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 × 10
cells/mm
, with an absolute neutrophil count (ANC) of 0 × 10
cells/mm
) 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 × 10
cells/mm
. 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.
•We developed a HPLC-MS method for analysis of therapeutic agents for LF treatment.•The method was validated as per ICH and FDA guidelines.•The method was successfully applied to pharmacokinetic and ...biodistribution studies.
A sensitive and relatively fast, cost-effective high-performance liquid chromatographic method coupled with mass spectrometer (HPLC-MS) is herein reported for the first time for a simultaneous quantification of plasma and organs concentration of three therapeutic agents that are widely used in treatment of lymphatic filariasis (LF), namely, doxycycline (DOX), diethylcarbamazine (DEC) and albendazole (ABZ) metabolites. The method was developed and validated as per ICH and FDA guidelines and successfully employed to quantify DOX, DEC and ABZ metabolites (albendazole sulfoxide (ABZ-OX) and albendazole sulfone (ABZ-ON)) in the plasma and organs of Sprague Dawley rats after oral concomitant administration of the above mentioned therapeutic agents. Importantly, a simple, one-step protein precipitation and extraction method was used to extract the four compounds efficiently with a recovery in the range of 79.88 ± 5.02%–90.71 ± 5.13%, 85.72 ± 7.22%–93.17 ± 5.55%, 94.38 ± 7.35%–101.00 ± 8.88% and 94.38 ± 7.35%–99.87 ± 10.22% in plasma and organs for DOX, DEC, ABZ-OZ and ABZ-ON, respectively. Separation of all analytes was performed on a Xselect CSH™ C18 HPLC column (Waters, 3.0 x 150 mm, 3.5 μm particle size) with gradient elution employing a mobile phase consisting of 0.1% v/v formic acid in water and methanol with a run time of 20 min. Quantification was carried out employing a single, quadruple MS detector operated with single ion monitoring (SIM) mode and the ion transitions at m/z of 445.4, 200.2, 282.3 and 298.3 for DOX, DEC, ABZ-OX and ABZ-ON respectively. The MS response for plasma samples was linear across the concentration range of 2.5–2500 ng/mL for DOX, 0.5–500 ng/mL for DEC, 1–1000 ng/mL for ABZ-OX and ABZ-ON with a correlation coefficient (r2) ≥ 0.998. The method was selective, precise and accurate. This method allowed us to get an insight into the pharmacokinetics and biodistribution of the three therapeutic agents after simultaneous oral administration to Sprague Dawley rats. This bioanalytical method could provide a reliable, reproducible and excellent tool for routine therapeutic drug monitoring of the above mentioned therapeutic agents and also support other clinical pharmacokinetic-based studies.
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Intranasal Microemulsions (MEs) for nose to brain delivery of a novel combination of Albendazole sulfoxide (ABZ-SO) and Curcumin (CUR) for Neurocysticercosis (NCC), a brain infection ...are reported. MEs prepared by simple solution exhibited a globule size <20nm, negative zeta potential and good stability. The docosahexaenoic acid (DHA) ME revealed high and rapid ex vivo permeation of drugs through sheep nasal mucosa. Intranasal DHA ME resulted in high brain concentrations and 10.76 (ABZ-SO) and 3.24 (CUR) fold enhancement in brain area-under-the-curve (AUC) compared to intravenous DHA MEs at the same dose. Direct nose to brain transport (DTP) of >95% was seen for both drugs. High drug targeting efficiency (DTE) to the brain compared to Capmul ME and drug solution (P<0.05) suggested the role of DHA in aiding nose to brain delivery. Histopathology study confirmed no significant changes. High efficacy of ABZ-SO: CUR (100:10ng/mL) DHA ME in vitro on Taenia solium cysts was confirmed by complete ALP inhibition and disintegration of cysts at 96h. Considering that the brain concentration at 24h was 1400±160.1ng/g (ABZ-SO) and 120±35.2ng/g (CUR), the in vitro efficacy seen at a 10 fold lower concentration of the drugs strongly supports the assumption of clinical efficacy. The intranasal DHA ME is a promising delivery system for targeted nose to brain delivery.
Background. Available treatments for lymphatic filariasis (LF) are limited in their longterm clearance of microfilaria from the blood. The safety and efficacy of a single-dose triple-drug therapy of ...the antifilarial drugs diethylcarbamazine (DEC), ivermectin (IVM), and albendazole (ALB) for LF are unknown. Methods. We performed a pilot study to test the efficacy, safety, and pharmacokinetics of single-dose DEC, IVM, and ALB in Wuchereria bancrofti-infected Papua New Guineans. Adults were randomized into 2 treatment arms, DEC 6 mg/kg + ALB 400 mg (N = 12) or DEC 6 mg/kg + ALB 400 mg + IVM 200 μg/kg (N = 12), and monitored for microfilaria, parasite antigenemia, adverse events (AEs), and serum drug levels. Results. Triple-drug therapy induced >2-log reductions in microfilaria levels at 36 and 168 hours after treatment compared with approximately 1-log reduction with 2 drugs. All 12 individuals who received 3 drugs were microfilaria negative 1 year after treatment, whereas 11 of 12 individuals in the 2-drug regimen were microfilaria positive. In 6 participants followed 2 years after treatment, those who received 3 drugs remained microfilaria negative. AEs, particularly fever, myalgias, pruritus, and proteinuria/hematuria, occurred in 83% vs 50% of those receiving triple-drug compared to 2-drug treatment respectively (P = .021); all resolved within 7 days after treatment. No serious AEs were observed in either group. There was no significant effect of IVM on DEC or ALB drug levels. Conclusions. Triple-drug therapy is safe and more effective than DEC + ALB for Bancroftian filariasis and has the potential to accelerate elimination of lymphatic filariasis. Clinical Trials Registration. NCT01975441.
•Sample preparation was accomplished by protein precipitation with methanol.•Only 3.5min was needed for an analytical run.•This method was successfully applied to the pharmacokinetic studies of ...albendazole sufoxide.
A rapid, simple and sensitive method was developed and validated using liquid chromatography–tandem mass spectrometry (LC–MS/MS) for determination of albendazole sulfoxide (ABZOX) in human plasma. The plasma samples were extracted by protein precipitation using albendazole sulfoxide-d3 as internal standard (IS). The chromatographic separation was performed on Waters Xbridge C18Column (100×4.6mm, 3.5μm) with a mobile phase consisting of ammonia solution, water and methanol at a flow rate of 0.70mL/min. ABZOX was detected and identified by mass spectrometry with electrospray ionization (ESI) in positive ion and multiple-reaction monitoring (MRM) mode. The method was linear in the range of 3–1500ng/mL for ABZOX. This method was successfully applied to the bioequivalence study in human plasma samples.
Albendazole is an effective anthelmintic intensively used for decades. However, profound pharmacokinetic (PK) characterization is missing in children, the population mostly affected by helminth ...infections. Blood microsampling would facilitate PK studies in pediatric populations but has not been applied to quantify albendazole's disposition. Quantification methods were developed and validated using liquid chromatography-tandem mass spectrometry to analyze albendazole and its metabolites albendazole sulfoxide and albendazole sulfone in wet samples (plasma and blood) and blood microsamples (dried-blood spots DBS; Mitra). The use of DBS was limited by a matrix effect and poor recovery, but the extraction efficiency was constant throughout the concentration range. Hookworm-infected adolescents were venous and capillary blood sampled posttreatment with 400 mg albendazole and 25 mg/kg oxantel pamoate. Similar half-life (
= ∼1.5 h), time to reach the maximum concentration (
= ∼2 h), and maximum concentration (
= 12.5 to 26.5 ng/ml) of albendazole were observed in the four matrices. The metabolites reached
after ∼4 h with a
of ca. 7 to 8 h. A statistically significant difference in albendazole sulfone's
as determined by using DBS and wet samples was detected.
of albendazole sulfoxide (288 to 380 ng/ml) did not differ among the matrices, but higher
of albendazole sulfone were obtained in the two microsampling devices (22 ng/ml) versus the wet matrices (14 ng/ml). In conclusion, time-concentration profiles and PK results of the four matrices were similar, and the direct comparison of the two microsampling devices indicates that Mitra extraction was more robust during validation and can be recommended for future albendazole PK studies.
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•Trace albendazole sulfoxide concentration in the biological samples was detected.•Response surface methodology based on central composite design was used.•The proposed method had the ...advantage of using a small sample volume.•The method was simple, rapid, sensitive, eco-friendly, and reliable.
In this research study, a method of dispersive-micro-solid phase extraction (D-µ-SPE) combined with molecularly imprinted polymer nanoparticles (MIP-NPs) with HPLC-UV was developed for the fast and selective detection of the trace amount of albendazole sulfoxide (ABZSO) in the biological samples. To investigate the effective factors on ABZSO microextraction by the method, central composite design (CCD) was utilized, and the optimum conditions for ABZSO microextraction were sample pH of 8.0, MIP-mass of 15 mg, sonication time of 12 min, and eluent (methanol) volume of 0.25 mL. Under the obtained optimal extraction conditions, the value for the limit of detection (LOD) and limit of quantification (LOQ) was respectively showed to be 0.074 and 0.246 ng mL−1. In addition, the calculated peak areas exhibited a linear relationship with the ABZSO concentration ranging from 0.4 to 4200 ng mL−1. The analyses of the samples including human plasma and urine, and water were successfully performed by the usage of the D-µ-SPE method, which was a simple and sensitive technique and a suitable alternative for the analysis of ABZSO. In the analysis of ABZSO in various samples, the recoveries at various levels of ABZSO concentrations (50, 300, and 500 ng mL−1) were in the range of 95.7–103.0 %, and the relative standard deviations (RSDs; n = 3) varied from 2.2 to 4.4%.
Albendazole (ABZ) is the primary treatment for alveolar echinococcosis (AE); however, its limited solubility impacts oral bioavailability, affecting therapeutic outcomes. In this study, various ...ABZ-solubilizing formulations, including albendazole crystal dispersion system (ABZ-CSD), albendazole hydrochloride-hydroxypropyl methylcellulose phthalate composite (T
), and albendazole hydroxyethyl sulfonate-hydroxypropyl methylcellulose phthalate composite (T
), were developed and evaluated. Physicochemical properties as well as liver enzyme activity were analyzed and their pharmacodynamics in an anti-secondary hepatic alveolar echinococcosis (HAE) rat model were investigated. The formulations demonstrated improved solubility, exhibiting enhanced inhibitory effects on microcysts in HAE model rats compared to albendazole tablets. However, altered hepatic drug-metabolizing enzymes in HAE model rats led to increased ABZ levels and reduced ABZ-SO production, potentially elevating drug toxicity. These findings emphasize the importance of dose adjustments in patient administration, considering the impact of alveolar echinococcosis on rat hepatic drug metabolism.
Helminthiasis remains a public health issue in endemic areas. Various drugs have been proposed to improve efficacy against helminths. The study aimed to assess the safety and efficacy of three ...different anthelmintic combinations to treat
infections. We conducted a randomized assessors-blind clinical trial involving children aged 2-17 years with
. Participants were randomly assigned to one of three treatment arms. On the first and third days, all participants got albendazole 400 mg, and on the second day, albendazole (arm A), mebendazole 500 mg (arm B), or pyrantel 125 mg/kg (arm C). We assessed treatment efficacy using the cure rate (CR) and egg reduction rate (ERR) at 3 and 6 weeks post-treatment. At 3 weeks post-treatment, ERR and CR were highest in study arm A ERR = 94%, 95% confidence interval (CI): 92-95; CR = 71%; 95% CI: 58-81 compared to the B and C arms. Decrease in ERR was significant only for arm B versus arm A (
-value <0.001); decrease in ERR was significant for arms B and C (
-value <0.001). No statistical difference was observed in CR when comparing arms A and B (
-value =1.00) and C (
-value =0.27). At 6 weeks, a decrease in ERR was observed in three arms, significant only for arm C, 81% (95% CI: 78-83). A significant increase in egg counts was observed between 3 and 6 weeks post-treatment. All treatments were safe with mild adverse events. Albendazole 400 mg/day (arm A) showed the highest efficacy against trichuriasis. Nonetheless, this treatment regimen was able to cure half of the treated individuals highlighting concerns about controlling the transmission of
.CLINICAL TRIALRegistered at ClinicalTrials.gov (NCT04326868).
•Albendazole and its metabolites were monitored using an UPLC-Q-TOF-MS method.•Method complied related validation guidelines of US-FDA and CFDA.•PK and tissue distribution study of liposomal ...albendazole were performed.•Emulsion albendazole was used as reference preparation.•The experimental animals were naturally echinococcus granulosus infected sheep.
Albendazole (ABZ) is the first-line drug in treating echinococcosis, which is recommended by WHO. To address the poor bioavailability of albendazole, liposomal albendazole was formulated and is available in our hospital for many years. In this study, a sensitive, reliable and accurate UPLC-Q-TOF-MS method was developed and validated for the determination of albendazole and its metabolites, albendazole sulfoxide (ABZSO), albendazole sulfone (ABZSO2) and albendazole-2-aminosulfone (ABZSO2NH2) in naturally echinococcus granulosus (E. granulosus) infected sheep plasma and tissues with mebendazole (MBZ) as the internal standard (IS). Plasma and tissues samples were prepared by protein precipitation method. The separation was performed on an ACQUITY UPLC® BEH C18 column (2.1 × 50 mm, 1.7 μm) with a gradient mobile phase consisting of methanol and water containing 0.1% formic acid at 0.4 mL/min. The detection was performed on a quadrupole time-of-flight (Q-TOF) high-resolution mass spectrometer using positive electrospray ionization (ESI) source with a chromatographic run time of 6.0 min. The detection was operated using target ions of M + H+ at m/z 266.096 for ABZ, m/z 282.091 for ABZSO, m/z 298.086 for ABZSO2, m/z 240.081 for ABZSO2NH2 and m/z 296.104 for IS in selective ion mode, respectively. This method was validated in terms of selectivity, linearity, precision, accuracy, recovery, matrix effect, dilution effect, carryover effects, stability, calibration curve and LLOQ. All validation parameter results were within the acceptable range described in guideline for bioanalytical method validation. This method has been successfully applied to the pharmacokinetic study following single and multiple oral dose of 10 mg/kg liposomal albendazole, and tissue distribution study following multiple oral dose of 10 mg/kg, with emulsion albendazole as the reference preparation. The results in the article will provide valuable information for use in clinical applications of liposomal albendazole and also be beneficial for further development of liposomal albendazole in future studies.
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