Effect of Fascioliasis on the pharmacokinetic parameters of triclabendazole in human subjects.
OBJECTIVE
To study the clinical efficacy of Triclabendazole (TCBZ) on Egyptian patients infected with Fasciola and understand the effect of Fascioliasis on the pharmacokinetics of TCBZ.


METHODS
The pharmacokinetics of TCBZ administered as a single oral dose (10 mg/kg) was investigated in both infected and parasite--free Egyptian subjects. After oral administration, TCBZ is metabolized to a sulphone and sulfoxide derivatives. The latter is responsible for the fasciolicidal activity of TCBZ, and it could be used as a marker of drug bioavailability. Blood samples were collected following the oral administration, and TCBZ sulfoxide plasma concentrations were determined by a sensitive and specific HPLC method.


RESULTS
Pharmacokinetic parameters (Cmax, AUC0-48, t1/2 and tmax) for TCBZ sulfoxide were calculated. In patients; the mean Cmax was 9.11 +/- 1.3 microg/ml, the mean AUC(0-48) was 91 +/- 10.5 microg h ml(-1), the mean t1/2 was 7.4 +/- 0.6 h, and the tmax was 3.0 +/- 0.4 h. In normal subjects, the mean Cmax was 8.48 +/- 0.92 microg/ml, the mean AUC(0-48) was 85 +/- 6.55 microg h ml(-1), the mean t1/2 was 6.2 +/- 0.357 h, and the tmax was 3 +/- 0.4 h. No significant difference could be detected in the patients as compared to normal subjects, which would suggest that Fascioliasis does not affect any of the studied parameters. No eggs in faeces could be detected following TCBZ treatment. Also, most of the clinical investigations showed significant decline back to the normal ranges post-treatment which indicates complete curing and high TCBZ efficacy.


CONCLUSIONS
Fasioliasis as an infective condition widely spread in Egypt has no significant effect on the pharmacokinetic parameters of the orally administered TCBZ and at the same time it is very effective against the parasite which strongly and safely suggests the use of this medication for the treatment of this infection.
El-Tantawy
Walid H
WH
Drug Bioavailability Centre, National Organization For Drug Control &Research, Ministry of Health, Cairo, Egypt. wldhmdy@yahoo.com
Salem
Heba F
HF
Mohammed Safwat
Nirmeen A S
NA
D000293:Adolescent; D000328:Adult; D000818:Animals; D000871:Anthelmintics / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001562:Benzimidazoles / Q000493:pharmacokinetics*; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D004534:Egypt; D005209:Fasciola / Q000187:drug effects; D005211:Fascioliasis / Q000188:drug therapy*; D005243:Feces; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D010270:Parasite Egg Count; D000077682:Triclabendazole
D000871:Anthelmintics; D001562:Benzimidazoles; D000077682:Triclabendazole