Resistance to thiabendazole, fenbendazole and levamisole in Haemonchus and Trichostrongylus species in sheep on a Kenyan farm

Resistance to thiabendazole (TBZ), fenbendazole (FBZ) and levamisole (LVM) in naturally acquired gastrointestinal nematode parasites in sheep was investigated on a farm where anthelmintic resistance was suspected. This was measured by both the in vitro egg hatch assay, and reductions in faecal egg and worm counts in treated animals. In the egg hatch assay, nematode eggs were incubated in various concentrations of either TBZ or LVM. The level of resistance was expressed as the drug concentration inhibiting 50% of the eggs from hatching (LC50). The nematode population had LC50 values of 0.26 microgram ml-1 TBZ and 3.12 micrograms ml-1 LVM. In the faecal egg and worm count reduction test, naturally infected sheep were treated with either TBZ (88 mg kg-1), FBZ (10 mg kg-1) or LVM (15 mg kg-1). Faecal egg and total worm counts from these sheep were then compared with counts from untreated sheep. TBZ, FBZ and LVM failed to reduce the faecal egg counts and total worm counts by more than 90%. Based on the identification of larvae from faecal cultures, the most predominant nematode species in the resistant population were Haemonchus (62%) and Trichostrongylus (28%). TBZ reduced faecal egg counts for both species by less than 90%. FBZ and LVM also reduced Haemonchus spp. eggs by less than 90%. Other nematode species numbers did not satisfy criteria for the determination of efficacy.     

EFFECTS OF A PREVENTIVE AND SUPPRESSIVE CONTROL SCHEME ON THE DEVELOPMENT OF THIABENDAZOLE-RESISTANCE IN OSTERTAGIA SPP

SUMMARY Three years after the start of an experiment to assess the merits of thiabendazole (TBZ) treatment of trichostrongylid parasites in weaner sheep, field isolates of Ostertagia spp and Trichostrongylus spp were made from weaner sheep treated under one of three treatment schemes. Treatment frequencies were “nil”, “planned” (5 or 6/year) and “regular” (every 3 weeks). In addition an isolate was taken from a group of “tracer” sheep drenched with TBZ every 10 days. Resistance to TBZ was assessed using an in vitro egg hatch assay, pre- and post-treatment faecal egg counts and a controlled anthelmintic efficiency test. Pre- and post-treatment egg counts revealed the presence of TBZ-resistance in field isolates of mixed species. Egg hatch assays indicated a level of resistance for Ostertagia spp which was proportional to the frequency of TBZ treatment. The “planned”, “regular” and “tracer” strains of Ostertagia spp had resistance ratios for eggs of 4, 13 and 15 respectively when compared to the “nil” strain. In the anthelmintic efficiency assay treatment with 44 mg kg-1 and 88 mg kg-1 of TBZ removed 82 and 96% respectively of the total Ostertagia burden (adults and larvae) from the “nil” strain and 30 and 75% respectively from the “planned” strain. The same dose rates against the “regular” and “tracer” strains and additional rates of 132 or 176 mg kg-1 against the “tracer” strain failed to reduce the Ostertagia burden significantly. Intestinal Trichostrongylus spp from all isolates were fully susceptible to TBZ at 44 mg kg-1. Levamisole at 7.0 mg kg-1 was highly effective (99% reduction) against the “tracer” strain of Ostertagia.     

The effects of benzimidazole resistance and route of administration on the uptake of fenbendazole and thiabendazole by Haemonchus contortus and Trichostrongylus colubriformis in sheep

Radiolabelled fenbendazole (FBZ) and thiabendazole (TBZ) were administered into the rumen or abomassum of sheep previously infected with benzimidazole-susceptible or resistant Haemonchus contortus and Trichostrongylus colubriformis. Plasma radioactivity was determined for 12 hours following anthelmintic administration and at the end of this time the incorporation of radiolabel into the parasites was determined.Incorporation of radiolabel from FBZ was significantly greater in susceptible than in resistant worms. However, with TBZ there was no significant difference. There were no significant differences in the incorporation between H. contortus and T. colubriformis. Incorporation of TBZ was greater than FBZ in the worms except after ruminal administration to sheep showing clinical parasitism resulting from infection with benzimidazole- susceptible worms. TBZ was administered at five times the dose rate as FBZ, and thus a lower proportion of the administered TBZ than FBZ was incorporated.With the exception of incorporation of TBZ by resistant worms, the route of administration had a major effect on incorporation by the parasites and on plasma levels. Based on plasma levels, TBZ appeared to be rapidly absorbed from both the rumen and abomasum, whereas FBZ was less readily absorbed from the rumen with the rate of absorption being markedly greater if FBZ was administered directly into the abomasum. The findings suggest that the rumen may act as a reservoir of FBZ prolonging the period of high anthelmintic concentration in the host. This may contribute to the high efficacy of this anthelmintic.     

Controlled tests on activity of contemporary parasiticides on natural infections of helminths in lambs, with emphasis on strains of Haemonchus contortus isolated in 1955.

Ten controlled tests were done between 1972 and 1989, in lambs on pasture, evaluating activity of fenbendazole (FBZ; 5 mg/kg of body weight), oxfendazole (OFZ; 3.5 and 10 mg/kg), oxibendazole (OBZ; 10 mg/kg), pyrantel pamoate (PRT; 25 mg of base/kg), and thiabendazole (TBZ; 44 and 50 mg/kg) against natural infections of helminths, with emphasis on 2 strains (A and B) of Haemonchus contortus. Strain A was phenothiazine-susceptible and strain B was phenothiazine-resistant when isolated in 1955. For approximately 10 years prior to these tests, sheep infected with both strains had been treated periodically each year with several compounds, including thiabendazole, which was used many more times than the other drugs. For this study, 4 (FBZ, OFZ, OBZ, and PRT) of the 5 compounds were evaluated in either 1 or 2 controlled tests. The fifth compound, TBZ, was used for 5 tests. Strain A H contortus was resistant to TBZ for all years tested, but more susceptible to FBZ, OFZ, OBZ, and PRT. Overall, strain B was susceptible to TBZ (with a few exceptions), and also to FBZ, OFZ, OBZ (activity less on immature forms), and PRT. Other abomasal parasites (2 species of Ostertagia and 3 of Trichostrongylus) were found in low numbers, but removal overall was good for the compounds tested. Trichostrongylus axei, found in higher numbers than species of Ostertagia and other species of Trichostrongylus, were effectively removed by all compounds in most cases. Activities of TBZ and PRT were also evaluated against several species of intestinal helminths, most of which were found in low numbers. Cooperia curticei were inconsistently removed by TBZ, but activity of PRT was effective.(ABSTRACT TRUNCATED AT 250 WORDS)     

A field evaluation of anthelmintics for control of cyathostomes of horses in Brazil

The anthelmintic efficacy of ivermectin (IVM), piperazine citrate (PPZ) and fenbendazole (FBZ) alone, and combinations of FBZ with varying dosages of PPZ, was evaluated for the control of strongyles of Mangalarga equids. In all cases of positive strongly egg counts per gram of faeces (EPG) before and after treatment, pure populations of cyathostome larvae with eight gut cells were consistently observed in faecal cultures. The faecal egg count reductions (FECR) were evaluated between Day 7 and Day 56 post-treatment. Significant differences (P less than or equal to 0.05) were found between Day 7 and Day 49 when comparing the mean EPG values of IVM with those of the other anthelmintics. PPZ alone and the combination of FBZ (7.5 mg kg-1) and PPZ (55 mg base kg-1) did not show significant differences during the trial; both groups exhibiting an FECR of greater than 90% between Day 7 and Day 30. Horses treated with the combinations of FBZ (7.5 mg kg-1) and PPZ at either 40 or 25 mg base kg-1, and with FBZ alone at either 7.5 or 15 mg kg-1, showed an FECR of less than 90% 2 weeks after treatment. The emergence of a degree of resistance of strongyles to FBZ and PPZ in a segment of the cyathostomes in this population is suggested.     

Phenothiazine in the origin of benzimidazole resistance in population-B equine strongyles

Clinical trials on a central Kentucky Thoroughbred Farm (B) during 1960-1961 involved nine test treatments of mares, yearlings and weanlings (n = 124), and compared efficacies of phenothiazine (PTZ), piperazine (PPZ), mixtures of PTZ + PPZ and thiabendazole (TBZ) for (1) percent reduction and (2) complete clearance or graded reduction of strongyle egg per gram (epg) counts. Three grades of PTZ (N.F. green, micronized purified and 2-3 microns purified) at the dose rate of 55 mg kg-1 were ineffective in six tests; reduction of strongyle epg count were low grade (26%) and complete clearance was found in only 1 of 32 horses. Piperazine alone at 88 mg base kg-1 was efficacious in two tests; epg counts were effectively reduced (98%), but complete clearance was found in only 2 of 10 horses. Several mixtures of PTZ + PPZ with various dosages of PTZ (27.5-55 mg kg-1) plus PPZ base (88 mg kg-1) were quite effective in six tests, as epg counts were reduced by 96% and complete clearance occurred in 25 of 38 horses. Four trials with TBZ at dose rates between 13 and 44 mg kg-1 in 1961 reduced epg counts by 98%, but cleared only 15 of 36 horses. These data indicated: (1) a large segment of the Farm B small strongyle population was resistant to PTZ at the outset of these observations in 1960; (2) TBZ-resistant individuals were also present in this population when TBZ was first used in 1961. During the ensuing 4-year study (1962-1965) on Farm B mares (n = 15 per year) and yearlings (n = 15-17 per year), biweekly epg and larvae per gram (lpg) counts were carried out to compare the efficacy of three treatment programs: (1) monthly doses of TBZ at 26 mg kg-1; (2) monthly doses of TBZ at 13 mg kg-1; (3) bimonthly doses of a mixture of PTZ + PPZ and carbon disulfide (CS2) at dose rates of 27.5 + 88 and 78 mg kg-1, respectively, or a mixture of PTZ + PPZ + trichlorfon (TCF) at dose rates of 27.5 + 88 + 40 mg kg-1, respectively. Emergence of a TBZ-resistant segment of the small strongyle infections was evaluated by three criteria: (1) annual mean strongyle epg counts; (2) efficacy of individual treatments for epg reductions (%); (3) complete clearance or graded reductions of strongyle epg counts.4+ PTZ-resistant small strongyles. Initial use of TBZ in 1961 produced effective epg reductions, but complete clearance data revealed the presence of TBZ-resistant small strongyles at the outset...     

Effect of feed type on the pharmacokinetic disposition of oxfendazole in sheep

The plasma concentration profiles of oxfendazole (OFZ), fenbendazole (FBZ) and FBZ sulphone (FBZ.SO2) were measured followed intraruminal administration of OFZ at 5 mg kg-1 to Merino weaners fed either dry forage or grazed on pasture lucerne clover. Plasma concentrations of OFZ and FBZ were significantly lower in sheep given the dry forage.     

A Field Evaluation of Benzimidazole and Nonbenzimidazole Drugs in a Herd of Dairy Goats

A study was conducted to investigate the efficacy of six anthelmintics in a herd of dairy goats. Pretreatment larval cultures indicated that the goats were infected with Haemonchus contortus and Trichostrongylus colubriformis. Three separate treatment regimens were administered. In each trial, mature nonlactating goats were allocated into two treatment groups and a control group. Treatment groups received thiabendazole (TBZ) or levamisole (LEV), mebendazole (MBZ) or fenbendazole (FBZ), and morantel tartrate (MOR) or ivermectin (IVR). LEV, MOR, and IVR reduced fecal strongyle egg counts by 99% to 100% of pretreatment values. The benzimidazole (BZD) drugs changed pretreatment fecal egg counts by +2% to -32%. Results of posttreatment larval culture demonstrated the presence of H contortus larvae following the administration of BZD drugs.     

Efficacy of albendazole, levamisole and fenbendazole against gastrointestinal nematodes of cattle, with emphasis on inhibited early fourth stage Ostertagia ostertagi larvae.

An experiment was conducted to compare the anthelmintic efficacy of albendazole (ABZ), levamisole (LEV) and fenbendazole (FBZ) against inhibited early fourth stage larvae (EL4) of Ostertagia ostertagi during April in Louisiana. Forty cross-bred beef heifers (average weight 165 kg) were acquired during winter and grazed on pastures contaminated with O. ostertagi and other nematodes until early April. The cattle were weighed and randomly allotted into four groups of ten animals on 6 April and treatments were administered on 7 April. Experimental groupings were: Group 1, non-treated controls; Group 2, ABZ by oral drench at 10 mg kg-1; Group 3, LEV by topical, pour-on administration to back midline at 10 mg kg-1; Group 4, FBZ by oral drench at 10 mg kg-1. Equal numbers of cattle from each group were slaughtered daily between 10 and 13 days after treatment. Mean numbers of O. ostertagi developmental stages present in untreated controls were: adults, 13,714; developing L4 (DL4), 6487; inhibited EL4, 21,719. The mean percentage of inhibited EL4 was 51.8. Smaller numbers of Haemonchus placei, Trichostrongylus axei and Cooperia spp. were recovered uniformly in control cattle. Percentage reduction values for the three compounds against O. ostertagi adults, DL4 and EL4, respectively, were: ABZ, 99.0, 95.3, 84.9; LEV, 1.0, 21.8, 32.1; FBZ, 99.2, 97.2, 97.5. Differences between ABZ and LEV EL4 counts were not significant, but in all other cases worm counts in ABZ and FBZ-treated cattle were significantly lower (P less than or equal to 0.05) than in LEV-treated and control cattle. Both ABZ and FBZ were 98-100% effective against Haemonchus adults and L4, T. axei adults, and Cooperia spp. adults and L4. LEV was 100% effective against Haemonchus adults and L4, 85.6% against T. axei, and 94.6% and 89.59% effective against Cooperia spp. adults and L4, respectively.     

Comparison of ivermectin and thiabendazole for treatment of naturally occurring nematode infections of goats in Kenya

The anthelmintic activity of thiabendazole (TBZ) at 88 mg kg-1 and ivermectin at 0.2 mg kg-1 was examined in goats with naturally-acquired nematode infections. In one experiment, a herd of 450 does was treated with TBZ or ivermectin at 4-week intervals for 9 months and efficacy was measured by reduction in faecal egg counts after each treatment. In a second experiment, 100 kids were treated with ivermectin and effectiveness measured at 2 and 4 weeks after treatment by comparison of their egg counts with those of nontreated controls. In a third experiment, efficacy of treatment with TBZ and ivermectin was determined by recovery of parasites at necropsy in a controlled test with 15 kids. The results indicated that TBZ generally did not reduce egg counts and only removed 19% of Haemonchus contortus in the controlled test. The efficacy of ivermectin approached 100% for reduction in egg counts and elimination of H. contortus. Species of Ostertagia, Trichostrongylus, Nematodirus and Oesophagostomum also were present in some subjects, but not in sufficient numbers to evaluate effectiveness of treatment.     

Characterisation of two triple resistant field isolates of Teladorsagia from Scottish lowland sheep farms

The anthelmintic resistance status of two field isolates derived from farms (farm A and B) located near Edinburgh were examined using both controlled efficacy tests (CET) and faecal egg count reduction tests (FECRT). Efficacies against fenbendazole (FBZ), levamisole (LEV) and ivermectin (IVM) and, for one isolate, against combinations of these anthelmintics and moxidectin were determined in na?ve lambs, artificially infected with the isolates and treated with the compounds at the manufacturers recommended dose rates. (FBZ, 5mg/kg bodyweight (BW); LEV, 7.5mg/kg BW; IVM, 0.2mg/kg BW; Moxidectin (MOX) 0.2mg/kg BW). In both field isolates, the predominant species found pre-treatment and the only species found post-treatment was Teladorsagia circumcincta. Resistance to FBZ, LEV and IVM was confirmed in CET and FECRT on farm A and to the latter two compounds on farm B, which had a history of benzimidazole resistance and where TBZ resistance was also demonstrated using an egg hatch assay (EHA). For the farm A isolate CET efficacies against FBZ; IVM; LEV; FBZ + IVM; FBZ + LEV; FBZ, LEV + IVM and MOX were 59, 60, 88, 94,93, 92 and 98%, respectively. The CET efficacies for the farm B isolate were 51% and 72% for LEV and IVM, respectively.     

Effect of repeated benzimidazole treatments with increasing dosages on the phenotype of resistance and the beta-tubulin codon 200 genotype distribution in a benzimidazole-resistant cyathostomin population

This study was designed to investigate the effect of repeated treatments with increasingly high fenbendazole (FBZ) dosages on the phenotype and genotype of a benzimidazole (BZ)-resistant cyathostomin population. An experimentally infected horse was treated repeatedly with FBZ dose rates between 7.5 and 30.0 mg/kg body weight (bw) over approximately 2 years. Faecal egg counts (FECs) and larval cultures were performed weekly. A total of 45 faecal egg count reduction tests (FECRTs) were analysed, revealing a high variability during the course of experiment with a mean value in faecal egg count reduction (FECR) of -17% (S.D. +/- 78). The FECR was always < 90%, providing the evidence of BZ resistance. Nine egg hatch tests were performed during the course of the experiment and revealed LD(50) values between 0.20 and 0.31 microg/ml thiabendazole (TBZ) and LD(96) values of > 0.36 microg/ml TBZ, confirming the phenotype of resistance. The LD(99) varied between 0.40 and 0.63 microg/ml TBZ. Despite consecutive treatments, no noticeable increase of the LD(50), LD(96) and LD(99) values was detected for the duration of the experiment. The molecular analysis of the codon 200 of 106 third stage larvae (L3) was carried out following repeated treatments with 30 mg FBZ/kg bw. Out of these larvae 32% were homozygous TTC/TTC, 60% showed the heterozygous TTC/TAC genotype, and 8% were homozygous TAC/TAC. The resulting allele frequencies were 62% for TTC and 38% for TAC. These findings suggest that repeated BZ treatments with increasing dosages do not alter significantly the FECRT and EHT characteristics of a BZ-resistant cyathostomin population. Furthermore, it may also be concluded that, in contrast to sheep trichostrongyles, such a selection regime does not result in beta-tubulin codon 200 TAC allele autocracy.     

A field evaluation of oxibendazole in horses infected with benzimidazole resistant small strongyles

Horses with a history of frequent benzimidazole (BZD) treatment were used in a trial to assess the effectiveness of oxibendazole (OBZ). Initial investigations established that these animals were infected with small strongyles resistant to thiabendazole (TBZ), mebendazole (MBZ), cambendazole (CBZ), oxfendazole (OXF) and fenbendazole (FBZ).The herd was subsequently divided into four groups and received TBZ, CBZ, OBZ, or no treatment. OBZ effectly reduced fecal egg counts. Similar reductions were not observed with TBZ or CBZ.     

Fenbendazole and thiabendazole in cattle: partition of gastrointestinal absorption and pharmacokinetic behaviour

Fenbendazole (FBZ) and thiabendazole (TBZ) were administered intraruminally with a single dose of an indigestible marker, chromium ethylenediaminetetra-acetate (Cr-EDTA), to cattle fitted with gastrointestinal cannulae. The amounts of anthelmintic leaving the rumen, abomasum and terminal ileum in digest a were derived by compartmental analysis of Cr-EDTA concentrations and integration of benzimidazole concentrations.
TBZ was absorbed much more rapidly from the rumen than FBZ and only about 12% of the dose left the rumen in digesta compared with 30% of the FBZ. Approximately 10% and 8% of the TBZ dose appeared at the pylorus and terminal ileum, respectively. Of the above amounts, 9% in the abomasum and practically 100% in the ileum was present as 5-OH-TBZ, indicating that metabolites of absorbed TBZ were recycled to the gastrointestinal tract. Twenty-eight percent and 52% of the FBZ appeared at the pylorus and terminal ileum, respectively, indicating a substantial recycling of absorbed drug to the small intestine. It is suggested that biliary secretion of both TBZ and FBZ and their metabolites may contribute to this recycling.
Maximal concentrations of TBZ occurred in plasma in 4 h compared with about 24 h for FBZ. TBZ and metabolites were excreted in urine much more rapidly than were FBZ and metabolites. In plasma and in each of the gastrointestinal compartments, FBZ persisted much longer than did TBZ. It was concluded that slower absorption and excretion and more extensive recycling to the gastrointestinal tract of FBZ, than of TBZ, contribute markedly to its greater potency against helminths.     

Efficacy of some anthelmintics on an ivermectin-resistant strain of Haemonchus contortus in sheep

Following evidence of reduced efficacy of ivermectin in a field population of Haemonchus contortus in Brazil, this strain of the parasite was submitted to a controlled anthelmintic test. Eighty worm-free lambs were randomly split into two groups of 40. Each lamb in the first group was infected with 5000 third stage larvae (L3) of the ivermectin-resistant strain; the remaining 40 lambs were each infected with 5000 L3 of a H. contortus strain of known susceptibility to the major groups of anthelmintic compounds used in sheep. On Day 28 post-infection, each group was subdivided according to egg counts and at random into four sub-groups of ten lambs, each of which was treated with albendazole (ABZ) at 3.8 mg kg-1, levamisole (LEV) at 7.5 mg kg-1 or ivermectin (IVM) at 0.2 mg kg-1, or was left as untreated control. At slaughter, 7 days later, all the anthelmintics reduced worm burdens in animals infected with the susceptible strain (ABZ 98.9%, LEV and IVM 100%). By contrast, in the lambs infected with the ivermectin-resistant strain, LEV was 99.8% effective, but ABZ reduced worm counts by only 14.7% and IVM by only 10.4%. Interestingly at necropsy on Day 7 post-treatment, the egg counts in the resistant strain treated with ABZ had been reduced by 92.5%, although worm counts were reduced by only 14.7%.(ABSTRACT TRUNCATED AT 250 WORDS)     

The efficacy of levamisole, and a mixture of oxfendazole and levamisole, against the arrested stages of benzimidazole-resistant Haemonchus contortus and Ostertagia circumcincta in sheep

Sheep were allowed to graze pasture that had been seeded with benzimidazole-resistant Haemonchus contortus and Ostertagia circumcincta in order to acquire a burden of arrested larvae. Following housing, sheep were dosed orally with either oxfendazole at a dose rate of 4.7 mg/kg (to confirm the benzimidazole-resistant status of the species of nematode), levamisole at a dose rate of 7.5 mg/kg, or an oxfendazole/levamisole mixture at a dose rate of 4.6 mg/kg oxfendazole and 8.1 mg/kg levamisole. The efficacies of the treatments were assessed by estimation of the arrested larval burden in the abomasum of each sheep, either at 10 or 11 days (oxfendazole and oxfendazole/levamisole mixture), or 12 or 13 days (levamisole), after treatment. Compared to the untreated controls, the protection afforded by a single dose of either levamisole or the oxfendazole/levamisole mixture was >99% against the arrested stages of both Haemonchus contortus and Ostertagia circumcincta. Treatment with oxfendazole confirmed the benzimidazole-resistance status of the two species.     

Anthelmintic activity of continuous low doses of fenbendazole into the rumen of sheep

Fenbendazole (FBZ) was continuously infused for 30 days into the rumen of 103 lambs which had mature or developing benzimidazole-susceptible or thiabendazole-resistant Haemonchus contortus and susceptible Trichostrongylus colubriformis infections. Ovicidal, larvicidal and adulticidal activities were exhibited against benzimidazole-susceptible and benzimidazole-resistant H. contortus worms by FBZ at a dose level of greater than or equal to 0.2 mg kg-1 body weight day-1. Reasonably consistent high level efficacy against H. contortus was obtained with dose levels greater than 0.4 mg kg-1. Excellent control of susceptible T. colubriformis worms was achieved with the lowest dose tested of 0.4 mg kg-1 day-1. The intraruminal infusion critical study method is a tool to determine the feasibility of incorporating a candidate anthelmintic compound in a continuous sustained-release rumen device formulation. The anthelmintic profile of FBZ obtained by low-level intraruminal administration suggests that it would be a potential candidate.     

A survey of anthelmintic resistant nematode parasites in Scottish sheep flocks

The state of anthelmintic resistance in Scottish sheep flocks was evaluated during April-August 2000 using in vitro bioassays, egg hatch assays for detecting thiabendazole (TBZ) resistance and larval development assays for levamisole, ivermectin and TBZ resistance. Anaerobic sampling kits and detailed questionnaires outlining farm demographics and current management practices were mailed to 227 Moredun Foundation member farms, replies were received from 98 farms. Kits received from 90 farms contained sufficient material to conduct one or more of the assays. A majority of the farms examined (64%) exhibited TBZ resistance but there were both farm locality and regional variations in the percentage of resistant farms. Teladorsagia was the predominant genera detected from farms. No resistance to levamisole or ivermectin was detected in any of the samples. There was no strong evidence from this survey that any of the management practices examined greatly affected TBZ resistance.     

HPLC determination and pharmacokinetics of thiabendazole and its major metabolite 5-OH thiabendazole in equine plasma

Separate high performance liquid chromatographic methods were developed for thiabendazole (TBZ) and 5-hydroxy thiabendazole (5-OH-TBZ) determination in horse plasma using 1-methyl-2-phenyl benzimidazole (MPBZ) as an internal standard. In both methods TBZ and 5-OH-TBZ were extracted from plasma using organic solvents, injected on to a C-18 column, and eluents monitored by a fluorescence detector. However, mobile phase composition, extraction solvent as well as detector wavelength differed in the two methods. The linear range for TBZ was 0.02 to 0.77 microgram ml-1 while that for 5-OH-TBZ was 0.96 to 8.0 micrograms ml-1. A commercially available TBZ oral suspension was administered to four thoroughbred horses in the following manner: days 1 and 2, 44 mg kg-1; days 4 and 5, 440 mg kg-1. Blood samples were collected during the 24 hours after administration and then analysed for TBZ and 5-OH-TBZ. Half-lives (t1/2), maximum plasma concentrations (Cmax), area under plasma concentration time curves (AUC O-alpha), and relative apparent bioavailability (F), were determined using pharmacokinetic equations. The pharmacokinetic parameters varied in the following manner: 1.16 to 13.63 hours (t1/2), 12 to 131 micrograms ml-1 X hours (AUC O-alpha), 3.33 to 8.90 micrograms ml-1 (Cmax), 1.38 to 0.12 (F) after 44 mg kg-1 and 440 mg kg-1 doses, respectively. The ratios of concentrations of TBZ to 5-OH-TBZ after oral administration of TBZ, were significantly lower for 44 mg kg-1 than 440 mg kg-1 doses.(ABSTRACT TRUNCATED AT 250 WORDS)     

A comparison of plasma metabolite levels in goats and sheep during continuous low-level administration of fenbendazole

Plasma levels of fenbendazole (FBZ) and its sulphoxide (OFZ) and sulphone (FBZ.SO₂) metabolites were measured in goats and sheep during low-level administration of FBZ given by intraruminal infusion or formulated into a urea-molasses feed supplement block (UMB). In experiment 1, 6 goats and 6 sheep were offered UMB containing 0.5 g FBZ/kg (MUMB) and individual block consumption was measured daily for 18 days. In experiment 2, some of the same animals (n=4 for each species) received FBZ by intraruminal infusion at 1, 1.5 and 3 mg/kg liveweight per day for 7 days at each dosage. FBZ, OFZ and FBZ.SO levels were determined in plasma collected every 3 days in experiment 1 and on days 4, 5 and²6 of each infusion period in experiment 2. In both experiments, higher equilibrium levels were observed for the three metabolites in sheep than in goats. Significant linear relationships were observed between the daily FBZ dosages and the plasma levels of the three metabolites in both species. The regression coefficients were significantly higher in sheep than in goats for FBZ and OFZ but not for FBZ.SO₂, and they were also significantly higher during MUMB administration than during infusion for all three metabolites in both species. FBZ is a suitable anthelmintic for incorporation into a MUMB formulation for use in livestock production systems where responses to molasses urea supplementation have been demonstrated and gastrointestinal parasitism impairs productivity. The results indicate that target dose rates for goats should be 0.75 mg/kg per day compared with 0.5 mg/kg per day for sheep.Abbreviations ANOVA analysis of variance - FBZ fenbendazole - FBZ.SO₂ fenbendazole sulphone - HPLC high-performance liquid chromatography - MUMB urea-molasses feed supplement block containing 0.5 g fenbendazole/kg - OFZ fenbendazole sulphoxide - UMB urea-molasses feed supplment block