Ivermectin is an effective treatment for bovine cutaneous papillomatosis

This study aimed to evaluate the effectiveness of ivermectin on the treatment of bovine cutaneous papillomatosis. Twenty-four Holstein calves between 9 and 17 months of age with cutaneous papillomatosis were placed into three groups with six in group I, and nine in groups II and III. Group I served as a control group and received no treatment. Ivermectin at a dose of 0.2 mg/kg was administered subcutaneously as a single dose to the animals in Group II and twice with 15 days intervals to animals in Group III. The first ivermectin application was considered as the 0th day Animals were monitored at 15 days intervals up to 3 months.No remission was observed in the control group (Group I). In Group II eight out of nine animals (88.8%) and in Group III seven out of nine animals (77.7%) showed complete recovery within 3 month observation period.It was concluded that ivermectin, as either single or double dose applications, is effective as a treatment for cutaneous papillomatosis.     

Oocysts, IgG levels and immunoblot patterns determined for Cryptosporidium parvum in bovine examined during a visit to a farm (northeastern Spain)

Single fecal and serum samples were individually collected from 101 bovines selected at random during a visit to a farm in northeastern Spain (Group I, 26 animals aged 2-36 days; Group II, 34 animals aged 1.5-4.5 months; Group III, 41 animals aged 20-24 months). Testing for the presence of Cryptosporidium parvum oocysts in feces (Monofluo Kit Cryptosporidium, Diagnostics Pasteur, France) indicated that 26% animals were infected (81% of Group I, 15% of Group II and 0% of Group III). Serological testing (ELISA for detection of specific anti-C. parvum IgG) indicated that 59% animals were seropositive (12% of Group I, 74% of Group II and 78% of Group III). Immunoblotting results indicate that cattle sera recognize C. parvum antigens of widely varying molecular weights and that the number of antigens recognized increases with age. Immunoblots revealed that some of the sera belonging to the Group I reacted with protein fractions between 15 and 20 kDa but none recognized the 21-23 kDa antigen. Only few sera in the Group II recognized the protein fraction between 15 and 20 kDa. The recognition of 21-23 kDa fraction was observed by four sera from uninfected and seropositive animals. Sera from all the seronegative Group II animals recognized few antigens and always with molecular weight greater than 50 kDa. Serum samples from both seropositive and seronegative animals belonging to the Group III recognized antigens with molecular weight ranging 15-20 kDa. Surprisingly, the protein fractions between 21 and 28 kDa reacted with approximately 30% of the sera from seropositive animals and only one of the nine sera from seronegative animals. The recognition of 42-46 kDa antigens increased with the age and only reacted with the sera from uninfected animals.     

The curative and antioxidative efficiency of ivermectin and ivermectin + vitamin E-selenium treatment on canine <Emphasis Type="Italic">Sarcoptes scabiei</Emphasis> infestation

The objective of the present study was to investigate the curative and antioxidative efficacy of ivermectin and ivermectin + vitamin E-selenium, and the influence of these agents on oxidative stress parameters in canines infested by Sarcoptes scabiei. Twenty two sarcoptic mites infested dogs and nine healthy dogs of 6 months to 2 years of age were divided into three groups. Group I comprised of healthy dogs (n = 9) whereas animals in group II (n = 11) and III (n = 11) were positive for scabies. Group II animals were treated with only 1% ivermectin @ 0.2 mg/kg SC whereas group III were additionally treated with Vitamin E and selenium (tocopherol 50 mg + Se 1.5 mg/ml) @0.5 ml/20 kg IM at weekly intervals for three times. Blood samples were collected on day 0 and 28 post therapy. The values for hemato-biochemical parameters and activities of antioxidant enzymes were significantly decreased (P < 0.05) whereas level of lipid peroxidation was significantly increased in all the infested dogs in comparison to the healthy dogs on day 0 which approached normalcy by day 28 post therapy. The dogs of group III showed better clinical recovery in comparison to group II at the end of therapy. Thus, administration of vitamin E and selenium in addition to standard therapy can alleviate these alterations hastening the clinical recovery of diseased dogs and can be recommended as an adjunct therapy with miticides for canine sarcoptic mange.     

Clinical effects of ivermectin in the treatment of Sarcoptes scabiei var canis in farm foxes

The efficacy of ivermectin against natural infection of the mange mite Sarcoptes scabiei var canis in foxes was evaluated. The investigations consisted of two field studies and one controlled study. In experiment 1, ivermectin was given as a single subcutaneous dose at 200 micrograms/kg in six foxes. In experiment 2, was one group, consisting of five animals, administered 200 micrograms ivermectin/kg s.c. twice with an interval of 35 days. Group two, consisting of four animals, was given one subcutaneous injection of 400 micrograms ivermectin/kg. In experiment 3, ten foxes were given 1 ml 0.2% Eqvalen s.c. (i.e. 340-440 micrograms ivermectin/kg). A control group of ten animals was not medicated. Before and after treatment a clinical evaluation and skin scraping for microscopic examination was carried out in all three experiments. The results indicated that ivermectin was a good alternative in the therapy of the Sarcoptes mange in foxes by moderate mite infection. A progressive clinical improvement of the mange lesions was evident in the treated foxes. Mites were not detected in skinscraping, except in one animal in experiment 3. It was concluded that ivermectin should be administered, in an initial dose of 400 micrograms/kg and a repeated dose of 200 micrograms/kg 2-3 weeks after the first treatment.     

Comparative efficiency of moxidectin gel or ivermectin paste for cyathostome control in young horses

Thirty-six young horses were allocated to three similar groups. Horses in Group 1 were treated with moxidectin gel on Days 0, 90, and 180, Group 2 horses received ivermectin paste on Days 0, 60, 120, and 180, and horses in Group 3 were untreated controls. All horses were maintained on a common pasture for the first 180 days. Immediately after the final scheduled deworming, each group was moved to a separate, clean pasture where it remained until Day 360. At monthly intervals, fecal egg counts, body weights, body condition scores, and pasture larval counts were measured. The cumulative costs of both deworming regimens were calculated. Young horses treated three times at 90-day intervals with moxidectin gel had significantly lower monthly fecal egg counts than untreated controls from Days 30 through 300. Horses given ivermectin paste four times at 60-day intervals had significantly lower egg counts than controls 30 days after each treatment and 60 days after the third dose. Average daily gains of treated horses were significantly greater than controls from Days 120 through 360 (moxidectin) and from Days 210 through 360 (ivermectin). Quarterly moxidectin treatments reduced egg counts more effectively and cost less than ivermectin given bimonthly.     

Role of oxytocin and/or PGF2 alpha on breeding efficiency in buffaloes

A study was conducted on 40 buffalo-cows, assigned randomly, immediately after calving into three groups: group I (n = 10) injected with saline and taken as control; group II (n = 15) received 25 mg PGF2 alpha/animal (Lutalyse); group III (n = 15) received 25 mg PGF2 alpha + 25 i.u. oxytocin/animal (Syntocinon), single i.m. dose. Oxytocin and/or PGF2 alpha significantly (P less than 0.01) shortened the interval from calving to first service (38.33 and 31.53 days for groups II and III respectively, versus 91.60 days for controls). The treatment reduced the service period (38.29 and 35.87 days for groups II and III respectively, versus 45.40 days for controls). Concomitantly a significant (P less than 0.01) decrease in the open-days post partum was achieved (76.62 and 67.40 days for groups II and III respectively, versus 137.00 days for controls). In addition, the treated buffaloes needed significantly (P less than 0.01) fewer services per conception (1.67 and 1.20 S/C for groups II and III respectively) than the untreated ones (2.70 S/C), besides a substantial improvement (P less than 0.01) in their conception rate either at 60 or 85 days post partum. Significantly improved (P less than 0.05) results were obtained in the oxytocin and PGF2 alpha treated animals, than in those receiving PGF2 alpha alone for all the previous parameters, except for the service period. Buffaloes therefore seemed to respond better to such treatment than dairy cows.     

Faecal excretion profile of moxidectin and ivermectin after oral administration in horses

A study was undertaken to evaluate and compare faecal excretion of moxidectin and ivermectin in horses after oral administration of commercially available preparations. Ten clinically healthy adult horses, weighing 390-446 kg body weight (b.w.), were allocated to two experimental groups. Group I was treated with an oral gel formulation of moxidectin at the manufacturer's recommended therapeutic dose of 0.4 mg/kg b.w. Group II was treated with an oral paste formulation of ivermectin at the recommended dose of 0.2 mg/kg b.w. Faecal samples were collected at different times between 1 and 75 days post-treatment. After faecal drug extraction and derivatization, samples were analysed by High Performance Liquid Chromatography using fluorescence detection and computerized kinetic analysis.For both drugs the maximum concentration level was reached at 2.5 days post administration. The ivermectin treatment groups' faecal concentrations remained above the detectable level for 40 days (0.6 +/- 0.3 ng/g), whereas the moxidectin treatment group remained above the detectable level for 75 days (4.3 +/- 2.8 ng/g). Ivermectin presented a faster elimination rate than moxidectin, reaching 90% of the total drug excreted in faeces at four days post-treatment, whereas moxidectin reached similar levels at eight days post-treatment. No significant differences were observed for the values of maximum faecal concentration (C(max)) and time of C(max)(T(max)) between both groups of horses, demonstrating similar patterns of drug transference from plasma to the gastrointestinal tract. The values of the area under the faecal concentration time curve were slightly higher in the moxidectin treatment group (7104 +/- 2277 ng.day/g) but were not significantly different from those obtained in the ivermectin treatment group (5642 +/- 1122 ng.day/g). The results demonstrate that although a 100% higher dose level of moxidectin was used, attaining higher plasma concentration levels and more prolonged excretion and gut secretion than ivermectin, the concentration in faeces only represented 44.3+/- 18.0% of the total parental drug administered compared to 74.3 +/- 20.2% for ivermectin. This suggests a higher level of metabolization for moxidectin in the horse.     

Effects of the Progesterone Receptor Antagonist Aglepristone on Implantation Administered on Days 6 and 7 after Mating in Rabbits

There is no safe and accurate method for early termination of pregnancy in the rabbit. So this study was carried out to determine the effect of aglepristone administration in preventing early pregnancy before implantation in this species. Twenty‐two animals (10–12 months old, New Zealand White rabbits) were naturally mated and pregnancies were confirmed in all animals by ultrasonographic examinations on day 6 after mating (5–7.5 MHz linear array transducer Dynamic Imaging Sonostar, UK) and the animals were grouped randomly: Group I & Group III: Aglepristone (Alizin^®, Virbac; 10 mg/kg, subcutaneously) was injected twice, 24 h apart, on days 6 and 7 after mating (n = 5; n = 8). Group II & Group IV: The same volume of 0.9% NaCl solution was subcutaneously injected in the same interval and served as controls (n = 5; n = 3). Ultrasonographical examination of the uterus was performed daily from day 7 to day 11 post‐mating to test aglepristone efficiency. Blood samples were collected between days 6 and 30, centrifuged at 3070 g for 10 min and stored at ?20°C. The does in aglepristone groups (Group I, III) were not pregnant whereas all animals in control groups were pregnant (Group II, IV). The does in group I & III were examined only clinically and ultrasonographically; however, does in groups III and IV were laparomized on days 6, 7, 9 and 11 post‐mating to control countable implantation sites. No implantation sites were present in group III whereas they were seen obviously in group IV. Side effects were not observed. The mean serum progesterone (P4) concentrations were not significantly different between control and treated does (p > 0.05). The results indicate that aglepristone treatment on days 6 and 7 after mating could prevent pregnancy after unwanted matings without any side effects in the rabbit. Aglepristone treatments are possibly not affecting further fertilities before implantation.     

Haemonchus contortus resistance to ivermectin and netobimin in Brazilian sheep.

Suffolk, Texel, Hampshire Down and Ile de France sheep from the municipalities of Porto Amazonas, Piraquara and Araucaria in the State of Paraná, and Bagé in the State of Rio Grande do Sul were brought to Sobral, State of Ceará, to be used in a cross-breeding project. On arrival they had clinical signs of nematode parasitosis, and one Suffolk female died. The animals were treated orally with ivermectin (0.2 mg kg-1) and fifteen days later with netobimin (20.0 mg kg-1). Neither drug reduced the egg counts (measured in eggs per gram, EPG) significantly, and this suggested that the nematodes in the sheep were resistant to the anthelmintics used. Haemonchus contortus was the species involved. The egg counts were reduced after oral treatment with trichlorfon (100.0 mg kg-1). Haemonchus contortus larvae obtained from these animals before trichlorfon treatment and passaged through two nematode-free sheep were used in a further experiment. Twenty 6- to 9-month-old nematode-free lambs were infected with the H. contortus larvae (10,000 per animal) and after the infection was confirmed, were randomly divided into four groups of five animals. Group I was orally treated with ivermectin at 0.2 mg kg-1, Group II with oral netobimin at 20.0 mg kg-1, Group III with oral trichlorfon at 100.0 mg kg-1 and Group IV was a non-treated control. Egg counts and faecal cultures were taken before dosing on the day of treatment and seven days later when all animals were necropsied and the nematodes were collected from the abomasa and counted.(ABSTRACT TRUNCATED AT 250 WORDS)     

注射国产LRH-A对产后母牛卵巢活动、发情和受胎的作用

<正> 引言 促性腺激素释放激素(GnRH)是下丘脑神经内分泌细胞分泌的一种释放激素。由于本身结构和功能上的特点,自七十年代初人工合成后,GnRH及其类似物被广泛用于牛繁殖的研究和生产中。国外有报道认为GnRH有促进产后母牛发情周期恢复,缩短产后空怀天数等作用。国内用LRH-A提早牦牛产后发情和受胎收到良好效果。     

Primary experimental infection of riverine buffaloes with Fasciola gigantica.

The clinical course of the primary experimental Fasciola gigantica infection was investigated in riverine buffalo calves of the Murrah breed. Nine male calves aged 12-15 months were randomly assigned to two groups of five (Group I) and four (Group II) animals. Each animal in Group I, was orally infected with 1000 metacercariae (mc) of F. gigantica, whereas Group II animals did not receive any infection dose and served as uninfected controls. No clinical signs of fasciolosis were observed until the sixth week post-infection (PI). Group I animals, however, developed recognised symptoms of acute fasciolosis, comprising apyrexic inappetance, anemia, poor weight gain, diarrhoea and sub-mandibular and facial oedema, respectively, from 5, 6, 8, 16 and 17 weeks PI. The signs were intermittent in nature and of variable duration. The prepatent period was of 92-97 days (mean 95.2 +/- 3.1). One of the five infected animals died on Day 147 PI. At necropsy, 36.8 +/- 11.0% of the infection dose was recovered as adult fluke population. The gross lesions were primarily biliary in nature. Group II, the uninfected controls, throughout the study period of 165 days PI, did not show any symptom and were negative for F. gigantica. The study demonstrated that the onset of adverse effects of F. gigantica on the growth and health of the infected host was mainly noted during late prepatency much before coprological prediction and diagnosis. The significance of preventive therapy against fasciolosis during prepatency has been stressed in endemic areas.     

Evaluation of the persistent efficacy of doramectin and ivermectin injectable against Ostertagia ostertagi and Cooperia oncophora in cattle

The persistent efficacy of doramectin and ivermectin injectable against moderate and high infection levels of Ostertagia ostertagi and Cooperia oncophora were evaluated in cattle. Calves were allocated to six groups of six animals. On Day 0 animals of Groups I1/I2 and D1/D2 were treated with 0.2mg/kg ivermectin and doramectin injectable, respectively. Animals of the C1, I1 and D1 groups received a daily (moderate) infection of 1000 L3 of O. ostertagi and 1000 L3 of C. oncophora, and animals of the C2, I2 and D2 groups received a daily (high) infection of 10,000 L3 of each species. The animals were infected for 21 days with both species, the infections with C. oncophora and O. ostertagi started from Days 8 and 15 post treatment, respectively. Animals were necropsied on Day 40. The calculation of the persistent activity of ivermectin and doramectin was based on the efficacy against the different developmental and adult stages of both parasites. The present study confirmed that infection levels may influence the duration of persistent efficacy of an anthelmintic. Doramectin had at the moderate infection level a persistent efficacy of at least 35 days against O. ostertagi and at least 28 days against C. oncophora; at the high infection dose persistent efficacy was somewhat shorter i.e. up to 33 days and approximately 28 days, respectively. The duration of persistent efficacy of ivermectin against O. ostertagi at the moderate infection level was between 14 and 25 days, at the high dose level up to 25 days. Persistent efficacy of ivermectin against C. oncophora could, at both infection doses, not be measured, with the present experimental design.     

The effect of dimethoate and pyrantel on vitamin C concentration in the rat liver

The aim of this study was to determine the content of vitamin C in the liver of rats exposed to dimethoate or pyrantel embonate as well as co-intoxication with both agents. Investigations were carried out in two stages. At each stage, the rats were divided into three experimental groups (I-III) and a control (C) group. In the first stage, rats from group I were administered pyrantel embonate at a two-week interval at a dose of 1/2 LD50, while the animals from group II received dimethoate for 28 days at a dose of 1/25 LD50, and those from group III - both mentioned compounds in an identical manner as in groups I and II. In the second stage, the rats from group I received pyrantel embonate at a dose of 1/5 LD50 for 3 consecutive days, while the animals from group II received dimethoate at a dose of 1/10 LD50 for 5 consecutive days, and those from III received both compounds, but pyrantel was administered on day 3, 4 and 5 of dimethoate administration. The concentration of vitamin C after pyrantel embonate and dimethoate administration was influenced not only by doses of the compounds used but also by the manner of their application (single or co-administration). Dimethoate delivered at a dose of 1/25 LD50 evoked an increase in vitamin C concentration that was observed to continue up to the 14th day after the exposure, whereas when applied at a dose of 1/10 LD50 it increased the vitamin C level only at the 3rd hour. A considerable decrease in the vitamin C level was reported after pyrantel treatment at a dose of 1/5 LD50. In rats from groups where the compounds were co-administered, increased level of vitamin C was observed at both stages of the experiment only in the first period after intoxication, i.e. up to the 6th hour.     

Induction of Abortion in Feedlot Heifers with a Combination of Cloprostenol and Dexamethasone

A field trial was conducted to assess the efficacy of a combined prostaglandin F₂α analogue (cloprostenol) and dexamethasone treatment as an abortifacient in feedlot heifers. Heifers were grouped according to stage of gestation as follows: Group I, one to four months, n = 37: group II, four to six months, n = 40: group III, six to eight months, n = 40: group IV, one to eight months, n = 29. Heifers in groups I, II and III received a simultaneous intramuscular injection of 500 μg cloprostenol and 25 mg dexamethasone at the time of rectal palpation for pregnancy diagnosis. Heifers in group IV were subjected to rectal palpation for pregnancy diagnosis but received no treatments. Heifers were observed daily for two weeks for abortion and rectal palpations were done 50 days after treatment to determine reproductive status.     

Ivermectin toxicity in 17 collies

Ivermectin is widely used in veterinary medicine as an anthelminthic and generally has a wide margin of safety, but Collies are prone to ivermectin toxicity. Two groups of Collies were presented to the University of California Veterinary Medical Teaching Hospital (VMTH) with ivermectin toxicity. The medical records of the 2 groups of Collies were reviewed retrospectively. Group I comprised 5 adult Collies that received at least 400 microg/kg ivermectin p.o. and were presented to the VMTH 3 hours after intoxication. These Collies showed marked clinical signs on presentation. Three of these dogs required mechanical ventilation and were euthanized for financial reasons; the remaining 2 dogs were comatose but recovered in 5-7 days. Group II was comprised of 12 adult Collies presented to the VMTH 2 days (n = 10) and 5 days (n = 2) after subcutaneous injection of 200-250 microg/kg ivermectin. These animals showed greater variation in severity of illness among individuals; 5 animals progressed to stupor or coma, whereas 4 animals remained ambulatory. Most of these dogs' clinical signs deteriorated from the day of intoxication until approximately day 6, from which time they showed gradual but steady improvement. All of the Collies in this group survived, but it took 3 weeks for most of them to recover. Collies suffering from ivermectin toxicity can have a severe and prolonged clinical course requiring intensive nursing care. Respiratory, cardiovascular, and nutritional support may all be required. With appropriate care, however, the prognosis for complete recovery is good.     

Anthelmintic activity of Azadirachta indica A. Juss against sheep gastrointestinal nematodes

Gastrointestinal nematode control has been performed through use of anthelmintics. However, the development of resistant populations has required research into new alternatives. There are popular reports about anti-parasitic activity of Azadirachta indica in animals and plants. The aim of this study was to evaluate the anthelmintic activity of A. indica after feeding sheep with the dried leaves. In this experiment, 40 sheep were allotted into four treatment groups. Group I received a treatment of A. indica dry leaves mixed in a concentrate at a rate of 0.1 g/kg dose for 3 months. Group II was treated with double the dose of Group I. Group III was treated with closantel (Diantel) at the manufacturer-recommended dose once at the beginning of the study and Group IV was not treated. To compare treatment effects, the following parameters were evaluated: egg count per gram of feces (EPG), worm burden, weight gain and haematocrit. EPG and worm burden results were statistically evaluated using the Kruskal-Wallis test. Haematocrit and live weight gain were submitted to analysis of variance (ANOVA) and the means evaluated by Tukey's test with 95% probability. None of the evaluated parameters of the treatment groups were statistically different when compared to the control group, demonstrating that, with the protocol used, A. indica has no anthelmintic effect.     

Comparative evaluation of hormonal protocol on the performance of crossbred cattle

A total of 60 animals (38 cows, 22 heifers) were selected and were divided into three groups of 20 animals each (containing both anoestrus and repeat breeder) in which treatment was performed for 60 days. Group I: control (farmer practice), T₁ group: group I?+?hormone (double synch), and T₂ group: group I?+?hormone (Estra double synch). The growth performances were measured in terms of body weight and average daily gain (ADG). Blood collection was done at the start and end of the experiment for assessment of blood biochemical, hematological, and reproductive status of the animals. Results revealed significant improvement in growth and reproductive performances in treatment group as compared to control group. Higher percentage of conception was achieved in group III (60%) followed by group II (55%). The least percentage was in group I (15%), i.e., in control group. So it was found that the effect of treating the reproductive-disordered animals with Estra double synch gave comparatively better result than double synch hormonal application.     

Infectious bovine keratoconjunctivitis: subconjunctival administration of a Moraxella bovis pilus preparation enhances immunogenicity

To compare the immune response elicited by 3 routes of vaccination, 36 calves were randomly allotted to 4 groups of 9 calves each. Group I was vaccinated subconjunctivally only. Group II was vaccinated concomitantly, both subconjunctivally and in the dewlap. Group III was vaccinated in the dewlap only. Group IV was not vaccinated and served as a virulence control for the Moraxella bovis culture. Calves in groups I, II, and III were given 2 inoculations with 14 days between inoculations. Twenty-one days after the last inoculation, the ventral conjunctival sac of all calves was instilled with cells of a virulent M bovis strain. After challenge exposure, all vaccinated calves (groups I, II, and III) had evidence of enhanced resistance, compared with the nonvaccinated calves. The highest to lowest gradients of immune responsiveness were: Group I greater than or equal to group II greater than group III greater than group IV. When immune criteria, such as the percentage of diseased eyes, the mean duration of infection, the severity of corneal lesions, and the serologic response were compared, groups I and II were significantly (P less than 0.05) more resistant to challenge exposure than were groups III and IV. Group III was significantly (P less than 0.05) different from group IV in severity of lesions and in serologic response. Also, the mean duration of infection was shorter, and the percentage of diseased eyes was less in group III than in group IV (P greater than 0.10). Group I was more resistant than was group II (P less than 0.10).(ABSTRACT TRUNCATED AT 250 WORDS)     

Pretreatment with the inducers rifampicin and phenobarbital alters ivermectin gastrointestinal disposition

Ballent, M., Lifschitz, A., Virkel, G., Mate, L., & Lanusse, C. Pretreatment with the inducers rifampicin and phenobarbital alters ivermectin gastrointestinal disposition. J. vet. Pharmacol. Therap. 33 , 252–259. The goal of the study was to evaluate the effects of rifampicin (RFP) and phenobarbital (PBT) on the plasma and gastrointestinal disposition kinetics of ivermectin (IVM) subcutaneously administered to Wistar rats. Fifty seven rats were used. Animals in Group I were the noninduced (control) group. Those in Groups II and III received a treatment with RFP (160 mg/day) and PBT (35 mg/day), respectively, both given orally during eight consecutive days as induction regimen. The IVM pharmacokinetic study was started 24 h after the RFP and PBT last administration. Animals received IVM (200 μg/kg) by subcutaneous injection. Rats were sacrificed between 6 h and 3 days after IVM administration. Blood and samples of liver tissue, intestinal wall and luminal content of jejunum were collected from each animal. IVM concentrations were measured by high performance liquid chromatography. IVM disposition kinetics in plasma and tissues was significantly modified by the PBT treatment, but not by RFP. Despite the enhanced CYP3A activity observed after the pretreatment with RPF and PBT, there were no marked changes on the percentages of IVM metabolites recovered from the bloodstream in induced and noninduced animals. An enhanced P‐glycoprotein‐mediated intestinal transport activity in pretreated animals (particularly in PBT pretreated rats) may explain the drastic changes observed on IVM disposition.