Primaquine decreased plasma concentration of ritonavir: single- and repeated-dose study in Sprague Dawley rats

Abstract

Latar belakang: Penelitian ini dilakukan untuk meneliti pengaruh pemberian ritonavir dan primakuin bersamaan, yang diberikan dalam dosis tunggal atau dosis berulang pada konsentrasi plasma ritonavir pada tikus. Metode: Pada studi dengan pemberian dosis tunggal, 30 tikus Sprague Dawley jantan secara acak diberikan ritonavir 20 mg/kgBB atau ritonavir 20 mg/kgBB + primakuin 1,2 mg/kgBB atau ritonavir 20 mg/kgBB + ketokonazol 10 mg/kgBB. Ketokonazol digunakan sebagai kontrol positif penghambat metabolisme ritonavir. Pada studi dengan pemberian dosis berulang, 30 tikus Spraque Dawley secara acak diberikan ritonavir 20 mg/kgBB/hari atau ritonavir 20 mg/kgBB/hari + primaquine 1,2 mg/kgBB/hari atau ritonavir 20 mg/kgBB/hari + rifampisin 100 mg/kgBB/day. Rifampisin digunakan sebagai kontrol positif penginduksi metabolisme ritonavir. Hasil: Pada pemberian dosis tunggal, ketokonazol meningkatkan area dibawah kurva kadar plasma (AUC) ritonavir (↑114,8%, p< 0.05), sedangkan primakuin cenderung menurunkan AUC ritonavir (↓32,6%, p> 0.05). Pemberian dosis berulang menunjukkan bahwa rifampisin menurunkan AUC ritonavir (↓42,8%, p< 0.001), dan primakuin menurunkan AUC ritonavir (↓ 46,6%, p< 0.001).

Detection and quantification of Covid-19 antiviral drugs in biological fluids and tissues

“…LLE is a popular alternative to SPE in the bioanalytical field because it can be applied more quickly and easier, desalting samples very well and lessening the problem of source fouling in mass spectrometry analyses [ 87 ]. The solvents, useful to extract antiviral drugs from plasma, are ethyl acetate [ 43 , 88 ], diethyl ether [ 89 ] and methylene chloride [ 49 ], but the most widely employed remains methyltertbutyl ether (MTBE) [ 86 , 90 ] because it ensures better reproducibility and recovery [ 86 ]. MTBE was used for samples of urine and faeces as well [ 91 ].…”

“…Liquid chromatography coupled with UV-Vis detectors has been used in many works in order to quantify antiviral drugs in biological fluids, i.e. blood and plasma [ 43 , 73 , 89 , 90 , [114] , [115] , [116] , [117] , [118] , [119] ]. Currently, reversed-phase liquid chromatography is the method of first choice for this task.…”

“…The fastest run times of 4 and 5 minutes, respectively, occurred in isocratic methods for the determination of a single analyte, i.e. ritonavir and darunavir [ 89 , 90 ]. The longer run time for the determination of more than two drugs can be explained by the use of gradient elution mode in order to achieve good separation of drugs also from their own metabolites [ 123 ].…”