Dataset Information

Determination of piperaquine concentration in human plasma and the correlation of capillary versus venous plasma concentrations.

ABSTRACT: Background: A considerable challenge in quantification of the antimalarial piperaquine in plasma is carryover of analyte signal between assays. Current intensive pharmacokinetic studies often rely on the merging of venous and capillary sampling. Drug levels in capillary plasma may be different from those in venous plasma, Thus, correlation between capillary and venous drug levels needs to be established.

Methods: Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was used to develop the method. Piperaquine was measured in 205 pairs of capillary and venous plasma samples collected simultaneously at ?24hr post dose in children, pregnant women and non-pregnant women receiving dihydroartemisinin-piperaquine as malaria chemoprevention. Standard three-dose regimen over three days applied to all participants with three 40mg dihydroartemisinin/320mg PQ tablets per dose for adults and weight-based dose for children. Correlation analysis was performed using the program Stata® SE12.1. Linear regression models were built using concentrations or logarithm transformed concentrations and the final models were selected based on maximal coefficient of determination (R2) and visual check.

Results: An LC-MS/MS method was developed and validated, utilizing methanol as a protein precipitation agent, a Gemini C18 column (50x2.0mm, 5?m) eluted with basic mobile phase solvents (ammonium hydroxide as the additive), and ESI+ as the ion source. This method had a calibration range of 10-1000 ng/mL and carryover was negligible. Correlation analysis revealed a linear relationship: Ccap = 1.04×Cven+4.20 (R2 = 0.832) without transformation of data, and lnCcap = 1.01×lnCven+0.0125, (R2 = 0.945) with natural logarithm transformation. The mean ratio (±SD) of Ccap/Cven was 1.13±0.42, and median (IQR) was 1.08 (0.917, 1.33).

Conclusions: Capillary and venous plasma PQ measures are nearly identical overall, but not readily exchangeable due to large variation. Further correlation study accounting for disposition phases may be necessary.

SUBMITTER: Mwebaza N

PROVIDER: S-EPMC7259774 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Determination of piperaquine concentration in human plasma and the correlation of capillary versus venous plasma concentrations.

Mwebaza Norah N Cheah Vincent V Forsman Camilla C Kajubi Richard R Marzan Florence F Wallender Erika E Dorsey Grant G Rosenthal Philip J PJ Aweeka Francesca F Huang Liusheng L

PloS one 20200529 5

<h4>Background</h4>A considerable challenge in quantification of the antimalarial piperaquine in plasma is carryover of analyte signal between assays. Current intensive pharmacokinetic studies often rely on the merging of venous and capillary sampling. Drug levels in capillary plasma may be different from those in venous plasma, Thus, correlation between capillary and venous drug levels needs to be established.<h4>Methods</h4>Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) ...[more]

PMID: 32470030

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Project description:One promising new Artemisinin-based combination therapies (ACTs) is dihydroartemisinin-piperaquine (DHA-PQ). However, the pharmacokinetics of piperaquine and the relationship between drug levels and clinical efficacy are incompletely characterized, particularly in children.We performed a single-arm open-label trial in Bobo-Dioulasso, Burkina Faso. A total of 379 participants aged 6 months or more with uncomplicated falciparum malaria were enrolled. Each participant received daily dose of DHA-PQ for three days and followed for 42 days. Parasitological efficacy was analyzed, considering rates of recrudescence and overall recurrence. PK was an exploratory endpoint and a priori, no sample size had been determined. Day 7 capillary and venous plasma concentrations of piperaquine were measured in children aged 2-10 years.Of the 379 participants, 365 (96.3%) completed 42 days of follow-up. The median daily dose of PQ was 18.5 mg/kg [6.5-24]. Treatment with DHA-PQ was well tolerated with fever and parasitemia resolution within 48 hours in nearly all children. Recurrent malaria within 42 days of follow-up occurred in 31.3% (10/34) of children less than 2 years old, 16.0% (16/106) of those aged 2-5 years, 9.4% (15/160) of those aged 5-10 years, and none (0/68) of those over 10 years old. After genotyping, 3 of 41 recurrent episodes were recrudescence. An exploratory analysis shows that children with successful treatment outcomes had significantly higher median plasma concentrations of PQ compared to those with recurrent malaria within 42 days after therapy, considering either capillary samples (68 ng/ml [50-85] compared to 48 ng/ml [36-55], p<0.001) or venous samples (42 ng/ml [29-59] compared to 25 ng/ml [19-44], p<0.001).DHA-PQ was effective for uncomplicated P. falciparum malaria treatment and offers an alternative to other ACTs. Recurrent malaria was mainly due to new infections after treatment and was correlated with low day 7 PQ concentration in the youngest patients.Controlled-Trials.com ISRCTN59761234.

Project description:BackgroundGuidelines for the emergency management of mild traumatic brain injury have been used for over a decade and are considered safe. However, they recommend computerized tomography for at least half of these patients. The Scandinavian Neurotrauma Committee guideline uses serum S100B protein level to rule out intracranial hemorrhage. Analysis of capillary serum S100B protein level has not yet been employed for this purpose. The primary aim of this study was to investigate the correlation and agreement of capillary and venous serum S100B protein level over a spectrum of concentrations typical for mild traumatic brain injury.MethodsEighteen patients with traumatic intracranial hemorrhage and 39 volunteers without trauma to the head within the past 7 days were recruited. Blood was sampled from patients with intracranial hemorrhage daily up to four consecutive days and healthy volunteers were sampled once during the study. One venous and two capillary samples were drawn at each sampling event. Samples were analyzed using the Cobas e411 S100 electrochemiluminescence assay.ResultsMedian serum S100B protein level of capillary sampling 1 was 0.12 (IQR 0.075-0.21) μg/l and median serum S100B protein level of capillary sampling 2 was 0.13 (IQR 0.08-0.22) μg/l. Median serum S100B protein level of all venous samples was 0.05 (IQR 0.03-0.07) μg/l. Correlation plots of capillary and venous samples showed poor correlation and Bland-Altman plots showed a large dispersion of samples and wide limits of agreement.ConclusionThe results of this study indicate that correlation and agreement between capillary and venous samples are low, and because of this, we cannot recommend studies on capillary serum S100B protein level to rule out intracranial hemorrhage in mild traumatic brain injury. Given the limitations of the current sampling and analysis methods of capillary protein S100B protein level, we conclude that evaluating its predictive ability to rule out intracranial hemorrhage should be withheld until more reliable methods can be incorporated into the study design.

Dataset Information

Determination of piperaquine concentration in human plasma and the correlation of capillary versus venous plasma concentrations.

Publications

Determination of piperaquine concentration in human plasma and the correlation of capillary versus venous plasma concentrations.

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