scholarly journals Pharmacokinetics of Amodiaquine and Desethylamodiaquine in Pregnant and Postpartum Women with Plasmodium vivax Malaria

2011 ◽  
Vol 55 (9) ◽  
pp. 4338-4342 ◽  
Author(s):  
Marcus J. Rijken ◽  
Rose McGready ◽  
Vincent Jullien ◽  
Joel Tarning ◽  
Niklas Lindegardh ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Dosing Regimen ◽  
Noncompartmental Analysis ◽  
Time Data ◽  
Content Type ◽  
Concentration Time ◽  
Chromatography Tandem Mass Spectrometry ◽  
Pharmacokinetic Properties ◽  
Plasmodium Vivax Malaria ◽  
Liquid Chromatography Tandem Mass

ABSTRACTIn order to study the pharmacokinetic properties of amodiaquine and desethylamodiaquine during pregnancy, 24 pregnant women in the second and third trimesters of pregnancy and withPlasmodium vivaxmalaria were treated with amodiaquine (10 mg/kg of body weight/day) for 3 days. The same women were studied again at 3 months postpartum. Plasma was analyzed for amodiaquine and desethylamodiaquine by use of a liquid chromatography-tandem mass spectrometry method. Individual concentration-time data were evaluated using noncompartmental analysis. There were no clinically relevant differences in the pharmacokinetics of amodiaquine and desethylamodiaquine between pregnant (n= 24) and postpartum (n= 18) women. The results suggest that the current amodiaquine dosing regimen is adequate for the treatment ofP. vivaxinfections during pregnancy.

Simultaneous determination of 1,3-dicaffeoylquinic acid and caffeic acid in rat plasma by liquid chromatography/tandem mass spectrometry and its application to a pharmacokinetic study

2015 ◽  
Vol 7 (8) ◽  
pp. 3587-3592 ◽  
Author(s):  
Guoliang Dai ◽  
Shitang Ma ◽  
Bingting Sun ◽  
Tao Gong ◽  
Shijia Liu ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Plasma Concentration ◽  
Rat Plasma ◽  
Tandem Mass ◽  
Concentration Time ◽  
Chromatography Tandem Mass Spectrometry ◽  
Dicaffeoylquinic Acid ◽  
Liquid Chromatography Tandem Mass

The figure shows the average plasma concentration–time curves after an intravenous administration of 4 mL kg−1 Dengzhanxixin injection to rats.

scholarly journals Prospective Study of Plasmodium vivax Malaria Recurrence after Radical Treatment with a Chloroquine-Primaquine Standard Regimen in Turbo, Colombia

2016 ◽  
Vol 60 (8) ◽  
pp. 4610-4619 ◽  
Author(s):  
Lina Zuluaga-Idárraga ◽  
Silvia Blair ◽  
Sheila Akinyi Okoth ◽  
Venkatachalam Udhayakumar ◽  
Paula L. Marcet ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Standard Regimen ◽  
High Genetic Diversity ◽  
Content Type ◽  
Longitudinal Observational Study ◽  
High Incidence ◽  
Plasmodium Vivax Malaria ◽  
Previous Infection ◽  
First Recurrence ◽  
Infection Episode

ABSTRACTPlasmodium vivaxrecurrences help maintain malaria transmission. They are caused by recrudescence, reinfection, or relapse, which are not easily differentiated. A longitudinal observational study took place in Turbo municipality, Colombia. Participants with uncomplicatedP. vivaxinfection received supervised treatment concomitantly with 25 mg/kg chloroquine and 0.25 mg/kg/day primaquine for 14 days. Incidence of recurrence was assessed over 180 days. Samples were genotyped, and origins of recurrences were established. A total of 134 participants were enrolled between February 2012 and July 2013, and 87 were followed for 180 days, during which 29 recurrences were detected. The cumulative incidence of first recurrence was 24.1% (21/87) (95% confidence interval [CI], 14.6 to 33.7%), and 86% (18/21) of these events occurred between days 51 and 110. High genetic diversity ofP. vivaxstrains was found, and 12.5% (16/128) of the infections were polyclonal. Among detected recurrences, 93.1% (27/29) of strains were genotyped as genetically identical to the strain from the previous infection episode, and 65.5% (19/29) of infections were classified as relapses. Our results indicate that there is a high incidence ofP. vivaxmalaria recurrence after treatment in Turbo municipality, Colombia, and that a large majority of these episodes are likely relapses from the previous infection. We attribute this to the primaquine regimen currently used in Colombia, which may be insufficient to eliminate hypnozoites.

scholarly journals Antibodies to a Single, Conserved Epitope in Anopheles APN1 Inhibit Universal Transmission of Plasmodium falciparum and Plasmodium vivax Malaria

2013 ◽  
Vol 82 (2) ◽  
pp. 818-829 ◽  
Author(s):  
Jennifer S. Armistead ◽  
Isabelle Morlais ◽  
Derrick K. Mathias ◽  
Juliette G. Jardim ◽  
Jaimy Joy ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Plasmodium Vivax ◽  
Content Type ◽  
Block Transmission ◽  
Antibody Recognition ◽  
Protective Epitope ◽  
Product Profile ◽  
Plasmodium Vivax Malaria ◽  
Transmission Blocking Vaccines ◽  
Conserved Epitope

ABSTRACTMalaria transmission-blocking vaccines (TBVs) represent a promising approach for the elimination and eradication of this disease. AnAPN1 is a lead TBV candidate that targets a surface antigen on the midgut of the obligate vector of thePlasmodiumparasite, theAnophelesmosquito. In this study, we demonstrated that antibodies targeting AnAPN1 block transmission ofPlasmodium falciparumandPlasmodium vivaxacross distantly related anopheline species in countries to which malaria is endemic. Using a biochemical and immunological approach, we determined that the mechanism of action for this phenomenon stems from antibody recognition of a single protective epitope on AnAPN1, which we found to be immunogenic in murine and nonhuman primate models and highly conserved among anophelines. These data indicate that AnAPN1 meets the established target product profile for TBVs and suggest a potential key role for an AnAPN1-based panmalaria TBV in the effort to eradicate malaria.

scholarly journals Population Pharmacokinetic and Pharmacodynamic Modeling of Amodiaquine and Desethylamodiaquine in Women with Plasmodium vivax Malaria during and after Pregnancy

2012 ◽  
Vol 56 (11) ◽  
pp. 5764-5773 ◽  
Author(s):  
Joel Tarning ◽  
Palang Chotsiri ◽  
Vincent Jullien ◽  
Marcus J. Rijken ◽  
Martin Bergstrand ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Plasmodium Vivax ◽  
Plasma Concentrations ◽  
Inhibitory Effect ◽  
Biologically Active ◽  
Pharmacodynamic Modeling ◽  
Population Pharmacokinetic ◽  
Content Type ◽  
Plasmodium Vivax Malaria

ABSTRACTAmodiaquine is effective for the treatment ofPlasmodium vivaxmalaria, but there is little information on the pharmacokinetic and pharmacodynamic properties of amodiaquine in pregnant women with malaria. This study evaluated the population pharmacokinetic and pharmacodynamic properties of amodiaquine and its biologically active metabolite, desethylamodiaquine, in pregnant women withP. vivaxinfection and again after delivery. Twenty-seven pregnant women infected withP. vivaxmalaria on the Thai-Myanmar border were treated with amodiaquine monotherapy (10 mg/kg/day) once daily for 3 days. Nineteen women, with and withoutP. vivaxinfections, returned to receive the same amodiaquine dose postpartum. Nonlinear mixed-effects modeling was used to evaluate the population pharmacokinetic and pharmacodynamic properties of amodiaquine and desethylamodiaquine. Amodiaquine plasma concentrations were described accurately by lagged first-order absorption with a two-compartment disposition model followed by a three-compartment disposition of desethylamodiaquine under the assumption of completein vivoconversion. Body weight was implemented as an allometric function on all clearance and volume parameters. Amodiaquine clearance decreased linearly with age, and absorption lag time was reduced in pregnant patients. Recurrent malaria infections in pregnant women were modeled with a time-to-event model consisting of a constant-hazard function with an inhibitory effect of desethylamodiaquine. Amodiaquine treatment reduced the risk of recurrent infections from 22.2% to 7.4% at day 35. In conclusion, pregnancy did not have a clinically relevant impact on the pharmacokinetic properties of amodiaquine or desethylamodiaquine. No dose adjustments are required in pregnancy.

scholarly journals Determinants of primaquine and carboxyprimaquine exposures in children and adults with Plasmodium vivax malaria

2021 ◽  
Author(s):  
Cindy S Chu ◽  
James A Watson ◽  
Aung Pyae Phyo ◽  
Htun Htun Win ◽  
Widi Yotyingaphiram ◽  
...  
Keyword(s):  
Young Children ◽  
Plasmodium Vivax ◽  
Plasma Concentrations ◽  
Radical Cure ◽  
Pharmacokinetic Properties ◽  
Daily Dose ◽  
Plasmodium Vivax Malaria ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
To Receive ◽  
Cyp 2D6

Background Primaquine is the only widely available drug for radical cure of Plasmodium vivax malaria. There is uncertainty whether the pharmacokinetic properties of primaquine are altered significantly in childhood or not. Methods Glucose-6-phosphate dehydrogenase normal patients with uncomplicated P. vivax malaria were randomized to receive either chloroquine (25mg base/kg) or dihydroartemisinin-piperaquine (dihydroartemisinin 7mg/kg and piperaquine 55mg/kg) plus primaquine; given either as 0.5 mg base/kg/day for 14 days or 1 mg/kg/day for 7 days. Pre-dose day 7 venous plasma concentrations of chloroquine, desethylchloroquine, piperaquine, primaquine and carboxyprimaquine were measured. Methemoglobin levels were measured on day 7. Results Day 7 primaquine and carboxyprimaquine concentrations were available for 641 patients. After adjustment for the primaquine mg/kg daily dose, day of sampling, partner drug, and fever clearance, there was a significant non-linear relationship between age and trough primaquine and carboxyprimaquine concentrations, and day methemoglobin levels. Compared to adults 30 years of age, children 5 years of age had trough primaquine concentrations 0.53 (95% CI: 0.39- 0.73) fold lower, trough carboxyprimaquine concentrations 0.45 (95% CI: 0.35- 0.55) fold lower, and day 7 methemoglobin levels 0.87 (95% CI: 0.58-1.27) fold lower. Increasing concentrations of piperaquine and chloroquine and poor metabolizer CYP 2D6 alleles were associated with higher day 7 primaquine and carboxyprimaquine concentrations. Higher blood methemoglobin concentrations were associated with a lower risk of recurrence. Conclusion Young children have lower primaquine and carboxyprimaquine exposures, and lower levels of methemoglobinemia, than adults. Young children may need higher weight adjusted primaquine doses than adults.

scholarly journals Cerebrospinal Fluid Penetration of Ceftolozane-Tazobactam in Critically Ill Patients with an Indwelling External Ventricular Drain

2020 ◽  
Vol 65 (1) ◽  
pp. e01698-20 ◽  
Author(s):  
Fekade B. Sime ◽  
Melissa Lassig-Smith ◽  
Therese Starr ◽  
Janine Stuart ◽  
Saurabh Pandey ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
External Ventricular Drain ◽  
Compartment Model ◽  
Time Data ◽  
Time Curve ◽  
Content Type ◽  
Concentration Time ◽  
Unbound Concentration

ABSTRACTThe aim of this study was to describe the pharmacokinetics of ceftolozane-tazobactam in plasma and cerebrospinal fluid (CSF) of infected critically ill patients. In a prospective observational study, critically ill patients (≥18 years) with an indwelling external ventricular drain received a single intravenous dose of 3.0 g ceftolozane-tazobactam. Serial plasma and CSF samples were collected for measurement of unbound ceftolozane and tazobactam concentration by liquid chromatography. Unbound concentration-time data were modeled in R using Pmetrics. Dosing simulations were performed using the final model. A three-compartment model adequately described the data from 10 patients. For ceftolozane, the median (interquartile range [IQR]) area under the unbound concentration-time curve from time zero to infinity (fAUC0-inf) in the CSF and plasma were 30 (19 to 128) h·mg/liter and 323 (183 to 414) h·mg/liter, respectively. For tazobactam, these values were 5.6 (2 to 24) h·mg/liter and 52 (36 to 80) h·mg/liter, respectively. Mean ± standard deviation (SD) CSF penetration ratios were 0.2 ± 0.2 and 0.2 ± 0.26 for ceftolozane and tazobactam, respectively. With the regimen of 3.0 g every 8 h, a probability of target attainment (PTA) of ≥0.9 for 40% fT>MIC in the CSF was possible only when MICs were ≤0.25 mg/liter. The CSF cumulative fractional response for Pseudomonas aeruginosa-susceptible MIC distribution was 73%. The tazobactam PTA for the minimal suggested exposure of 20% fT>1 mg/liter was 12%. The current maximal dose of ceftolozane-tazobactam (3.0 g every 8 h) does not provide adequate CSF exposure for treatment of Gram-negative meningitis or ventriculitis unless the MIC for the causative pathogen is very low (≤0.25 mg/liter).

scholarly journals Identification of the OXA-48 Carbapenemase Family by Use of Tryptic Peptides and Liquid Chromatography-Tandem Mass Spectrometry

2019 ◽  
Vol 57 (5) ◽  
Author(s):  
Jeffrey R. Strich ◽  
Honghui Wang ◽  
Ousmane H. Cissé ◽  
Jung-Ho Youn ◽  
Steven K. Drake ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Tandem Mass Spectrometry ◽  
Accuracy Assessment ◽  
Multiple Reaction Monitoring ◽  
Carbapenem Resistance ◽  
Tandem Mass ◽  
Content Type ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass

ABSTRACT Phenotypic detection of the OXA-48-type class D β-lactamases in Enterobacteriaceae is challenging. We describe a rapid (less than 90 min) assay for the identification of OXA-48 family carbapenemases in subcultured bacterial isolates based on a genoproteomic approach. Following in silico trypsin digestion to ascertain theoretical core peptides common to the OXA-48 family, liquid chromatography-tandem mass spectrometry (LC-MS/MS) data-dependent acquisition was used to identify candidate peptide markers. Two peptides were selected based on performance characteristics: ANQAFLPASTFK, a core peptide common to all 12 OXA-48 family β-lactamase members, and YSVVPVYQEFAR, a highly specific peptide common to 11 of 12 OXA-48 family proteins providing the basis for an LC-MS/MS multiple reaction monitoring assay. An accuracy assessment was performed that included 98 isolates, 26 of which were OXA-48 positive. Two additional specificity assessments were performed including a mixture of isolates positive for OXA-48, KPC, NDM, VIM, and IMP carbapenemases. A combination of expert rules and expert judgment was applied by blinded operators to identify positive isolates. All isolates containing an OXA-48 family carbapenemase across all three test sets were correctly identified with no false positives, demonstrating 100% sensitivity (95% confidence interval [CI], 91.2% to 100%) and 100% specificity (95% CI, 96.2% to 100%) for the assay. These findings provide a framework for an LC-MS/MS-based method for the direct detection of OXA-48 family carbapenemases from cultured isolates that may have utility in predicting carbapenem resistance and tracking hospital outbreaks of OXA-48-carrying organisms.

Analysis of a phase I pharmacokinetic (PK)/food effect study of AT-101 in patients with advanced solid tumors

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 2557-2557
Author(s):  
H. C. Pitot ◽  
D. Mould ◽  
J. Maleski ◽  
L. Leopold
Keyword(s):  
Phase 1 ◽  
Single Agent ◽  
Effect Study ◽  
Noncompartmental Analysis ◽  
Time Data ◽  
Phase 1 Study ◽  
Concentration Time ◽  
Effect Of Food ◽  
Ongoing Phase ◽  
High Calorie

2557 Background: AT-101 is an oral, pan-Bcl-2 inhibitor (Bcl-2, Bcl-XL, Bcl-W, Mcl-1). Overexpression of Bcl-2 family proteins is common in human cancers. AT-101 activity as a single agent as well as in combination with docetaxel has been reported. The ongoing Phase 1 study of AT-101 as a single agent was expanded to include a cohort of patients to determine the PK of AT-101 in fed and fasted states. Methods: Twelve patients (pts) were enrolled and randomized into cohorts of six pts each. Cohort A received AT-101 (80 mg) orally on day 1 on an empty stomach (fasted) and again on day 8 with a high fat high calorie breakfast (fed), per FDA guidelines. Cohort B received AT-101 on day 1 fed and on day 8 fasted. Preliminary plasma concentration time data for AT-101 from 10 patients administered 80 mg orally were evaluated using noncompartmental analysis. Log transformed peak concentration (Cmax) and exposure (AUC) were compared the between fed and fasted groups with the fasted group as the reference treatment. Results: Preliminary PK results from the first 10 pts are shown in the Table. For AUC and Cmax, the effect of food resulted in an approximately 42% and 5% increase, respectively. However the confidence intervals were not wholly outside the 80–125% intervals. Conclusions: These data indicate that food may increase AT-101 exposure in terms of AUC and Cmax. Updated results from all 12 pts will be presented at the meeting. Based on our preliminary results, it is recommended that AT-101 be taken at least an hour (or more) before or after food. [Table: see text] [Table: see text]

Quantification and pharmacokinetics of astragaloside II in rats by rapid liquid chromatography-tandem mass spectrometry

2014 ◽  
Vol 6 (17) ◽  
pp. 6815-6822 ◽  
Author(s):  
Haijun Qu ◽  
Meijuan Sun ◽  
Yu Cao ◽  
Longyuan Wang ◽  
Zhiwu Han
Keyword(s):  
Mass Spectrometry ◽  
Absolute Bioavailability ◽  
Tandem Mass ◽  
Time Profiles ◽  
Concentration Time ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass ◽  
Intravenous And Oral Administration ◽  
Poor Absorption

Mean plasma concentration–time profiles of AST II determined by the LC-MS/MS method after intravenous and oral administration of AST II to rats. The oral absolute bioavailability (F) of AST II in rats was calculated to be 0.79 ± 0.16%, suggesting its poor absorption and/or strong metabolism in vivo.

scholarly journals Efficacy of a Plasmodium vivax Malaria Vaccine Using ChAd63 and Modified Vaccinia Ankara Expressing Thrombospondin-Related Anonymous Protein as Assessed with Transgenic Plasmodium berghei Parasites

2013 ◽  
Vol 82 (3) ◽  
pp. 1277-1286 ◽  
Author(s):  
Karolis Bauza ◽  
Tomas Malinauskas ◽  
Claudia Pfander ◽  
Burcu Anar ◽  
E. Yvonne Jones ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Plasmodium Berghei ◽  
Malaria Vaccine ◽  
Protective Mechanisms ◽  
Content Type ◽  
Cell Responses ◽  
Malaria Vaccines ◽  
Modified Vaccinia Virus Ankara ◽  
Plasmodium Vivax Malaria ◽  
Antibody Titers

ABSTRACTPlasmodium vivaxis the world's most widely distributed malaria parasite and a potential cause of morbidity and mortality for approximately 2.85 billion people living mainly in Southeast Asia and Latin America. Despite this dramatic burden, very few vaccines have been assessed in humans. The clinically relevant vectors modified vaccinia virus Ankara (MVA) and the chimpanzee adenovirus ChAd63 are promising delivery systems for malaria vaccines due to their safety profiles and proven ability to induce protective immune responses againstPlasmodium falciparumthrombospondin-related anonymous protein (TRAP) in clinical trials. Here, we describe the development of new recombinant ChAd63 and MVA vectors expressingP. vivaxTRAP (PvTRAP) and show their ability to induce high antibody titers and T cell responses in mice. In addition, we report a novel way of assessing the efficacy of new candidate vaccines againstP. vivaxusing a fully infectious transgenicPlasmodium bergheiparasite expressingP. vivaxTRAP to allow studies of vaccine efficacy and protective mechanisms in rodents. Using this model, we found that both CD8+T cells and antibodies mediated protection against malaria using virus-vectored vaccines. Our data indicate that ChAd63 and MVA expressing PvTRAP are good preerythrocytic-stage vaccine candidates with potential for future clinical application.

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