Optimal single sampling time-point for monitoring of praziquantel exposure in children

Sci Rep. 2021 Sep 9;11(1):17955. doi: 10.1038/s41598-021-97409-x.

Abstract

Praziquantel pharmacokinetics studies in schistosomiasis infected children are scarce partly due to the challenges/complexity of intensive blood sampling in the target population. This study was aimed to investigate the optimal single sampling time-point for monitoring praziquantel exposure. This was intensive pharmacokinetic study conducted among 32 Schistosoma mansoni infected children treated with an oral standard single-dose 40 mg/kg praziquantel. Plasma samples were collected at 0, 1, 2, 4, 6 and 8 h post-praziquantel administration. Quantification of praziquantel and its enantiomers (R- and S-praziquantel) concentrations was done by Liquid chromatography-tandem mass spectrometer (LC-MS/MS). The correlation between area under the plasma concentration-time curve from 0 to 8 h (AUC8) and plasma concentrations at each specific sampling time-point was determined by Pearson's correlation coefficient (r2). The median age (range) of the study population was 12.5 years (10-17). The study participants were 17 males and 15 females. Both total praziquantel and its enantiomers (R- and S-praziquantel) displayed a wide inter-individual pharmacokinetic variability. Regression analysis indicated that, plasma concentrations collected at 4 h post-dose had a significantly highest correlation with the AUC8 for both total praziquantel (r2 = 0.81, p < 0.001) and S-praziquantel (r2 = 0.84, p < 0.001) than any other sampling time-point; while for R-praziquantel, plasma concentrations collected at 6 h sampling time-point had a significantly highest correlation with the AUC8 (r2 = 0.79, p < 0.001) than any other sampling time-point. Four hours sampling time-point post-praziquantel administration is ideal optimal single sampling time-point for therapeutic monitoring of total praziquantel exposure while 6 h sampling time-point is suitable for monitoring of a pharmacologically active R-praziquantel enantiomer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Animals
  • Anthelmintics / administration & dosage*
  • Anthelmintics / blood
  • Anthelmintics / pharmacokinetics*
  • Biological Availability
  • Blood Specimen Collection / methods
  • Child
  • Chromatography, Liquid
  • Drug Monitoring / methods*
  • Feces / parasitology
  • Female
  • Humans
  • Isomerism
  • Male
  • Praziquantel / administration & dosage*
  • Praziquantel / blood
  • Praziquantel / pharmacokinetics*
  • Schistosoma mansoni / isolation & purification*
  • Schistosomiasis mansoni / blood
  • Schistosomiasis mansoni / drug therapy*
  • Schistosomiasis mansoni / parasitology
  • Tandem Mass Spectrometry

Substances

  • Anthelmintics
  • Praziquantel