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Table 2 Pharmacological studies of febantel and fenbendazole

From: Investigation of safety and efficacy of febantel and fenbendazole in fish and exposure assessment

Compound

Study design (species, dosage, and admin. regime)

Target parasites

Results

References

FBT

Tiger puffer (T. rubripes); 25 mg/kg bw/day for 5 day; feed

–

Tmax of FBT (4 h); Cmax (0.58 Î¼g/g); FBZ concentration in plasma was constant (i.e. 4–5 Î¼g/g) until cessation; FBT, OXF, and OXFSO2 in plasma with negligible quantities (i.e., < 1 Î¼g/g)

FSCJ [27]

FBT

Tiger puffer (T. rubripes); 25 mg/kg bw/day (Single); feed

–

FBT was only detectable at below 1.8 Î¼g/g at 4 h and absent thereafter; Tmax of total residues (FBT and its metabolites) in muscle, skin and kidney was 12 h with Cmax (~ 5.0 Î¼g/g); Tmax of total residues (FBT and its metabolites) in liver was 4 h with Cmax (29.0 Î¼g/g); residues were detectable until 72 h in plasma; 24 h in organs

FSCJ [27]

FBT

Japanese Amberjack (S. quinqueradiata & S. dumerili); 0–20 mg/kg bw/day for 5 day; feed (different three trials)

H. heterocerca and Z. japonica

No apparent avoidance to medicated feed, and no signs of toxicity in all groups; effective dose and duration of FBT were demonstrated: 10 mg/kg bw/day for 5day

Shirakashi et al. [20]

FBZ

Juvenile Rohu (Labeo ronita) infected with Dactylogyrus sp.; 20 mg/kg bw/day (single) or for 7 day (e.g. three times; 1st, 3rd, and 7th day); feed

Dactylogyrus sp.

Effective to infection of target parasite via oral admin. of FBZ at 20 mg/kg bw/day on 1st, 3rd, and 7th day

Gupta et al. [3]

FBT

Tiger puffer (T. rubripes); 0–100 mg/kg bw/day; single or 2 day, 3 day, or 5 day; feed (three experiments)

H. okamotoi

Time to peak concentration of FBT at 4 h after administration and steadily decreased after 8 h; time to peak concentration of OXF sulfone at 12 h and detected in plasma until 3d

Kimura et al. [5]

FBZ

Silver perch (Bidyanus bidyanus); bath at 10 mg/L for 48 h or feed at 75 mg kg bw/day for 6day

Lepidotrema bidyana

Significant decrease in the number of adult L. bidyana following bath (81–100%) and oral admin. (84%–98%); juvenile L. bidyana following bath (31%–68%) and oral administration (28–76%)

Forwood et al. [36]

FBT

Tiger puffer (T. rubripes); 25 mg/kg bw/day for 5 day; feed

H. okamotoi

Main metabolite in plasma is FBZ followed by OXF and OXF SO2; peak concentration (10.28 Î¼g/g at 12 h), T1/2 (12.17 h), and peak concentration of FBZ sharply decline thereafter; no. of target gill fluke was significantly decreased at 4–5d after treatment; Effective dose and duration of treating immature and mature worms were demonstrated: 25 mg/kg bw/day for 5 days and WHP for 3 weeks

Kimura et al. [34]

FBZ

Rainbow trout (O. mykiss); 25 mg/L for 3 or 12 h; 0.77, 1.5, 6.2, or 12.5 mg/L for 12 h; WB (noncirculating system)

Gyrodactylus sp.

No emergence of parasites at dosage from 1.5 to 25 mg/L

Tojo et al. [29]

OXF

Rainbow trout (O. mykiss); 25 or 200 mg/L for 3 h; WB (non-circulating system)

Gyrodactylus sp.

No anthelmintic activity at the highest concentration

Tojo et al. [29]

FBZ

Gyrodactylus sp. obtained from infected rainbow trout (O. mykiss); in vitro, 12.5 mg/L for 1 h, medium (petri dish)

Gyrodactylus sp.

No death of target parasite

Tojo et al. [29]

OXF

Gyrodactylus sp. obtained from infected rainbow trout (O. mykiss); in vitro, 200 mg/L for 1 h, medium (petri dish)

Gyrodactylus sp.

No death of target parasite

Tojo et al. [29]

FBT

Juvenile Japanese Amberjack (S.quinqueradiata or S. dumerili); 0.5–25 mg/kg bw/day for up to 10 day; WB (total seven trials)

M. seriolae

Dose of 3 mg/kg bw/day or greater for 3d is effective when FBT orally admin. at early stage of infection for preventing cyst formation and multiplication of parasites

Yanagi et al. [31]

FBT

Gyrodactylus sp. obtained from infected rainbow trout (O. mykiss);

in vitro, 1000 mg/L for 0.5 h or 1 h; medium (petri dish);

In vivo, 2.5 or 10 mg/L for 3 h; WB (noncirculating system)

Gyrodactylus sp.

100% efficacy observed when FBT treated for 1 h in vitro; no anthelmintic activities at both concentration in vivo

Santamarina et al. [28]

FBZ

Young and adult three-spined sticklebacks (G. aculeatus); 0–50 Î¼g/mL for 2 day or 6 day; bath

*tolerance test, 1–100 Î¼g/mL for 100 h; bath

*infectivity test, 50 Î¼g/mL for 6 h (single) or 3 × 2 Î¼g/mL for 6 h (36 h intervals); bath

G. anomala

Infectivity test, spore infectivity was drastically lowered (no. of infected fish from 5–7 to 1–2); deep invaginations in the anterior or posterior pole of mature spores

Günter Schmahl and Jochen Benini, [32]

FBT

Japanese Amberjack (S. quinqueradiata & S. dumerili); 0–10 mg/kg bw/day for 5 day; feed

M. seriolae

Cyst detection rate and progression of cyst formation in both species

Kawakami et al. [18]

FBT

Japanese Amberjack (S. quinqueradiata, S. dumerili); 0, 10 mg/kg bw/da for 5 day; feed (different four locations, total four trials)

H. heterocerca and Z. japonica

Decreased infection prevalence of both fish species against gill flukes

Shirakashi et al. [30]

FBT

Tiger puffer (T. rubripes); 0, 12.5, or 25 mg/kg bw/day for 5 day; feed (total six trials)

H. okamotoi

Gill fluke was eliminated up to 80% by treatment, but there was no difference between concentrations

Kimura et al. [35]

FBT

Juvenile Japanese Amberjack (S.quinqueradiata or S. dumerili); ① 0–10 mg/kg bw/day for 5day; WB (three trials)

② 10 mg/kg bw/day for (5 days + 2 days interval, 1 cycle), total 15 cycles

M. seriolae

Concentration of FBT depends on cumulative mortality at the end of experiment;

Significant decrease in cyst detection rate and progression of cyst formation after treatment; no adverse effects observed in both tests

Kawakami et al. [18]

  1. FBT febantel, FBZ fenbendazole, BL Bilirubin, TG triglyceride, CRE creatine, hpf hours post-fertilization, SOD superoxide dismutase, GST glutathione S-transferase, CAT catalase activity, AST aspartate aminotransferase, ALT alanine aminotransferase, OXF oxfendazole, OXF SO2 oxfendazole sulfone, Vd volume of distribution, WHP withdrawal period