| Autor: |
Probst A; Swiss Tropical and Public Health Institute, Allschwil, Switzerland.; University of Basel, Basel, Switzerland., Hofmann D; Swiss Tropical and Public Health Institute, Allschwil, Switzerland.; University of Basel, Basel, Switzerland., Fedorova OS; Siberian State Medical Universitygrid.412593.8, Tomsk, Russia., Mazeina SV; Siberian State Medical Universitygrid.412593.8, Tomsk, Russia., Sokolova TS; Siberian State Medical Universitygrid.412593.8, Tomsk, Russia., Golovach E; Siberian State Medical Universitygrid.412593.8, Tomsk, Russia., Keiser J; Swiss Tropical and Public Health Institute, Allschwil, Switzerland.; University of Basel, Basel, Switzerland. |
| Jazyk: |
angličtina |
| Zdroj: |
Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2022 Oct 18; Vol. 66 (10), pp. e0052622. Date of Electronic Publication: 2022 Sep 12. |
| DOI: |
10.1128/aac.00526-22 |
| Abstrakt: |
Opisthorchiasis due to the liver fluke Opisthorchis felineus is highly prevalent in rural regions of Western Siberia, causing severe liver and bile duct maladies. Praziquantel administered as a three-dose regimen is the only drug used to treat O. felineus-infected individuals. A simpler single-dose treatment might serve as an alternative. The aim of this study was to compare the pharmacokinetic (PK) properties of single, ascending doses of praziquantel compared to multiple dosing in patients infected with O. felineus to contribute to updated treatment guidelines. Dried blood spots (DBSs) of 110 adults were collected at 11 time points post-drug administration at single oral doses of 20, 40, and 60 mg/kg, as well as 3× 20 mg/kg (4 h dosing interval). DBS samples were analyzed using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, and PK parameters were obtained for R -, S -, and R-trans -4-OH-praziquantel employing noncompartmental analysis. We observed the highest drug exposure for all analytes when the triple-dose scheme was used; area under the concentration-time curve from 0 to 24 h (AUC 0-24 ) values of 8.04, 27.75, and 36.38 μg/mL·h were obtained, respectively. Maximal plasma concentrations ( C max ) values of 1.72, 4.89, and 2.69 μg/mL were calculated for R -, S -, and R-trans -4-OH-praziquantel, respectively, when patients were given a single 60-mg/kg dose, and they peaked at 1.5 and 2 h for the enantiomers and at 3 h for the metabolite. The herein-generated PK data, together with results that will be obtained from the integrated efficacy study, lay the groundwork for a possibly optimized treatment scheme for O. felineus-infected patients. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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