Vet Parasitol. 1998 Feb 28;75(2-3):209-19. Methimazole-mediated enhancement of albendazole oral bioavailability and anthelmintic effects against parenteral stages of Trichinella spiralis in mice: the influence of the dose-regime.
Lopez-Garcia ML, Torrado S, Torrado S, Martinez AR, Bolas F.
Departamento de Parasitologia, Facultad de Farmacia, Universidad Complutense, Madrid, Spain.
The influence of methimazole (MTZ) inhibitor of the microsomal oxidases on the systemic availability of the albendazole sulpho-metabolites (ABZS-MT) albendazole-sulphoxide (ABZSO) and albendazole-sulphone (ABZSO2) and on its anthelmintic effects was investigated in a mouse model for helminthic infections. Plasma concentrations of the ABZS-MT were measured by high performance liquid chromatography (HPLC) following treatment of Swiss CD-1 mice with albendazole (ABZ) alone or ABZ plus MTZ, at both single and repeated doses. The anthelmintic effects were assessed in age-matched mice similarly treated following infection with Trichinella spiralis. MTZ significantly (p < 0.01) increased the ABZS-MT plasma concentrations although the pharmacokinetic profile varied greatly according to the dose of ABZ administered. When ABZ was given at a single dose of 50 mg/kg followed by MTZ at 3 mg/kg, a cumulative effect was observed in the ABZS-MT plasma levels with pharmacokinetic parameters (Tmax = 24 h, Cmax= 30.88 microg/ml and AUC = 1120.80 microg h/ml) significantly ( p < 0.01) higher than those following administration of ABZ alone (Tmax = 3 h, Cmax = 11.00 microg/ml and AUC = 268.03 microg h/ml). This cumulative effect was absent following administration of ABZ at 100 mg/kg where, after reaching a maximum (Cmax = 27.23 microg/ml) at 3 h post-administration (Tmax), the ABZS-MTplasma levels felt down quickly to values under those obtained after administration of ABZ at the same dose, but alone (AUC = 362.15 microg h/ml vs. 340.15 microg h/ml, respectively). When ABZ was given at 50 mg/kg together with MTZ three times every
J Chromatogr B Biomed Sci Appl. 1998 May 29;709(2):273-9. Simultaneous determination of albendazole sulfoxide enantiomers and albendazole sulfone in plasma.
Lanchote VL, Marques MP, Takayanagui OM, de Carvalho R, Paias FO, Bonato PS.
Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, USP, Brazil.
A high-performance liquid chromatographic method has been developed for the simultaneous determination of albendazole sulfoxide (ABZSO) enantiomers and albendazole sulfone (ABZSO2) in human plasma. The resolution of ABZSO enantiomers and ABZSO2 was obtained on a Chiralpak AD column using hexane-isopropanol-ethanol (81:14.25:4.75, v/v/v) as the mobile phase. The drugs were detected by fluorescence (lambda(exc) = 280 nm, lambda(em) = 320 nm). The drugs were extracted from 500 microl plasma with ethyl acetate, and after solvent evaporation, the residues were dissolved in the mobile phase and chromatographed. The method was precise and accurate for the three compounds, as judged by the coefficients of variation and relative errors observed. Linear standard curves were obtained in the concentration range of 5-2500 ng/ml for ABZSO enantiomers and 1-500 ng/ml for ABZSO2. A typical plasma concentration-time profile is presented for one patient under treatment for neurocysticercosis.
Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi. 1999;17(6):390-3. [Changes in computed tomogram in cerebral parenchymal cysticercosis treated with albendazole]
[Article in Chinese]
Zhao S, Xu K.
Department of Infectious Diseases, Affiliated Hospital of Bengbu Medical College, Bangbu 233004.
AIM: To observe the changes in cerebral computed tomogram (CT) in cerebral parenchymal cysticercosis after albendazole treatment. METHODS: Cerebral CT scanning was conducted in 57 patients with cerebral cysticercosis in our hospital before, during and after albendazole treatment. RESULTS: Cerebral CT might be normal before onchospheres became cysticercariae in the brain. Small cystic lesions could turn into other CT signs of cerebral cysticercosis after albendazole treatment. CONCLUSION: Normal cerebral CT cannot rule out the disease. Small cystic lesions are the earliest pathological and active signs of the disease. Nodular focus occurs after the death of Cysticercus and calcification is the final outcome of the disease.
Trop Med Int Health. 1998 Jun;3(6):462-6. Albendazole plus praziquantel versus albendazole alone as a pre-operative treatment in intra-abdominal hydatisosis caused by Echinococcus granulosus.
Cobo F, Yarnoz C, Sesma B, Fraile P, Aizcorbe M, Trujillo R, Diaz-de-Liano A, Ciga MA.
General Surgery Department, Virgen del Camino Hospital, Pamplona, Spain. fcoboedestb.es
OBJECTIVE: To compare the effects of a combined medication of albendazole (10 mg/kg/day) plus praziquantel (25 mg/kg/day) to those of albendazole alone at different doses (10 and 20 mg/kg/day). METHOD: The protoscoleces' viability was studied in a consecutive series of patients affected by intra-abdominal hydatidosis caused by Echinococcus granulosus. In all cases the drugs were given during the month prior to surgery. RESULTS: A significant increase of patients with nonviable protoscoleces was observed in the group treated with the scolicides combination compared to those treated with albendazole alone, both at a dose of 10 mg/kg/day (P = 0.004) and at a dose of 20 mg/kg/day (P = 0.03). Albendazole sulphoxide levels in serum and in cyst fluid were higher in patients given the combined therapy than in those who received only albendazole (10 mg/kg/day: P = 0.016; 20 mg/kg/day: P = 0.034). Levels in the cysts were not significantly different probably due to the sample size; nevertheless a lineal relation between the values obtained in serum and inside the cysts could be discerned in the patients treated with the combined medication. CONCLUSION: Albendazole plus praziquantel is more effective than monotherapy with albendazole in the preoperative treatment of intra-abdominal hydatidosis.
Acta Neurol Scand. 1998 Aug;98(2):121-3. Incidence and significance of adverse effects of albendazole therapy in patients with a persistent solitary cysticercus granuloma.
Rajshekhar V.
Department of Neurological Sciences, Christian Medical College and Hospital, Vellore, India.
OBJECTIVE: To study the incidence of adverse reactions to albendazole therapy in patients presenting with seizures and a persistent (>3 months after diagnosis), solitary cysticercus granuloma and to determine whether the occurrence of adverse reactions predicted the response of the granuloma to therapy. MATERIAL AND METHODS: In a prospective study, adverse reactions were monitored in 43 patients with a persistent solitary cysticercus granuloma who were treated with albendazole therapy. Steroids were administered prophylactically to 7 patients. Response to albendazole therapy was determined on a post therapy CT scan done within 12 weeks of initiation of therapy. RESULTS: Adverse reactions in the form of headache, vomiting or recurrence of seizures including focal status epilepticus occurred in 15 (34.9%) patients. Adverse reactions occurred in 3 of the 7 patients who received steroids during therapy. The occurrence of side effects was not significantly influenced by steroid therapy (P=0.47). The granuloma responded to therapy in 20 patients (46.5%). Although the granuloma responded to therapy in a larger percentage of patients with side effects than in those without side effects (60% versus 39.3%), this difference was not statistically significant (P=0.16). CONCLUSIONS: Albendazole therapy causes adverse reactions in about a third of patients with a persistent solitary cysticercus granuloma. Occurrence of adverse reactions cannot be prevented with steroid therapy and their occurrence does not predict the response of the granuloma to therapy.
Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi. 1999;17(3):152-4. [Morpholgical, histological and histochemical observations on the effect of albendazole on encysted larvae of Trichinella spiralis in mice]
[Article in Chinese]
Chen X, Chen P, Ji F, Wang Y, Wang F, Wang F.
Department of Parasitology, Chengde Medical College, Chengde 067000.
AIM: To study the mechanism of action of albendazole on encysted larvae of Trichinella spiralis in mice. METHODS: Twelve Kunming strain mice each infected with 200 T. spiralis larvae were equally divided into two groups. Six mice of the treatment group were treated with 30 mg of albendazole/kg daily for 5 days. Morphological, histological and histochemical methods were used. RESULTS: The encysted larvae of albendazole-treated group became significantly damaged, most worms were shrunken and surrounded by inflammatory cells. Histochemical study demonstrated that the glycogen and RNA content of the larvae in the treated group was decreased, the activities of SDH, ATPase, ACP were lower than those of the control group. CONCLUSION: Albendazole can affect the physiological function of Trichinella spiralis.
Pharm Dev Technol. 1998 Aug;3(3):395-403. Complexation and solubility behavior of albendazole with some cyclodextrins.
Diaz D, Bernad Bernad MJ, Gracia Mora J, Escobar Llanos CM.
Facultad de Quimica, Departamento de Quimica Inorganica, UNAM, Mexico D.F., Mexico. daviervidor.unam.mx
The main purpose of this work was to study the albendazole-cyclodextrins complexation equilibrium and to propose a suitable excipient to improve the solubility behavior and dissolution rate of albendazole. The complexation of albendazole with four cyclodextrins, alpha-CD, beta-CD, gamma-CD, and hydroxypropylated (HP)-beta-CD, has been studied by using electronic absorption spectroscopy and molecular mechanics. The equilibrium was studied at pH 7.5 under various temperature conditions, and at pH 1.8 with HP-beta-CD at 298 K. The albendazole binding constant was the greatest for the HP-beta-CD. Both the un-ionized (Alb) and the ionized species (AlbH+) were shown to interact with HP-beta-CD. The studies at different temperatures suggest that the hydrophobic effect is the most important driving force in these systems. Moreover, the dissolution rate studies with beta- and HP-beta-CDs in the buffered aqueous solution at pH 7.5 have been accomplished and the dissolution rate was observed to increase with the cyclodextrin concentration. The solubility behavior was studied with the Higuchi and Connors method. The phase solubility and direct spectroscopy methods reveal a 1:1 inclusion complex in all of the studied cases. Molecular mechanics data show the most probable structure of the complexes.
