TITLE:
Pharmacokinetic Study and Toxicity of Leukovir: A New Combined Drug for the Treatment of Multiple Sclerosis
AUTHORS:
Elena N. Kalinichenko, Irina V. Ponteleeva, Marina B. Golubeva
KEYWORDS:
Leukovir, Cladribine, Ribavirin, Multiple Sclerosis, Pharmacokinetics, Toxicity
JOURNAL NAME:
Advances in Biological Chemistry,
Vol.12 No.1,
January
21,
2022
ABSTRACT: Leukovir, an enteric-coated tablet, is the original drug product for
internal use. The well-known nucleosides cladribine and ribavirin are the
active ingredients of the drug product leukovir. Pharmacokinetic parameters of
the drug product for the internal use of leukovir active ingredients have been
established. The cladribine half-absorption period was t1/2a = 49.5 h, C0 = 276.4 μg/ml, Cmax = 6.0 μg/ml.
Distribution and accumulation parameters (Vd, Vss and AUC) have
indicated that the drug distribution between the blood cells and blood plasma
takes place in the same way, irrespective of the dosage form. Cladribine
half-life period is t1/2e = 0.62 hours. The molecule total
clearance and average lifetime in the body in the case of subcutaneous drug
administration are approximately the same. Ribavirin is characterized by a
half-absorption period of t1/2a = 0.71 h, C0 = 115.6 μg/ml and Cmax = 75.5 μg/ml. Ribavirin total volume of distribution (Vd = 1.3 l/kg) and stationary volume of distribution (Vss = 1.64 l/kg) were
practically similar to leukovir when administered subcutaneously. The AUC value
= 504.2 μg h/ml, which is 2.5 times less than that in the case of drug form
administration. Leukovir was regarded as slightly toxic in an acute toxicity
study. The risk of cumulation for this drug product is low.