Table 3.

Pharmacokinetic Properties of Benzimidazoles.

Drug	Absorption	Distribution	Metabolism	Excretion	Ref.
Albendazole	·<5% ·Poor solubility, as well as low absorption and bioavailability. ·High inter-variabilities of peak levels. ·A dose of 400 mg p.o. led to a Cmax of 0.16–1.58 mg/L for ABZSO. ·Tmax of ABZ was <2–3 h. ·Fat in the diet increased the absorption up to 6.5-fold. ·Tmax of ABZSO was 4.75 h. ·Cmax of ABZSO was 1.20 ± 0.44 μg/mL. ·Cmax of ABZ was 12.5 [0.047 µM] to 26.5 ng/mL [0.1 µM].	·ABZSO was widely distributed. About 70% of ABZSO was bound to plasma proteins, whereas about 90% of ABZ was bound to them. ·ABZSO crossed the BBB. ·ABZSO enantiomers were distributed about two-fold higher in the plasma than in the cerebrospinal fluid, in humans. ·When treated with 400 mg ABZ, a small amount of ABZ was detected in the serum from 2–8 h after administration. ·ABZSO was detected until 72 h in the blood.	·ABZ is metabolized to ABZSO by very rapid first-pass metabolism, and finally to ABZ sulfone through further conversion. ·Metabolism is carried out by cytochrome P450 and other oxidases, including flavin-monooxygenase. ·ABZSO has two enantiomers in the human plasma. (+)-ABZSO is the predominant enantiomeric form in the human plasma. ·Increased CYP1A expression can cause auto-inductive effect of ABZ, upon repeated administration of ABZ.	·T1/2 of ABZSO is 8–14 h. ·T1/2 of ABZ is <1.5 h. ·ABZ and its metabolites are excreted in the urine and feces. ·ABZSO is excreted in the urine quickly, from 4–72 h after administration. ·ABZ concentrations are too low to measure in the urine.	[81,94,96,99,100,101]
Fenbendazole	-	-	·FBZ is metabolized to FBZSO by first-pass metabolism, and finally to FBZ sulfone by means of further conversion. ·Metabolism is carried out by cytochrome P450 and flavin-monooxygenase. ·FBZSO has two enantiomers in the human plasma.	·FBZ and its metabolites are excreted in the urine and feces.	[99]
Flubendazole	·Poor solubility as well as low absorption and bioavailability. ·A dose of 2 g p.o. led to a Cmax that was lower than 5 ng/mL [0.016 µM] for FLZ. ·Administration after a meal increases absorption.	-	·Initial biotransformation takes place through first-pass metabolism.	·FLZ is excreted in the feces (more than 80%) and urine. ·T1/2 in tissues is 1–2 d.	[95]
Mebendazole	·5–10% and 17–22% ·poor solubility. ·Fat in the diet increased the absorption more than 5-fold. ·Cmax of MBZ was 137.4 ng/mL [0.47 µM], at a dose of 10 mg/kg. ·Tmax of MBZ was 2–4 h. ·High inter-variabilities of peak levels.	·90–95% of it existed as bound to plasma proteins.	·MBZ is metabolized by extensive first-pass metabolism to many unidentified metabolites. ·It is unclear which enzymes carry out this metabolism.	·MBZ and its metabolites are excreted in the feces and urine. ·T1/2 is 3–6 h.	[14,81,96,97]
Oxfendazole	·Poor solubility, but higher than that of ABZ or FBZ. ·Cmax of OFZ was 6770 ng/mL [21.5 µM], at a dose of 60 mg/kg. ·Tmax of OFZ was 2–3 h. ·Fat in the diet increased the Cmax by 49%, and AUC by 86%.	-	·OFZ is metabolized to OFZ sulfone, FBZ, OFZ sulfate conjugates, and OFZ glucuronide conjugates.	·Minimal amount (<1% of dose) of OFZ is excreted in the urine. ·T1/2 is 8.5–11 h.	[93,98]

Abbreviations: ABZ: albendazole; ABZSO: ABZ sulfoxide; T_max: time to peak drug concentration; C_max: maximum concentration; BBB: blood-brain barrier; FBZ: fenbendazole; FBZSO: FBZ sulfoxide; p.o.: oral administration; FLZ: flubendazole; T_1/2: half-life time; MBZ: mebendazole; OFZ: oxfendazole; AUC: area under the concentration-time curve.