Research On Pharmacokinetics Of Albendazole Under Hypoxic Conditions

Objective To explore the pharmacokinetics of albendazole under hypoxic conditions and research the biological conversion of albendazole in liver microsomes in vitro for providing some references on clinical pharmaceutical research, clinical use of drugs, individual medication and avoiding adverse drug reactions of albendazole in plateau region. Methods 1. Albendazole orally administered to mice in the hypobaric chamber, eyeball blood were got at different time points. Normoxic group was given the same manner and taking blood. Drug concentrations in serum were detected by high performance liquid chromatography. Pharmacokinetics parameters of albendazole and its metabolites were calculated by DAS 2.0 software in each group. Chromatographic conditions: Agilent ZORBAX SB-C18 column(4.6 × 250 mm, 5μm), mobile phase: methanol- acetonitrile- sodium acetate solution( 0.1mmol·L-1, p H=5.0) using a gradient elution, flowing rate: 1ml·min-1, column temperature: 35℃, detection wavelength: 292 nm, injection volume: 30μl. 2. Mouse liver microsomes were extracted by differential centrifugation. After incubation system was optimized, biotransformation reaction of albendazole was started. Detection of albendazole conversion products was used by the same chromatographic condition to comparatively study the conversion characteristics of hypoxia and normoxia group microsomes. Results 1. Maximum surm concentrations of albendazole and albendazole sulfoxide in hypoxia group were(0.73 ± 0.05) and(4.40 ± 0.55) mg?L-1, respectively, the area under the curve were(54.35 ± 9.77) and(734.40 ± 26.55) mg?h?L-1. Normoxia group were:(0.23 ± 0.09),(8.55 ± 0.53) mg?L-1 and(28.48 ± 6.37),(922.36 ± 31.38) mg?h?L-1(n=10, P<0.01). 2. After biotransformations of albendazole in mouse liver microsomes were stoped, the highest concentration of albendazole sulfoxide in hypoxia group was(310.39 ± 32.63) μg?L-1, and(508.70 ± 41.45) μg?L-1 in normoxic group(n = 10, p <0.05). But albendazole sulfone had not been detected in conversion product. Conclusions 1. Metabolic rate of albendazole was slower under hypoxic conditions, and the yield of albendazole sulfoxide as active ingredient was less than normoxic conditions. 2. Albendazole transformation in microsomes is very slow in vitro. Albendazole sulfoxide conversion product is less than normoxia group and could not be transformed into albendazole sulfone. 3. Pharmacokinetics and liver microsome translational research showed that albendazole metabolized moderately under hypoxic conditions with a low yields of albendazole sulfoxide, in which the original drug residue was more than normoxic conditions. Therefore, the future conduct in plateau region when research on albendazole clinical use of drugs, pharmaceutical study and other work should be focused on increasing metabolic rate and reducing its remaining amount so that to avoid adverse drug reactions,but also to increase the capacity of albendazole sulfoxide in the future.