Biomedical subjects

J Q You

Publications and source records attributed to J Q You.

At least 37 records · Page 2Linked to original sources

PubMed1992

Plasma pharmacokinetics and therapeutic efficacy of praziquantel and 4-hydroxypraziquantel in Schistosoma japonicum-infected rabbits after oral, rectal, and intramuscular administration.

The relationship between plasma level and therapeutic efficacy of praziquantel (PZQ) and its major human oxidative metabolite, 4-hydroxypraziquantel (4-OHPZQ), has been investigated in Schistosoma japonicum-infected rabbits using three different routes of PZQ administration. After intramuscular administration (20 mg/kg), the maximum level of PZQ in rabbit cardiac plasma was 1.6 +/- 1.0 micrograms/ml (mean +/- SD) 30 min after administration. After oral or rectal administration (40 mg/kg), maximum plasma levels were 0.1 +/- 0.2 microgram/ml (oral) and 0.5 +/- 0.4 micrograms/ml (rectal). The corresponding maximum 4-OHPZQ concentrations in cardiac plasma were 4.6 +/- 1.8 micrograms/ml (intramuscular), 1.7 +/- 0.5 micrograms/ml (oral), and 4.1 +/- 1.6 micrograms/ml (rectal) 2 hr after administration of PZQ. After administration of similar doses, maximum levels of PZQ in plasma from the femoral vein were 29.3 +/- 27.5 micrograms/ml (intramuscular), 0.6 +/- 1.0 microgram/ml (oral), and 0.7 +/- 0.6 microgram/ml (rectal). However, 60 min after intramuscular administration, the maximum PZQ concentration in portal venous blood was only 1.0 +/- 0.6 microgram/ml, which is substantially less than corresponding maximum portal vein levels after oral (6.8 +/- 6.5 micrograms/ml) or rectal (3.7 +/- 4.6 micrograms/ml) administration. Therapeutically, in spite of the 4-6-fold lower levels of PZQ in portal venous plasma after intramuscular administration, adult worm reduction rates in infected rabbits using the above doses were 92.2% (intramuscular), 90.1% (rectal), and 72.5% (oral), respectively, four weeks after treatment. Thus, no direct correlation between levels of PZQ in peripheral or portal venous blood and therapeutic efficacy was observed in rabbits infected with S. japonicum.

Administration, Oral↗

PubMed1991

[Uptake and release of mebendazole, albendazole and albendazole sulfoxide by secondary cysts of Echinococcus granulosus in vitro].

Mebendazole (Meb), albendazole (Alb) or albendazole sulfoxide (AlbSO) were taken rapidly in vitro by secondary cysts of Echinococcus granulosus removed out from mice infected with protoscoleces 8-9 months previously. The amounts of the drugs taken by the cysts were apparently increased followed by exposure of the cysts to the drugs at 10 micrograms.ml-1. The Alb penetrated into the cysts was distributed mainly in cyst wall, whereas the content of Meb in cyst wall was twice as much as that in cyst fluid. The distributions of AlbSO in cyst wall and cyst fluid were similar. When the cysts in the medium were exposed to Alb, some AlbSO and albendazole sulphone were detected in both cyst wall and cyst fluid, indicating that a part of Alb was metabolized by the cysts. In another experiment cysts exposed to the drug for 2 h were transferred to the medium without the drug for another 24 h. The release rates of the 3 drugs from the cysts were alike. In 1-2 h after transfer about 65-70% of the drugs absorbed by the cysts previously were released. Twenty-four hours after exposure the release rates increased to 75-85%, and the release of the drugs from the cyst wall was somewhat faster than that from cyst fluid.

Albendazole↗

PubMed1991

[Pharmacokinetics of four benzimidazoles administered intragastrically to mice infected with secondary cysts of Echinococcus granulosus].

Mice infected with secondary cysts of Echinococcus granulosus were treated ig with mebendazole (Meb), albendazole (Alb), albendazole sulfoxide (AlbSO) or albendazole sulphone (AlbSP) at equal effective dosage. The blood concentrations-time courses of the four drugs were adequately fitted to a liner one-compartment open model analysed with a modified NONLIN program, and the major pharmaco- kinetic parameters were then calculated (Table 1). When Alb was given ig to the infected mice, 76.2-84.5% of the drug absorbed was metabolized to AlbSO. There fore, the pharmacokinetics of AlbSO in Alb group was determined. After ig administration of Meb to the infected mice, the ratio of the drug contents in cyst wall to corresponding plasma concentrations of Meb was 10.6-26.9%, but much less in cyst fluid. In Alb and AlbSO groups, similar AlbSO contents in cyst wall and cyst fluid with higher ratio to plasma concentrations were observed (Fig 3). The results suggest that E granulosus cysts were more susceptible to Meb than to Alb or AlbSO, and improvement of Meb absorption would be favourable for enhancement of efficacy in the treatment of hydatid disease.

Albendazole↗

PubMed1991

Uptake and effect of praziquantel and the major human oxidative metabolite, 4-hydroxypraziquantel, by Schistosoma japonicum.

After exposure to praziquantel in vitro at a concentration of 1 microgram/ml for 0.5-2 hr, amounts of praziquantel in Schistosoma japonicum varied from 2.1 +/- 1.2 to 3.7 +/- 1.6 ng/male worm and 1.3 +/- 1.2 to 2.2 +/- 1.5 ng/female worm during the time studied. At 30 micrograms/ml, praziquantel amounts were 11-33-fold higher. However, within 2 hr after removal from a medium containing 30 micrograms/ml praziquantel, 95% of the drug was released from the parasites. When S. japonicum worm pairs were incubated in vitro with 1, 10, and 30 micrograms/ml of 4-hydroxypraziquantel, the major human oxidative metabolite of praziquantel, 0.2 +/- 0.2, 3.8 +/- 1.3, and 7.4 +/- 1.3 ng/worm pair, respectively, were found after a 2-hr incubation. 15-30-fold lower than corresponding worm pair amounts of praziquantel. In vivo, when 4- or 5-wk S. japonicum-infected mice were treated orally with praziquantel (300 mg/kg), peak concentrations of praziquantel in plasma determined by high pressure liquid chromatography were 14.7 +/- 1.5 micrograms/ml (4-wk infection) and 16.7 +/- 2.8 micrograms/ml (5-wk infection) 15 min after treatment. Corresponding in vivo worm praziquantel amounts were 1.8 +/- 0.4 ng/male worm and 2.4 +/- 1.1 ng/female worm, respectively, in the 4-wk infection and 4.6 +/- 1.6 ng/male worm and 5.6 +/- 1.2 ng/female worm in the 5-wk infection. Peak plasma concentrations of 4-hydroxypraziquantel were similar but corresponding in vivo worm amounts were 1-20-fold lower, depending on the time after drug administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

[Effect of mebendazole, albendazole and albendazole sulfoxide on glycogen contents of Echinococcus granulosus cysts in infected mice].

Mice infected with protoscoleces of Echinococcus granulosus for 8-9 months were treated ig with mebendazole (Meb) 50 mg.kg-1.d-1, albendazole (Alb) 300 mg.kg-1.d-1 or albendazole sulfoxide (AlbSO) 150 mg.kg-1.d-1 for 1-7 d. The glycogen contents of cyst wall in each drug groups were 1.0 +/- 0.6 - 1.8 +/- 0.9 mg/g, 1.1 +/- 0.9 - 1.8 +/- 0.8 mg/g and 0.8 +/- 0.5 - 1.5 +/- 0.9 mg/g, respectively, which were less than those 2.2 +/- 1.3 - 2.8 +/- 1.3 mg/g of corresponding control groups with respective glycogen reduction rates of 38-55%, 36-51% and 46-62%. After prolongation of treatment course to 10-14 d, the glycogen contents of cyst wall in Meb and AlbSO groups were further decreased, which resulted in glycogen reduction rates of 73% and 69%, respectively. No further decrease of glycogen contents in Alb groups was seen as the glycogen reduction rates sustained in 32%. Histochemical observation showed that the glycogen contents in germinal layer of the cysts decreased significantly or even disappeared during the treatment of Meb, Alb or AlbSO. The results suggested that the effects of Meb and AlbSO on mice infected with secondary cysts of E granulosus were superior to Alb as evaluated by glycogen reduction rate of cyst wall.

Albendazole↗

PubMed1990

[Uptake and distribution of [3H]praziquantel in Echinococcus granulosus cysts].

[3H]Praziquantel was absorbed rapidly by the cysts in mice infected with metacestodes of Echinococcus granulosus and treated with ig [3H]praziquantel 400 mg/kg (containing 3H 1.48 MBq). Within 24 h after treatment, 3H content in the ectocyst was 27.7-54.9% higher than that in cyst wall. The peak concentration of 3H in cyst wall and cyst fluid were 11.7-15.3% of those found in plasma. However, when the cysts were exposed to [3H]praziquantel 20 micrograms/ml (containing 3H 3.7 kBq), the 3H radioactivity in the cyst wall and cyst fluid reached equilibrium within 30 min-48 h after medication, corresponding to 45.5-63.3% of 3H radioactivity in the medium. Autoradiography showed that [3H]praziquantel entered into the germinal layer through ectocyst and laminated layer. The damage to germinal layer was related closely to deposition of the drug.

Animals↗

PubMed1989

[Effect of praziquantel and albendazole on ultrastructure of protoscolex of Echinococcus granulosus].

When protoscoleces of Echinococcus granulosus, maintained in 20% calf serum-RPMI 1640 were exposed to praziquantel 1 microgram/ml for 1-48 h, severe damages to the ultrastructure of protoscoleces were observed. The main lesions of the tegument included indistinct of the matrix, vacuolization and peeling, while vacuolization of perinuclear cytoplasma in tegumental cells, focus lysis in muscle bundles, and destruction in collection ducts and flame cells were also seen. The results suggest that the damages to the tegument, collection ducts and flame cells may interfere with the nutrition and defence functions of protoscoleces, and destroy the osmoregulatory system, which may be the major causes of death in protoscoleces during treatment with praziquantel. When protoscoleces were exposed to albendazole 20 micrograms/ml for 24-72 h, no apparent damage to the tegument was detected, except that some network-like structures appeared in the cytoplasma of tegument and parenchyma cells.

Albendazole↗

PubMed1988