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Veterinary Journal (London, England :... May 2003Three single oral doses (8.5, 10, and 14 mg/kg) of a racemic formulation of albendazole sulphoxide (ABZSO) were administered to pregnant rats on day 10 of gestation....
Three single oral doses (8.5, 10, and 14 mg/kg) of a racemic formulation of albendazole sulphoxide (ABZSO) were administered to pregnant rats on day 10 of gestation. Mother plasma and embryo concentrations of ABZSO enantiomers and albendazole sulphone (ABZSO(2)) were determined 9 h after administration. The (-)-ABZSO enantiomer showed higher peak concentrations in both maternal plasma and embryo than the (+) enantiomer. An increase in embryo concentrations of ABZSO enantiomers and ABZSO(2) was only observed when dose rose to 14 mg/kg. There was an increase in resorption when the dose increased, but significant differences were only found in the higher dose group when compared with the other groups. The incidence of external and skeletal malformations (mostly of the tail, vertebrae and ribs) rose significantly in the 10 mg/kg group, producing almost 20% and 90% of malformed fetuses, respectively, and gross external and skeletal abnormalities in the thoracic region and limbs were also found.
Topics: Abnormalities, Multiple; Administration, Oral; Albendazole; Animals; Anthelmintics; Bone and Bones; Embryonic and Fetal Development; Female; Limb Deformities, Congenital; Pregnancy; Rats; Rats, Sprague-Dawley
PubMed: 12672373
DOI: 10.1016/s1090-0233(02)00158-2 -
Clinical Pharmacology and Therapeutics Mar 1990We prospectively studied the effect of albendazole on microsomal reserve and on first-pass activation to albendazole sulfoxide in patients with hydatid disease. An...
We prospectively studied the effect of albendazole on microsomal reserve and on first-pass activation to albendazole sulfoxide in patients with hydatid disease. An aminopyrine breath test was performed in 12 patients while they were receiving albendazole treatment and while they were not. Excretion of 14CO2 in breath averaged 0.70%.kg.mmol-1 +/- 0.20%.kg.mmol-1 without treatment and 0.54%.kg.mmol-1 +/- 0.14%.kg.mmol-1 with treatment (p less than 0.005). Plasma levels of albendazole sulfoxide were measured 4 hours after the morning dose during the first and second half of the 4-week treatment cycles. In nine of the 12 patients albendazole sulfoxide levels decreased during the second half of the cycle by an average of 0.84 +/- 0.76 mumol/L (p less than 0.02). Transaminase levels increased in 10 of the 12 patients during long-term albendazole treatment, and major side effects, including hepatotoxicity, neutropenia, and alopecia, were observed in three patients. We conclude that albendazole partially inhibits microsomal enzyme function but induces its own metabolism. Hepatotoxicity and other possible severe side effects necessitate close therapeutic monitoring of patients who are given albendazole.
Topics: Adult; Aged; Albendazole; Aminopyrine; Breath Tests; Drug Tolerance; Echinococcosis, Hepatic; Echinococcosis, Pulmonary; Female; Humans; Liver; Liver Function Tests; Male; Microsomes; Microsomes, Liver; Middle Aged; Neutropenia; Prospective Studies
PubMed: 2311336
DOI: 10.1038/clpt.1990.38 -
International Journal of Clinical... Nov 2009To determine a population pharmacokinetic model of the antihelmintic drug, albendazole, and identify the factors influencing the pharmacokinetic parameters in patients...
OBJECTIVES
To determine a population pharmacokinetic model of the antihelmintic drug, albendazole, and identify the factors influencing the pharmacokinetic parameters in patients with neurocysticercosis.
METHODS
A prospective study was performed in 90 patients receiving 30 mg/kg/day of albendazole for 8 days. Blood samples were collected at steady state. Plasma concentrations of albendazole sulfoxide, the main active metabolite of albendazole, were determined by HPLC. The population pharmacokinetics analysis was performed using non-linear mixed-effect modeling (NONMEM). A one-compartment model with first order absorption and elimination was used.
RESULTS
Body weight was included empirically on CL/F and V/F using an allometric relationship. Although none of the investigated covariates had a significant influence on the pharmacokinetic parameters of albendazole, the final model identified two subpopulations on the bioavailability parameter. One subpopulation comprising of 27% of the total population had a bioavailability of 28%, with the remaining subpopulation defined to have complete bioavailability. The CL/F and V/F for a standard 70 kg individual was determined to be 51.6 l/h and 4560 l, respectively. Interindividual variability in CL/F was 32%; the residual unexplained variability was 32%.
CONCLUSIONS
The considerable variability reported in albendazole pharmacokinetics and plasma concentrations is likely due to issues related to bioavailability. With one-fourth of the population absorbing as little as 30% of the drug relative to others, low drug exposures might be responsible for treatment failures. Therapeutic drug monitoring may be warranted to optimize the eradication of the infecting parasite.
Topics: Adolescent; Adult; Aged; Albendazole; Anthelmintics; Biological Availability; Chromatography, High Pressure Liquid; Drug Monitoring; Female; Humans; Male; Middle Aged; Models, Biological; Neurocysticercosis; Nonlinear Dynamics; Prospective Studies; Young Adult
PubMed: 19840532
DOI: No ID Found -
International Journal of Biological... 2015Albendazole-β-cyclodextrin citrate (ABZ:C-β-CD) inclusion complex in vivo antiparasitic activity was evaluated in the parenteral phase of Trichinella spiralis...
Albendazole-β-cyclodextrin citrate (ABZ:C-β-CD) inclusion complex in vivo antiparasitic activity was evaluated in the parenteral phase of Trichinella spiralis infection in mice. An equimolar complex of ABZ:C-β-CD was prepared by spray-drying and tested in CBi-IGE male mice orally infected with L1 infective larvae. Infected animals were treated with 50 or 30mg/kg albendazole, (ABZ) equivalent amounts of the ABZ:C-β-CD complex and non treated (controls). Mice received a daily dose on days 28, 29 and 30 post-infection. A week later, larval burden and percentage of encysted dead larvae were assessed in the host by counting viable and non-viable larvae in the tongue. Complexation of ABZ with C-β-CD increased the drug dissolution efficiency nearly eightfold. At 37 days p-i, the reduction percentage in muscle larval load was 35% in mice treated with 50mg/kg/day ABZ and 68% in those given the complex. Treatment with the lower dose showed a similar decrease in parasite burden. Treated animals showed a high percentage of nonviable larvae, the proportion being significantly higher in mice receiving the complex than in control animals (72-88% vs. 11%, P=0.0032). These data indicate that ABZ:C-β-CD increases bioavailability and effectiveness of ABZ against encapsulated Trichinella larvae, thus allowing the use of small doses.
Topics: Albendazole; Animals; Antiparasitic Agents; Citric Acid; Male; Mice; Trichinella spiralis; beta-Cyclodextrins
PubMed: 25790725
DOI: 10.1016/j.ijbiomac.2015.02.049 -
European Journal of Pharmaceutical... Oct 2018The aim of the study was to improve the solubility and dissolution rate of the poorly water soluble drug albendazole via surfactant assisted media milling process....
The aim of the study was to improve the solubility and dissolution rate of the poorly water soluble drug albendazole via surfactant assisted media milling process. Preparation of a nanosuspension and then post-processing with a solidification technique applied to improve the applicability of nanosuspension in a solid dosage forms carrier. The dry nanosuspension was obtained using microcrystalline cellulose as solid carrier after tray drying at 40 °C. Both reconstitution from the solid carrier and dissolution profile studies were investigated in biorelevant Artificial Rumen Fluid (ARF) at pH = 6.50 and dissolution media at pH = 1.20 and pH = 6.80. Reconstitution studies have demonstrated that the mean hydrodynamic diameter values of albendazole crystals released from the dry suspension were nanosized (intensity weighted hydrodynamic diameter values: 200.40 ± 2.318 nm in ARF at pH = 6.50, 197.17 ± 0.208 nm in dissolution medium at pH = 6.80). Thermodynamic solubility studies have indicated a 2.98 times increase in water solubility (144.41 ± 0.09 μg/ml milled, 48.38 ± 0.01 μg/ml unmilled, 8.21 ± 0.02 μg/ml albendazole powder) in ARF at pH = 6.50, and 2.33 times in dissolution medium at pH = 6.8: (146.27 ± 0.28 μg/ml milled, 62.71 ± 0.04 μg/ml unmilled, 9.00 ± 0.01 μg/ml albendazole powder), and 13.65% increase at pH = 1.20 (1728.31 ± 3.31 μg/ml milled, 1559.41 ± 0.40 μg/ml unmilled, 1520.70 ± 1.39 μg/ml albendazole powder), dissolution rates have also increased. Atomic Force Microscopy (AFM) and Scanning Electron Microscopy (SEM) imaging investigations detected no albendazole nanocrystals on the surface of the carrier, which demonstrated the incorporation of albendazole into the microcrystalline cellulose solid carrier structure.
Topics: Albendazole; Desiccation; Drug Compounding; Humans; Nanoparticles; Solubility
PubMed: 30010031
DOI: 10.1016/j.ejps.2018.07.027 -
Journal of Analytical Toxicology 1994Albendazole is an antihelminthic agent belonging to the benzimidazole class and has been used successfully in the treatment of neurocysticercosis. We report here a...
Albendazole is an antihelminthic agent belonging to the benzimidazole class and has been used successfully in the treatment of neurocysticercosis. We report here a method for the determination of the two major albendazole metabolites in plasma, albendazole sulfone and albendazole sulfoxide. The method consists of drug extraction from 500 microL of plasma previously acidified with chloroform-isopropanol (9:1, v/v) and extract purification with n-hexane immediately before chromatographic analysis. Separation of drugs and of the internal standard (mebendazole) was performed on an RP-18 column using acetonitrile-0.25N sodium acetate buffer (3:7, v/v), pH 5.0, as the mobile phase and using detection at 290 nm.
Topics: Adolescent; Adult; Albendazole; Child; Chromatography, High Pressure Liquid; Female; Humans; Male; Middle Aged; Reproducibility of Results
PubMed: 8207939
DOI: 10.1093/jat/18.2.86 -
Annals of Tropical Medicine and... Jun 2004The pharmacokinetics of albendazole/albendazole sulphoxide and praziquantel were investigated in Thai children with Giardia infection. Twenty school-age children were... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
The pharmacokinetics of albendazole/albendazole sulphoxide and praziquantel were investigated in Thai children with Giardia infection. Twenty school-age children were randomly allocated to receive either a single oral dose of albendazole (400 mg/child) or the same dose of albendazole given concurrently with a single oral dose of praziquantel (20 mg/kg). The concentrations of albendazole/albendazole sulphoxide and praziquantel in plasma samples, collected at intervals in the first 24 h post-treatment, were then quantified using HPLC with ultra-violet detection. No significant pharmacokinetic interaction between the albendazole and praziquantel was demonstrated. For albendazole sulphoxide, the active metabolite of albendazole, there was marked inter-individual variation in the maximum plasma concentration and the 'area under the curve'. The pharmacokinetics of albendazole sulphoxide were similar whether albendazole was given alone or in combination with praziquantel.
Topics: Administration, Oral; Albendazole; Anthelmintics; Child; Drug Therapy, Combination; Female; Giardiasis; Humans; Male; Praziquantel
PubMed: 15228716
DOI: 10.1179/000349804225003398 -
The Southeast Asian Journal of Tropical... Dec 1992Human gnathostomiasis is characterized by space-occupying inflammatory lesions and/or hemorrhage as a result of the migration of, very often, a single larva of... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Human gnathostomiasis is characterized by space-occupying inflammatory lesions and/or hemorrhage as a result of the migration of, very often, a single larva of Gnathostoma spinigerum. Intermittent cutaneous migratory swellings occurring over years is the most common manifestation and the rare cerebral invasion may be fatal. There are currently no effective anthelminthics for this infection. During a double-blind randomized placebo control trial evaluating the efficacy of albendazole in cutaneous gnathostomiasis at a dosage of 400 mg twice daily for two weeks, it was observed that gnathostome larvae tended to migrate outward as a result of the treatment so that they could be recovered by excisional biopsy or by picking with a needle. In the placebo-treated group (N = 40), no such migration was observed during the 8,470 patient-days of follow-up while in the albendazole-treated group (N = 41) there was one worm in an excisional biopsy done on day 16 and two worms were removed from the skin by the patients themselves on days 8 and 0. Assuming that the period of drug exposure of the gnathostomes was the 14 days of albendazole administration plus another washout period of 7 days (equivalent to 20 half-lives of the active detectable metabolite), the total patient-days of albendazole exposure was 830. The rate of outward migration of gnathostomes in the drug treated group (3 per 830 patient-days) was significantly (p < 0.0001) higher than in the placebo group (0 per 8,470 patient-days).(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Adult; Albendazole; Animals; Double-Blind Method; Female; Gnathostoma; Humans; Male; Skin; Spirurida Infections; Treatment Outcome
PubMed: 1298079
DOI: No ID Found -
Dermatology (Basel, Switzerland) 2009
Topics: Administration, Oral; Aged; Albendazole; Antiparasitic Agents; Female; Humans; Male; Middle Aged; Scabies; Treatment Outcome
PubMed: 19060459
DOI: 10.1159/000182254 -
Biopharmaceutics & Drug Disposition Jul 2003The pharmacokinetics of the main metabolites of albendazole (albendazole sulphoxide (ABZ-SO) and albendazole sulphone (ABZ-SO2) were studied in 12 healthy human... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
The pharmacokinetics of the main metabolites of albendazole (albendazole sulphoxide (ABZ-SO) and albendazole sulphone (ABZ-SO2) were studied in 12 healthy human volunteers in a double blind design on the first and last days of oral administration of 800 mg albendazole daily for 15 days. No significant differences were observed in C(max), T(max) and V(d)/F of ABZ-SO, whereas the AUC, AUMC and T(1/2) of this metabolite were significantly reduced and Cl/F was significantly increased in multiple dosing. There were also no significant differences in the C(max), T(max), V(d)/F and T(1/2) of ABZ-SO2, whereas the AUC and AUMC of this metabolite were significantly reduced and Cl/F was significantly increased in multiple dosing. These observations suggest time dependent pharmacokinetics of albendazole (observed for ABZ-SO and ABZ-SO2), which was explained on the basis of the induction of enzymes involved in the metabolism of ABZ-SO (albendazole sulphoxide) to metabolites other than albendazole sulphone in multiple dosing.
Topics: Administration, Oral; Adult; Albendazole; Anthelmintics; Area Under Curve; Double-Blind Method; Drug Administration Schedule; Female; Half-Life; Humans; Liver; Male; Time Factors
PubMed: 12784319
DOI: 10.1002/bdd.355