[Study of bioavailability of paclitaxel after sublingual administration]

The bioavailability of sublingual form of paclitaxel, developed in the pharmacology laboratory of pharmaceutical company - Legion "Provisus" is studied. Sublingual form of paclitaxel is an alcoholic solution of paclitaxel (1 mg/ml) with penetrator - dimethyl sulfoxide (DMSO) addition. Experiments were performed on 180 white mongrel male mice each of 25-30 g. The animals were divided into three groups. The first group served for control. 10 mg/kg of taxol was injected (once) in the lateral tail vein of the first group animals. A solution was prepared by diluting taxol with physiological sodium chloride solution until to a final concentration of paclitaxel to 1 mg/ml. The dose of 10 mg/kg (single dose) was applied under the tongue of the second group animals. Paclitaxel (substance) was extracted with dichloromethane - Taxol (by liquid-liquid extraction) for the manufacturing of a sublingual form. Unlike the second group, the third group animals took the same dose of sublingual form of paclitaxel orally (by gavage). The concentration of paclitaxel in plasma was studied by reversed-phase HPLC with spectrophotometric detection at λ = 227 nm by Woo JS et al. (2003) method. Bioavailability was determined by comparing the concentration of paclitaxel in blood after sublingual and intravenous use of Taxol (as an area under the curve of concentration versus time). It is established that the bioavailability of sublingual forms of paclitaxel was 42.4%, Cmax = 615 ± 73 ng × ml(-1) and tmax = 30-35 min. The value of the initial volume of distribution of paclitaxel (Vd = 3,14 ± 0,85 l × kg(-1)) also shows its intensive penetration to the organs and tissues. The half-life of the drug on the terminal segment of concentration-time curve was averaged 1,06 ± 0,21 h. The results create the preconditions for further preclinical study of sublingual form of paclitaxel, as the bioavailability of paclitaxel after sublingual application allows to have a systemic effect on the tumor process.