively.Nine healthy volunteers participated in the study. The mean age was 33.44 years (range, 26 to 47 years), and the mean weight was 72.22 Ϯ 11.29 kg. The protocol was approved by the local ethics committee, and informed written consent was obtained from each subject after detailed explanation of the purpose and risks of the study. Subjects did not take any other medication or alcohol for at least 15 days prior to the study.Volunteers were randomly separated into three groups of three subjects each. Group I received three tablets of 600 mg of praziquantel (1,800 mg) after 10 h of fasting; group II received the same dose of praziquantel immediately after administration of a high-fat diet, and group III received the same dose of praziquantel after a high-carbohydrate diet. Volunteers received a standard lunch 4 h after drug ingestion. The study was repeated in a crossover design allowing 1 week of washout between treatments. Blood samples were obtained through an indwelling catheter placed in the antecubital vein 0.0, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, and 8.0 h after the drug administration. Samples were centrifuged; the plasma was separated and stored at Ϫ4°C until analysis.The high-fat diet consisted of two fried eggs, one slice of ham, orange juice, and milk (200 ml) (protein, 19.63%; fat, 32.44%; and carbohydrate, 47.91%; 656 cal); the high-carbohydrate diet consisted of four tortillas, tomato, chicken (100 g), a slice of white bread, and a glass (200 ml) of orange juice (protein, 15.30%; fat, 10.54%, and carbohydrate, 74.15%; 674.5 cal).Praziquantel in plasma was determined using a high-performance liquid chromatography assay as previously reported (1). The method was linear from 15.6 to 8,000 ng/ml. The limit of quantitation was 15.6 ng/ml. The maximum within-day coefficient of variation was 7.9% at 15.6 ng/ml, and the mean value FIG. 1. Mean concentration in plasma (ϩstandard error of the mean) of praziquantel in healthy volunteers treated with a single oral dose of 1,800 mg (three tablets of 600 mg) during fasting (F) or immediately after a high-fat (‚) or a high-carbohydrate (s) breakfast.

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supporting

confidence: 77%

Bioavailability of Praziquantel Increases with Concomitant Administration of Food

Castro

Medina

Sotelo

et al. 2000

Antimicrob Agents Chemother

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“…For example, coadministration of CYP 3A4 inducers such as dexamethasone dramatically reduces plasma PZQ levels in patients with neurocysticercosis (6,31,32). Albendazole is an inhibitor of CYP enzymes, and when it is administered concomitantly with PZQ, plasma R-PZQ levels are increased (16).…”

Section: Fig 2 Examples Of Heat Production Recorded By Microcalorimetmentioning

confidence: 99%

Activity of Praziquantel Enantiomers and Main Metabolites against Schistosoma mansoni

Meister

Ingram-Sieber

Cowan

et al. 2014

Antimicrob Agents Chemother

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A racemic mixture of R and S enantiomers of praziquantel (PZQ) is currently the treatment of choice for schistosomiasis. Though the S enantiomer and the metabolites are presumed to contribute only a little to the activity of the drug, in-depth sideby-side studies are lacking. The aim of this study was to investigate the in vitro activities of PZQ and its main metabolites, namely, R-and S-cis-and R-and S-trans-4=-hydroxypraziquantel, against adult worms and newly transformed schistosomula (NTS). Additionally, we explored the in vivo activity and hepatic shift (i.e., the migration of the worms to the liver) produced by each PZQ enantiomer in mice. Fifty percent inhibitory concentrations of R-PZQ, S-PZQ, and R-trans-and R-cis-4=-hydroxypraziquantel of 0.02, 5.85, 4.08, and 2.42 g/ml, respectively, for adult S. mansoni were determined in vitro. S-trans-and S-cis-4=-hydroxypraziquantel were not active at 100 g/ml. These results are consistent with microcalorimetry data and studies with NTS. In vivo, single 400-mg/kg oral doses of R-PZQ and S-PZQ achieved worm burden reductions of 100 and 19%, respectively. Moreover, worms treated in vivo with S-PZQ displayed an only transient hepatic shift and returned to the mesenteric veins within 24 h. Our data confirm that R-PZQ is the main effector molecule, while S-PZQ and the metabolites do not play a significant role in the antischistosomal properties of PZQ. S chistosomiasis or bilharzia is caused by blood flukes of the genus Schistosoma and is part of the group of neglected tropical diseases affecting more than 207 million people in tropical areas (1-3).The exclusive treatment to date for schistosomiasis is praziquantel (PZQ), which was discovered in the 1970s by Merck and Bayer. PZQ is administered as a racemic mixture of R and S enantiomers in tablets of 600 mg. The recommended dosage to treat schistosomiasis is 20 mg/kg three times in 1 day, and since PZQ does not act on juvenile worms, follow-up treatment 4 to 6 weeks later is strongly advised (4). In preventive chemotherapy programs, PZQ is administered as a single 40-mg/kg dose to at-risk populations (5). PZQ undergoes significant first-pass metabolism through the liver enzyme cytochrome P450 (CYP) 3A4 and to a lesser extent through 1A2 and 2C19 (6). R-PZQ is metabolized at a much higher rate than S-PZQ. R-PZQ is transformed mainly into cis-and trans-hydroxypraziquantel (4-OH-PZQ), while S-PZQ is converted to other monohydroxylated metabolites. In rat liver microsomes, the main metabolite is cis-4-OH-PZQ (7, 8), while in humans it is trans-4-OH-PZQ (9).The difference in the antischistosomal activity of each PZQ enantiomer has been known since 1983 (10), and several studies have observed greater activity of R-PZQ than of S-PZQ in vitro and in vivo (11)(12)(13). A clinical trial with Schistosoma japonicuminfected patients also recorded a higher efficacy of R-PZQ than of racemic PZQ at the same dosage (14, 15). Additionally, treatment with R-PZQ resulted in fewer adverse events than the standard treatment (14). However, ...

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“…For this reason, both albendazole and praziquantel are generally given simultaneously with steroids in order to control the edema and intracranial hypertension that may occur as a result of therapy. Praziquantel interacts with steroids, decreasing its serum concentrations (105), although there is no evidence that this pharmacological interaction affects its parasiticidal properties. Serum levels of phenytoin and carbamazepine may also be lowered as the result of simultaneous praziquantel administration (12).…”

Section: Vol 15 2002 Guidelines For Treatment Of Neurocysticercosismentioning

confidence: 99%

Current Consensus Guidelines for Treatment of Neurocysticercosis

et al. 2002

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Taenia solium neurocysticercosis is a common cause of epileptic seizures and other neurological morbidity in most developing countries. It is also an increasingly common diagnosis in industrialized countries because of immigration from areas where it is endemic. Its clinical manifestations are highly variable and depend on the number, stage, and size of the lesions and the host's immune response. In part due to this variability, major discrepancies exist in the treatment of neurocysticercosis. A panel of experts in taeniasis/cysticercosis discussed the evidence on treatment of neurocysticercosis for each clinical presentation, and we present the panel's consensus and areas of disagreement. Overall, four general recommendations were made: (i) individualize therapeutic decisions, including whether to use antiparasitic drugs, based on the number, location, and viability of the parasites within the nervous system; (ii) actively manage growing cysticerci either with antiparasitic drugs or surgical excision; (iii) prioritize the management of intracranial hypertension secondary to neurocysticercosis before considering any other form of therapy; and (iv) manage seizures as done for seizures due to other causes of secondary seizures (remote symptomatic seizures) because they are due to an organic focus that has been present for a long time

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Plasma levels of praziquantel decrease when dexamethasone is given simultaneously

Cited by 135 publications

References 0 publications

Bioavailability of Praziquantel Increases with Concomitant Administration of Food

Bioavailability of Praziquantel Increases with Concomitant Administration of Food

Activity of Praziquantel Enantiomers and Main Metabolites against Schistosoma mansoni

Current Consensus Guidelines for Treatment of Neurocysticercosis

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