A comparative kinetic study of ivermectin and moxidectin in lactating camels (Camelus dromedarius).

The plasma and milk kinetics of ivermectin (IVM) and moxidectin (MXD) was evaluated in lactating camels treated subcutaneously (0.2 mg kg(-1)) with commercially available formulations for cattle. Blood and milk samples were taken concurrently at predetermined times from 12 h up to 60 days post-administration. No differences were observed between plasma and milk kinetics of IVM, while substantial differences were noted between plasma and milk profiles of MXD in that both the maximal concentration (Cmax) and the area under concentrations curves (AUC) were three to four-fold higher for milk than for plasma. The time (Tmax) to reach Cmax was significantly faster for MXD (1.0 day) than that for IVM (12.33 days). The Cmax and the AUC were significantly higher for MXD (Cmax = 8.33 ng ml(-1); AUC = 70.63 ng day ml(-1)) than for IVM (Cmax = 1.79 ng ml(-1); AUC = 30.12 ng day ml(-1)) respectively. Drug appearance in milk was also more rapid for MXD (Tmax = 3.66 days) compared to IVM (Tmax = 17.33 days). The extent of drug exchange from blood to milk, expressed by the AUCmilk/AUCplasma ratio, was more than three-fold greater for MXD (4.10) compared to that of IVM (1.26), which is consistent with the more lipophilic characteristic of MXD. However, the mean residence time (MRT) was similar in both plasma and milk for each drug.     

Pharmacokinetics of ivermectin in the yak (Bos grunniens)

The yak (Bos grunniens) belongs to the cattle family Bovidae and lives in the mountains of China and adjacent areas. Due to the physiological adaptations of yak to its environment and the lack of data, the ivermectin pharmacokinetic was studied following a single subcutaneous dose at the recommended dose for cattle (0.2 mg kg(-1)). The observed peak plasma concentration (Cmax) was 48.93 ng ml(-1) and the time to reach Cmax (Tmax) was 0.73 day. These results show a faster rate of absorption than in cattle. The values for the absorption half-life (t(1/2a)), the distribution half-life (t(1/2alpha)) and the terminal half-life (t(1/2beta)) were 0.31, 0.74 and 4.82 days, respectively. The calculated area under the concentration-time curve (AUC) was 146.2 ng day ml(-1) and the mean residence time (MRT) was 3.57 days. The availability of ivermectin appears low in yaks in comparison to cattle but equivalent to that reported in horses and is likely to be due to physiological characteristics of this species.     

Moxidectin in cattle: correlation between plasma and target tissues disposition

The time of parasite exposure to active drug concentrations determines the persistence of the antiparasitic activity of endectocide compounds. This study evaluates the disposition kinetics of moxidectin (MXD) in plasma and in different target tissues following its subcutaneous (s.c.) administration to cattle. Eighteen male, 10-month old Holstein calves weighing 120-140 kg were subcutaneously injected in the shoulder area with a commercially available formulation of MXD (Cydectin 1%, American Cyanamid, Wayne, NJ, USA) at 200 micrograms/kg. Two treated calves were killed at each of the following times post-treatment: 1, 4, 8, 18, 28, 38, 48, 58 and 68 days. Abomasal and small intestine mucosal tissue and fluids, bile, faeces, lung, skin and plasma samples were collected, extracted, derivatized and analysed to determine MXD concentrations by high performance liquid chromatography (HPLC) with fluorescence detection. MXD was extensively distributed to all tissues and fluids analysed, being detected (concentrations > 0.1 ng/g; ng/mL) between 1 and 58 days post-treatment. MXD peak concentrations were attained during the first sampling day. MXD maximum concentration (Cmax) values ranged from 52.9 (intestinal mucosa) up to 149 ng/g (faeces). The mean residence time (MRT) in the different tissues and fluids ranged from 6.8 (abomasal mucosa) up to 11.3 (bile) days. MXD concentrations in abomasal and intestinal mucosal tissue were higher than those detected in plasma; however, there was a high correlation between MXD concentrations observed in plasma and those detected in both gastrointestinal mucosal tissues. MXD concentrations were markedly greater in the mucosa than in its respective digestive fluid (P < 0.01). MXD concentrations in skin were higher than those found in plasma (P < 0.01). Drug concentrations recovered in the dermis were greater than those detected in the hypodermal tissue (P < 0.05). Large concentrations of MXD were excreted in bile and faeces. These findings may contribute to an understanding of the relationship between the kinetic behaviour and the persistence of the antiparasite activity of MXD against different ecto-endoparasites in cattle.     

Pharmacokinetics of ivermectin in zebu Gobra (Bos indicus)

Plasma disposition kinetics of ivermectin was evaluated in a West African cattle breed. Five clinically healthy zebu Gobra cattle (Bos indicus) weighing 220-270 kg were treated (0.2 mg kg-1) with a commercially available ivermectin formulation for cattle. Blood samples were collected by jugular puncture at different times between 0.5 h and 40 days post-treatment. After plasma extraction and derivatization, samples were analysed by HPLC with fluorescence detection. Ivermectin was detected in plasma between 30 min and 20 days post-treatment. The observed peak plasma concentration (Cmax) was 46.3+/-13.8 ng ml-1 and the time to reach Cmax (t(max)) was 0.9+/-0.2 day. The values for the absorption half-life (t1/2ab) and the elimination half-life (t1/2el) were 0.3+/-0.2 and 2.8+/-0.7 days, respectively. The calculated area under the concentration-time curve (AUC) was 185.2+/-12.1 ng day ml-1 and the mean residence time (MRT) was 4.2+/-1.3 days. The availability of ivermectin is low in zebu Gobra in comparison to other breeds cattle but equivalent to that reported in the yak and is likely to be due to physiological characteristics of this breed.     

Comparative distribution of ivermectin and doramectin to parasite location tissues in cattle

Pharmacokinetic studies have been used traditionally to characterize drug concentration profiles achieved in the bloodstream. However, endectocide molecules exert their persistent and broad spectrum activity against parasites localized in many different tissues. The aim of this study was to compare the distribution of ivermectin (IVM) and doramectin (DRM) to different tissues in which parasites are found following subcutaneous administration to calves. Holstein calves weighing 120-140 kg were injected in the shoulder area with commercially available formulations of IVM (Ivomec 1% MSD AGVET, NJ, USA) (Group A) or DRM (Dectomax 1%, Pfizer, NY, USA) (Group B). Two treated calves were sacrificed at 1, 4, 8, 18, 28, 38, 48 or 58 days post-treatment. Plasma, abomasal and small intestinal fluids and mucosal tissues, bile, faeces, lung and skin samples were collected, extracted, derivatized and analyzed by high performance liquid chromatography (HPLC) with fluorescence detection to determine IVM and DRM concentrations. IVM and DRM were distributed to all the tissues and fluids analyzed. Concentrations >0.1 ng/ml (ng/g) were detected between 1 and 48 days post-treatment in all the tissues and fluids investigated. At 58 days post-treatment, IVM and DRM were detected only in bile and faeces, where large concentrations were excreted. Delayed Tmax values for DRM (4 days post-administration) compared to those for IVM (1 day) were observed in the different tissues and fluids. High IVM and DRM concentrations were measured in the most important target tissues, including skin. The highest IVM and DRM concentrations were measured in abomasal mucosa and lung tissue. Enhanced availabilities of both IVM (between 45 and 244%) and DRM (20-147%) were obtained in tissues compared to plasma. There was good correlation between concentration profiles of both compounds in plasma and target tissues (mucosal tissue, skin, and lung). Drug concentrations in target tissues remained above 1 ng/g for either 18 (IVM) or 38 (DRM) days post-treatment. The characterization of tissue distribution patterns contributes to our understanding of the basis for the broad-spectrum endectocide activity of avermectin-type compounds.     

Morantel tartrate release from a long-acting intraregional device in cattle: pharmacokinetics and gastrointestinal distribution

The pharmacokinetics and gastrointestinal distribution of morantel tartrate release from a sustained release trilaminate bolus in cattle were investigated over a 98-day period post-treatment. Six Holstein calves (125-150 kg) had permanent indwelling fistulae surgically inserted into the rumen, abomasum and terminal ileum. Samples of jugular blood, feces and ruminal, abomasal and ileal fluids were taken on days -3, 1, 4, 7, 10, 14 and weekly up to 98 days post-bolus administration. Morantel tartrate concentrations were measured by HPLC after extraction and clean-up. Morantel was not detected in plasma at any time after bolus administration. High concentrations of morantel tartrate were found in ruminal, abomasal and ileal fluids and feces over 98 days post-treatment. The morantel peak concentration (Cmax) was achieved at Day 1 post-administration in each of these compartments. The steady-state morantel concentration (Css) was achieved at approximately 10 days post-treatment and maintained for 91-98 days post-treatment in these gastrointestinal compartments. The morantel Cmax, Css, area under the zero (AUC) and first moment (AUMC) of the concentration-time curve were significantly higher (P less than 0.01) in feces than in other compartments. The in vivo drug release profile of this device has been determined. Steady-state concentrations for from 91 to 98 days have been confirmed.     

Infestivity of Psoroptes ovis on ivermectin-treated cattle

Psoroptes ovis was not transmitted by natural contact to susceptible cattle which were exposed to infested, ivermectin-treated cattle 6, 12, 14, 16, and 18 days after treatment was given. However, clinical scabies did develop in 2 calves naturally exposed to P ovis-infested, ivermectin-treated calves at 10 days after treatment was given subcutaneously (200 micrograms/kg). Psoroptes ovis was transmitted to stanchioned cattle manually exposed to 200 to 300 ml of hair and skin scrapings from infested, ivermectin-treated cattle at 6, 10, 12, 14, and 16 days after treatment was given subcutaneously (200 micrograms/kg). Scabies did not develop in cattle exposed to skin scrapings obtained from infested, treated cattle at 18 and 20 days after they were treated with ivermectin. The 14-day isolation of P ovis-infested, ivermectin-treated cattle from susceptible cattle recommended by the US Department of Agriculture, although marginal, is adequate under natural conditions to prevent transmission of scabies from treated to noninfested cattle.     

Pharmacokinetics of oral omeprazole in llamas

Gastrogard, an oral formulation of omeprazole, was given to six llamas at a dose of 4 mg/kg once a day for 6 days. Plasma samples were collected at 0, 15, 30, 45, and 60 min and 2, 3, 4, 6, 8, 12, and 24 h on days 1 and 6. Plasma omeprazole concentrations were measured by high-pressure liquid chromatography with ultraviolet detection. Pharmacokinetic parameters calculated included the area under the curve (AUC(0-infinity)), peak plasma concentration (Cmax), time of peak plasma concentration (Tmax), and terminal half-life (t(1/2)). On day 6, plasma omeprazole concentrations reached a Cmax of 0.12 microg/mL at a Tmax of 45 min. The t(1/2) of omeprazole was 2.3 h and the AUC(0-infinity) was 0.38 h x microg/mL. Plasma concentrations remained above the minimum concentration for inhibition of gastric acid secretion projected from other studies on day 6 in all the llamas for approximately 6 h. However, the AUC(0-infinity) was below the concentrations associated with clinical efficacy. It was not possible to measure oral systemic bioavailability because there was no i.v. data collected from these animals. However, using data published on the i.v. pharmacokinetics of omeprazole in llamas, oral absorption was estimated to be only 2.95%. Due to low absorption the oral dose was increased to 8 and 12 mg/kg and studies were repeated. There were no significant differences in Cmax, Tmax, or AUC(0-infinity) for either of the increased doses. These results indicate that after 6 days of treatment with doses up to 12 mg/kg, oral omeprazole produced plasma drug concentrations which are not likely to be associated with clinical efficacy in camelids.     

Breed differences on the plasma availability of moxidectin administered pour-on to calves

The pharmacokinetic profile of avermectin and milbemycin compounds is affected by different drug- and host-related factors. This work reports the influence of cattle breeds on the plasma kinetics of moxidectin (MXD) after topical (pour-on) administration. Parasite-free Aberdeen Angus and Holstein calves were treated with a commercial MXD pour-on formulation at 500 microg/kg. Blood samples were collected over a period of 35 days post-treatment and the recovered plasma was analysed by high performance liquid chromatography using fluorescence detection. MXD was detected in plasma from two hours up to 35 days post-treatment in animals from both breeds. A slow MXD absorption and delayed peak plasma concentration were observed in Aberdeen Angus compared to Holstein calves. Significant lower systemic availability (expressed as AUC) (P<0.01) and peak plasma concentration (C(max)) (P<0.05) were also observed in Aberdeen Angus calves, although the plasma mean residence time (MRT) and elimination half-lives (T(1/2el)) of MXD in both breeds were similar. The pharmacokinetic differences observed between cattle breeds contribute to explain the variability in the pattern of clinical efficacy for pour-on administered endectocide compounds reported in different field trials.     

Influence of the route of administration on efficacy and tissue distribution of ivermectin in goat

The tissue concentration and efficacy of ivermectin after per os and subcutaneous administration were compared in goats experimentally infected with Trichostrongylus colubriformis (ivermectin-susceptible strain, INRA). Infected goats (n = 24) were treated per os (n = 9) or subcutaneously (n = 9) with ivermectin, 0.2 mg/kg, or kept as not treated controls. The faecal egg counts and small intestine worm counts were determined. Ivermectin concentration was measured in the plasma, gastrointestinal tract, lung, skin or hair, liver and adipose tissues at 0, 2, 7 and 17 days post-treatment. The efficacy of ivermectin against T. colubriformis infection in goat was 98.7 and 99.9% for subcutaneous and oral administration, respectively. Ivermectin concentration declined with time and only residual concentration was measured at 17 days post-treatment in plasma and gastrointestinal tract. Ivermectin concentration was higher after subcutaneous compared to per os injection in most of the tissue examined. In skin, hair and subcutaneous adipose tissue ivermectin persisted at significant concentrations 17 days post-treatment for both routes of administration. In our experimental conditions, ivermectin provides similar efficacy against T. colubriformis after subcutaneous or per os administration in goat. However, the lower ivermectin levels in tissues after per os administration suggest that the lasting of efficacy may be shortened after per os compared to subcutaneous administration especially in animals with poor body condition in pasture where re-infection occurs quickly after anthelmintic treatment.     

Pharmacokinetics of a novel formulation of ivermectin after administration to goats

OBJECTIVE: To evaluate the pharmacokinetics of a novel commercial formulation of ivermectin after administration to goats. ANIMALS: 6 healthy adult goats. PROCEDURE: Ivermectin (200 microg/kg) was initially administered IV to each goat, and plasma samples were obtained for 36 days. After a washout period of 3 weeks, each goat received a novel commercial formulation of ivermectin (200 microg/kg) by SC injection. Plasma samples were then obtained for 42 days. Drug concentrations were quantified by use of high-performance liquid chromatography with fluorescence detection. RESULTS: Pharmacokinetics of ivermectin after IV administration were best described by a 2-compartment open model; values for main compartmental variables included volume of distribution at a steady state (9.94 L/kg), clearance (1.54 L/kg/d), and area under the plasma concentration-time curve (AUC; 143 [ng x d]/mL). Values for the noncompartmental variables included mean residence time (7.37 days), AUC (153 [ng x d]/mL), and clearance (1.43 L/kg/d). After SC administration, noncompartmental pharmacokinetic analysis was conducted. Values of the variables calculated by use of this method included maximum plasma concentration (Cmax; 21.8 ng/mL), time to reach Cmax (3 days), and bioavailability (F; 91.8%). CONCLUSIONS AND CLINICAL RELEVANCE: The commercial formulation used in this study is a good option to consider when administering ivermectin to goats because of the high absorption, which is characterized by high values of F. In addition, the values of Cmax and time to reach Cmax are higher than those reported by other investigators who used other routes of administration.     

Doramectin concentration profiles in the gastrointestinal tract of topically-treated calves: Influence of animal licking restriction

Endectocide compounds are extensively used for broad-spectrum parasite control and their topical administration to cattle is widespread in clinical practice. Pour-on formulations of moxidectin, ivermectin, eprinomectin and doramectin (DRM) are marketed internationally for use in cattle. However, variability in antiparasitic efficacy and pharmacokinetic profiles has been observed. Although the tissue distribution pattern for different endectocide molecules given subcutaneously to cattle has been described, only limited information on drug concentration profiles in tissues of parasite location after topical treatment is available. Understanding the plasma and target tissue kinetics for topically-administered endectocide compounds is relevant to optimise their therapeutic potential. The current work was designed to measure the plasma and gastrointestinal (GI) concentration profiles of DRM following its pour-on administration to calves. The influence of natural licking behaviour of cattle on DRM concentration in mucosal tissue and luminal content of different GI sections was evaluated. The trial was conducted in two experimental phases. In Phase I, the DRM plasma kinetics was comparatively characterised in free-licking and in 2-day licking-restricted (non-licking) calves. The pattern of distribution of topical DRM to mucosal and luminal contents from abomasum, duodenum, ileum, caecum and spiral colon was assessed in free-licking and non-licking calves restricted over 10 days post-administration (Phase II). The prevention of licking caused marked changes on the plasma and GI kinetics of DRM administered pour-on. In 2-day licking restricted calves, DRM systemic availability was significantly lower (29%) than in free licking animals during the first 9 days post-treatment. Following a 10-day long licking restriction period, DRM concentrations profiles in both mucosal tissue and luminal contents of the GI tract were markedly higher in animals allowed to lick freely. This enhancement in drug concentrations in free-licking compared to non-licking calves, was particularly pronounced in the abomasal (38-fold higher) and duodenal (six-fold higher) luminal content. As shown earlier for ivermectin, licking behaviour may facilitate the oral ingestion of topically-administered DRM in cattle. This would be consistent with the marked lower drug concentration profiles measured in the bloodstream and GI tract of the animals prevented from licking. The work reported here provides relevant information on the pattern of DRM distribution to the GI tract after pour-on treatment, and contributes to understand the variability observed in the antiparasitic persistence of topically-administered endectocides in cattle. The implications of natural licking in topical treatments are required to be seriously assessed to achieve optimal parasite control and to design parasitological and pharmacological studies within the drug approval process.     

Penicillin concentrations in serum, milk, and urine following intramuscular and subcutaneous administration of increasing doses of procaine penicillin G in lactating dairy cows.

Eight healthy, non-pregnant, crossbred Holstein dairy cows (557-682 kg) within their first 3 months of lactation (13-21.5 kg of milk/day) were used. Cows were kept in tie stalls for the whole experiment. The 8 cows were randomly assigned to 2 (IM and SC) 4 x 4 balanced Latin square design experiments. Doses of procaine penicillin G (PPG) (300000 IU/mL) in each square were 7000, 14000, 21000 and 28000 IU/kg and were injected IM or SC once daily for 5 consecutive days. Volumes of PPG per site of injection never exceeded 20 mL. Blood was collected to determine the Cmax, Tmax, and AUC; urine and milk were also taken to measure the persistence of PPG in these fluids. Results show that serum Cmax and Tmax were only slightly affected by increasing the doses or the route of administration, whereas the AUC was linearly increased in relation to the dose injected in both modes of injection. In the urine, Cmax varied from 160 to 388 IU/mL and Tmax from 72-120 h during 5 consecutive days of PPG injection. A dose effect in Cmax was observed only for the IM route of administration and no variation (P > 0.05) was found between the IM and SC routes. Milk Cmax concentrations were only increased by the dose regimen in the IM group. At doses of 21000 and 28000 IU/kg, the IM group had a higher (P > 0.05) Cmax when compared with the SC groups. Milk PPG residues were not detectable over 96 h following the last IM injection, independently of the dose injected. However milk PPG residues were detected for up to 132 h following the last SC injection. These results show that when PPG is injected IM once daily in volumes not exceeding 20 mL/site at doses as high as 28000 IU/kg, the withdrawal period should be at least 96 h. Therefore, in the present model, there was no advantage to inject PPG by SC route to improve PPG kinetic parameters as the AUC, Cmax, or Tmax.     

Changes of vitamin E status of periparturient dairy cows and newborn calves

Eleven primiparous Holstein Friesian and their crossbred calves (F1, Japanese Black cattle × Holstein Friesian) and 10 multiparous Holstein Friesian and their Holstein Friesian calves were used to evaluate vitamin E status in periparturient period. Plasma α‐tocopherol (α‐toc) concentrations of the multiparous cows were significantly higher than those of the primiparous cows from 60 days before expected calving to 90 days of lactation (P < 0.05). The multiparous cows had a further decrease in the concentrations of α‐toc and total lipid in plasma to the calving than the primiparous cows. Colostrum α‐toc concentrations in multiparous cows were significantly higher than those of the primiparous cows (P < 0.05). Plasma α‐toc concentrations of calves borne by the multiparous cows were significantly higher than those of the primiparous cows at 5 days of age (P < 0.05). Plasma α‐toc concentrations of calves were highest at 5 and 15 days of age in the calves borne by the multiparous and primiparous cows, respectively, and decreased thereafter till 90 days of age. The higher vitamin E status of multiparous cows over primiparous cows might have reflected nutritional composition in the rations. Their calves afforded higher plasma α‐toc levels after birth because of more α‐toc transfer via placenta and more α‐toc secretion in the colostrums thereafter. Plasma α‐toc concentrations of the calves might have decreased as the calves became dependent upon the solid feed of low vitamin E content.     

Comparison of the effects of injections of nortestosterone phenylpropionate at single and multiple sites in cattle on the detection of its residues in plasma, urine and bile

The synthetic androgen 17 beta-19-nortestosterone (beta-NT) has been used illegally as a growth promoter in cattle production in the European Union. The elimination of beta-NT and its metabolites in plasma and urine was studied in cattle which had received intramuscular injections of its phenylpropionate ester (NTPP) at either single or multiple sites at a dose rate of 1 mg/kg bodyweight. In both groups, the plasma concentrations of beta-NT, measured by enzyme immunoassay, were consistently greater than the assay's limit of quantification (0.24 ng/ml) during days 1 to 7 of the study. The mean (sd) maximum plasma concentration (Cmax) was significantly greater in the multiply injected animals (4.4 [0.48] v 2.7 [0.15] ng/ml), but other plasma pharmacokinetic parameters, AUC, CL, T1/2 beta, Tmax and MRT, were not significantly different in the two groups. The equivalent urinary concentrations exceeded the limit of quantification of the assay (4.5 ng/ml) for up to 24 days after injection. In a second study, the biliary concentrations of beta-NT and its 17 alpha-epimer (alpha-NT) were measured by gas chromatography-high resolution mass spectrometry after cattle were injected intramuscularly at either single or multiple sites with NTPP. Only alpha-NT was detected in bile for up to 62 days after injection at concentrations above the limit of quantification of the assay (0.7 ng/ml). It is concluded that in some animals, intramuscular injections of NTPP at several sites may decrease the period after injection during which free beta-NT and its metabolites are detectable in plasma and urine. After the injection of NTPP, alpha-NT was detected in bile for longer than it was detected in plasma or urine.     

Bioequivalence of ivermectin formulations in pigs and cattle

The vehicle in which endectocide compounds are formulated plays a relevant role in their absorption kinetics and resultant systemic availability. The pharmaceutical bioequivalence and comparative plasma disposition kinetics of ivermectin (IVM), following the subcutaneous administration of two injectable formulations to pigs and cattle were investigated using parallel experimental designs. Sixteen parasite-free male Duroc Jersey-Yorkshire crossbred pigs (90-110 kg) (Expt 1) and 16 parasite-free male Holstein calves (100-120 kg) (Expt 2) were divided into two groups and treated subcutaneously at either 300 (pigs) or 200 (calves) microg/kg with two different propylene glycol/glycerol formal (60: 40) based IVM formulations; in both experiments pigs or calves in Group A received the test (IVM-TEST) formulation and those in Group B were treated with the reference formulation (IVM-CONTROL). Heparinized blood samples were taken from 0 h up to either 20 (pigs) or 30 (calves) days post-treatment and plasma was extracted, derivatized and analysed by high performance liquid chromatography (HPLC) using fluorescence detection. Early detection of IVM (12 h) with a peak plasma concentration (C(max)) between 33 and 39 ng/mL was observed in pigs. The drug was detected in plasma up to 20 days post-administration of either formulation, resulting in elimination half-lives between 3.47 and 3.80 days. There were no differences between the IVM-TEST and IVM-CONTROL formulations in the kinetic parameters (except t(max)) obtained in pigs. IVM was detected in plasma between 12 h and 30 days post-administration of both formulations under investigation in cattle. The plasma disposition kinetics of IVM in calves was similar following treatment with both formulations. C(max) values (between 40.5 and 46.4 ng/mL) were achieved at 2 days post-administration of both formulations. None of the estimated kinetic parameters were statistically different between drug formulations. The injectable IVM formulations investigated were bioequivalent after their subcutaneous administration to both pigs and calves at recommended dose rates.     

Effect of growth and parturition on hair cortisol in Holstein cattle

The effect of growth and parturition on hair cortisol concentrations of cattle was investigated. Plasma, saliva, and hair (black and white from the shoulders and hip) samples were collected from calves at 6 and 24 weeks old and from dairy cattle at the dry (1 and 2 months prepartum) and lactation (10, 50, 150, and 250 days postpartum) periods. Plasma and saliva cortisol concentrations were lower in 24-week-old calves than those of 6-week-old calves, and hair cortisol concentrations decreased regardless of color and position. In 6-week-old calves, hair cortisol concentrations differed between sampling positions, but this difference was not observed in 24-week-old calves. Plasma and saliva cortisol concentrations increased before parturition until 10 days postpartum then decreased until 50 days postpartum. The same trend was observed in the cortisol concentrations of white hair. Contrarily, cortisol concentrations in black hair remained unchanged and was lower than that in white hair. Hair cortisol concentration can vary greatly depending on the location on the body, hair color, cattle age, or parturition. When this method is used, all of the above factors must be considered.     

Influence of experimentally induced theileriosis (Theileria annulata) on the pharmacokinetics of a long-acting formulation of oxytetracycline (OTC-LA) in calves

The effects of experimental Theileria annulata infection on the i.m. (20 mg/kg) pharmacokinetics of oxytetracycline were investigated in crossbred calves. The serum concentration-time curves of oxytetracycline (OTC-LA), before and after experimental infection, were best described by a one-compartment open model. The experimental infection by subcutaneous administration of ground-up tick supernate (GUTS), equivalent to 30 Hyalomma anatolicum anatolicum ticks infected with Theileria annulata, produced a clear temperature rise and signs of clinical disease in calves. Subsequently, haemoglobin, packed cell volume, total leucocyte count and serum Cu, Fe and Zn concentrations decreased after infection. The absorption and elimination half-lives (t1/2 Ka and t1/2 Ke), mean absorbance time (MAT), time to peak concentration (Tmax), mean residence time (MRT), area under the serum concentration time curve (AUC infinity) and the bioavailability (F) were significantly (P < 0.05) decreased. The peak serum concentration (Cmax), however, remained unchanged after infection. These changes may necessitate alterations in the dosage regimen of oxytetracycline used to treat Theileria annulata infections in cattle under field conditions.     

Pharmacokinetics of ivermectin in llamas (Lama glama)

The pharmacokinetic behaviour of ivermectin was investigated in adult llamas (Lama glama) by using high performance liquid chromatography with a lower limit of quantification of 2 ng/ml to measure its concentration in serum. Llamas were treated with one of three commercial formulations (injectable, pour-on or oral paste) at dosages recommended by the manufacturer, or with an experimental injectable sustained-release formulation. In five llamas given 1 per cent ivermectin subcutaneously at 200 microg/kg, the median peak serum concentration (Cmax) was 3 ng/ml and the area under the serum concentration-time curve (AUC) was 13.5 ng x day/ml. In six llamas treated topically with 0.5 per cent ivermedin pour-on at 500 microg/kg, Cmax was 2.5 ng/ml or less and the AUC was 7.75 ng x day/ml or less. In seven llamas with measurable concentrations of ivermedin, the median times to peak serum concentration (tmax) were six days after subcutaneous injection and seven days after treatment with the pour-on formulation. In six llamas, the serum concentration of ivermectin remained less than 2 ng/ml for 124 hours after treatment with a 1.87 per cent oral paste at 200 microg/kg. In five llamas treated subcutaneously with 25 per cent ivermectin sustained-release microspheres at 1500 microg/kg, the median Cmax was 5 ng/ml and the median AUC was 224 ng x day/ml.     

Comparison of fluoroquinolone pharmacokinetic parameters after treatment with marbofloxacin, enrofloxacin, and difloxacin in dogs

Plasma, urine, and skin drug concentrations were determined for dogs (n=12) given five daily oral doses of marbofloxacin (MAR) (2.75 mg/kg), enrofloxacin (ENR) (5.0 mg/kg) or difloxacin (DIF) (5.0 mg/kg). Concentrations of the active metabolite of ENR, ciprofloxacin (CIP), were also determined. The three-period, three-treatment crossover experimental design included a 21-day washout period between treatments. Area under the plasma drug concentration vs. time curve (AUC0-last, microg/mLxh of MAR was greater than for ENR, CIP, ENR/CIP combined, and DIF. Maximum concentration (Cmax) of MAR was greater than ENR, CIP, and DIF. Time of maximum plasma concentration (Tmax) was similar for MAR and DIF; Tmax occurred earlier for ENR and later for CIP. Plasma half-life (t1/2) of MAR was longer than for ENR, CIP, and DIF. Urine concentrations of DIF were less than MAR or ENR/CIP combined, but urine concentrations of MAR and ENR/CIP combined did not differ. DIF skin concentrations were less than the concentrations of MAR or ENR/CIP combined 2 h after dosing, but skin concentrations of MAR and ENR/CIP combined did not differ.