Case Report: Analytically Confirmed Severe Albenzadole Overdose Presenting with Alopecia and Pancytopenia.

Internet-facilitated self-diagnosis and treatment is becoming more prevalent, putting individuals at risk of toxicity when drugs are acquired without medical oversight. We report a patient with delusional parasitosis who consumed veterinary albendazole purchased on the Internet, leading to pancytopenia, transaminase elevation, and alopecia. A 53-year-old man was sent to the emergency department (ED) by his gastroenterologist because of abnormal laboratory results. The patient had chronic abdominal pain and believed he was infected with parasites. He purchased two bottles of veterinary-grade albendazole on the Internet, and over the 3 weeks before his ED visit, he consumed 113.6 g of albendazole (a normal maximal daily dose is 800 mg). Five days before admission, he noticed hair loss and a rash on his face. His examination was notable for significant scalp hair loss and hyperpigmentation along the jaw line. Laboratory studies were remarkable for pancytopenia (most notably a white blood cell count (WBC) of 0.4 × 103 cells/mm3, with an absolute neutrophil count (ANC) of 0 × 103 cells/mm3) and transaminase elevation (aspartate aminotransferase [AST] 268 IU/L, alanine aminotransferase [ALT] 89 IU/L). He developed a fever and was treated with antibiotics and colony-stimulating factors for presumed neutropenic bacteremia. Over the course of 1 week, his hepatic function normalized and his ANC increased to 3,000 × 103 cells/mm3. Serial albendazole and albendazole sulfoxide concentrations were measured in serum and urine by liquid chromatography-quadruple time-of-flight mass spectrometry. On day 2, his serum concentrations were 20.7 ng/mL and 4,257.7 ng/mL for albendazole and albendazole sulfoxide, respectively. A typical peak therapeutic concentration for albendazole sulfoxide occuring at 2-5 hours post-ingestion is 220-1,580 ng/mL. Known adverse effects of albendazole include alopecia, transaminase elevation, and neutropenia. Pancytopenia leading to death from septic shock is reported. In our patient, prolonged use of high-dose albendazole resulted in a significant body burden of albendazole and albendazole sulfoxide, leading to pancytopenia, transaminase elevation, and alopecia. He recovered with supportive therapy.

Study on the interaction between albendazole and eosin Y by fluorescence, resonance Rayleigh scattering and frequency doubling scattering spectra and their analytical applications.

In pH 3.25-3.35 Britton-Robinson (BR) buffer solution, albendazole (ABZ) could react with eosin Y (EY) to form a 1:1 ion-association complex, which not only results in the quenching of fluorescence, but also resulted in the great enhancement of resonance Rayleigh scattering (RRS) and frequency doubling scattering (FDS). Furthermore, a new RRS spectrum will appear, and the maximum RRS wavelength was located at about 356nm. The detection limit for ABZ were 21.51ng mL(-)(1) for the fluorophotometry, 6.93ng mL(-)(1) for the RRS method and 12.89ng mL(-)(1) for the FDS method. Among them, the RRS method had the highest sensitivity. The experimental conditions were optimized and effects of coexisting substances were evaluated. Meanwhile, the influences of coexisting substances were tested. The methods have been successfully applied to the determination of ABZ in capsules and human urine samples. The composition and structure of the ion-association complex and the reaction mechanism were discussed.

Enantioselective renal excretion of albendazole metabolites in patients with neurocysticercosis.

The present study investigates the urinary excretion of the enantiomers of (+)- and (-)-albendazole sulfoxide (ASOX) and albendazole sulfone (ASON) in 12 patients with neurocysticercosis treated with albendazole for 8 days (7.5 mg/kg/12 h). Serial blood samples (0-12 h) and urine (three periods of 8 h) were collected after administration of the last dose of albendazole. Plasma and urine (+)-ASOX, (-)-ASOX, and ASON metabolites were determined by HPLC using a chiral phase column (Chiralpak AD) with fluorescence detection. The pharmacokinetic parameters (P < 0.05) for (+)-ASOX, (-)-ASOX, and ASON metabolites are reported as means (95% CI); amount excreted (Ae) = 3.19 (1.53-4.85) vs. 0.72 (0.41-1.04) vs. 0.08 (0.03-0.13) mg; plasma concentration-time area under the curve, AUC(0-24) = 3.56 (0.93-6.18) vs. 0.60 (0.12-1.08) vs. 0.38 (0.20-0.55) microg x h/ml, and renal clearance Cl(R) = 1.20 (0.66-1.73) vs. 2.72 (0.39-5.05) vs. 0.25 (0.13-0.37) l/h. Sulfone formation capacity, expressed as the Ae ratio ASON/ASOX + ASON, was 2.21 (1.43-2.99). These data point to enantioselectivity in the renal excretion of ASOX as a complementary mechanism to the metabolism responsible for the plasma accumulation of (+)-ASOX. The results also suggest that the metabolite ASON is partially eliminated as a reaction product of the subsequent metabolism.

Sex differences in the disposition of albendazole metabolites in sheep.

Sex differences in the disposition of albendazole metabolites in sheep after oral administration of 20 mg/kg of netobimin have been studied. Some kinetic parameters of both metabolites show statistical differences between sexes; the sulphoxide and sulphone t1/2beta and MRT were lower in male animals than in females. Peak concentrations and AUC of sulphone metabolites were higher in males suggesting a greater oxidation rate compared with females. Urine excretion of albendazole metabolites, sulphoxide, sulphone, and amino sulphone appeared to be greater in female sheep than in males, mainly the sulphoxide metabolite. These differences between sexes can be caused by male sexual hormones, because testosterone and progesterone can induce or inhibit the microsomal Cytochrome P450 metabolism. Plasma protein-binding of albendazole sulphoxide and albendazole sulphone has been studied between male and female sheep, also their binding to sheep albumin and globulins. Both albendazole metabolites readily bind to sheep albumin and globulins. Male animals show a significantly lower binding of albendazole metabolites than females. These differences could be responsible for the non-esterified fatty acids (NEFA) present in the plasma. Males have significantly higher plasma levels of NEFA than females and which may compete with albumin for binding to albendazole metabolites.

Direct separation of albendazole sulfoxide enantiomers by liquid chromatography on a chiral column deriving from (S)-N-(3,5-dinitrobenzoyl) tyrosine: application to enantiomeric assays on plasma samples.

The direct enantiomeric resolution of albendazole sulfoxide (SOABZ), an anthelmintic drug belonging to the benzimidazole class, is reported on a chiral stationary phase (CSP) synthesized by covalent binding of (S)-N-(3,5-dinitrobenzoyl)tyrosine-O-(2-propen-1-yl) methyl ester on a gamma-mercaptopropyl-silanized silica gel. A comparison with the resolution achieved on commercially available Pirkle-type CSPs obtained from N-(3,5-dinitrobenzoyl) derivatives of (R)-phenyglycine or (S)-phenylalanine is described. Some structurally related chiral sulfoxides including oxfendazole (SOFBZ) are also studied. Optimization of the mobile phase nature and composition is investigated showing that a hexane-dioxane-ethanol ternary mixture affords an almost baseline resolution (Rs = 1.25); however, in this case, albendazole sulfone (SO2ABZ) is eluted between the two sulfoxide enantiomers; accordingly, a hexane-ethanol mobile phase would be preferred for biological samples containing both metabolites. The influence of temperature on the resolution is depicted with a hexane-ethanol mobile phase. Finally, application to the enantiomeric assays of SOABZ in plasmatic extracts of rat, sheep, bovin, and man after oral administration of albendazole (sulfoxidized to SOABZ and SO2ABZ) is reported. Some distortions in the enantiomeric ratios are evidenced depending on the species.