Comparative plasma dispositions of ivermectin and doramectin following subcutaneous and oral administration in dogs

This study evaluates the comparative plasma dispositions of ivermectin (IVM) and doramectin (DRM) following oral and subcutaneous administration (200 microg/kg) over a 40-day period in dogs. Twenty bitches were allocated by weight in to four groups (Groups I-IV) of five animals each. Animals in the first two groups (Groups I and II) received orally the injectable solutions of IVM and DRM, respectively, at the dose of 200 microg/kg bodyweight. The other two groups (Groups III and IV) received subcutaneously injectable solutions at the same dose rate. Blood samples were collected between 1h and 40 days after treatment and the plasma samples were analysed by high performance liquid chromatography (HPLC) using fluorescence detection. The results indicated that IVM produced a significantly higher maximum plasma concentration (C(max): 116.80+/-10.79 ng/ml) with slower absorption (t(max): 0.23+/-0.09 day) and larger area under the concentration versus time curve (AUC: 236.79+/-41.45 ng day/ml) as compared with DRM (C(max): 86.47+/-19.80 ng/ml, t(max): 0.12+/-0.05 day, AUC: 183.48+/-13.17 ng day/ml) following oral administration of both drugs; whereas no significant differences were observed on the pharmacokinetic parameters between IVM and DRM after subcutaneous administrations. In addition, subcutaneously given IVM and DRM presented a significantly lower maximum plasma concentration (C(max): 66.80+/-9.67 ng/ml and 54.78+/-11.99 ng/ml, respectively) with slower absorption (t(max): 1.40+/-1.00 day and 1.70+/-0.76 day, respectively) and larger area under the concentration versus time curve (AUC: 349.18+/-47.79 ng day/ml and 292.10+/-78.76 ng day/ml, respectively) as compared with the oral administration of IVM and DRM, respectively. No difference was observed for the terminal half-lives ((t(1/2lambda(z)) and mean residence times (MRT) of both molecules. Considering the pharmacokinetic parameters, IVM and DRM could be used by the oral or subcutaneous route for the control of parasitic infection in dogs.     

Pharmacokinetics of moxidectin and doramectin in goats.

The pharmacokinetic behaviour of doramectin after a single subcutaneous administration and moxidectin following a single subcutaneous or oral drench were studied in goats at a dosage of 0.2 mg kg(-1). The drug plasma concentration-time data were analysed by compartmental pharmacokinetics and non-compartmental methods. Maximum plasma concentrations of moxidectin were attained earlier and to a greater extent than doramectin (shorter t(max) and greater C(max) and AUC than doramectin). MRT of doramectin (4.91 +/- 0.07 days) was also significantly shorter than that of moxidectin (12.43 +/- 1.28 days). Then, the exposure of animals to doramectin in comparison with moxidectin was significantly shorter. The apparent absorption rate of moxidectin was not significantly different after oral and subcutaneous administration but the extent of absorption, reflected in the peak concentration (C(max)) and the area under the concentration-time curve (AUC), of the subcutaneous injection (24.27 +/- 1.99 ng ml(-1) and 136.72 +/- 7.35 ng d ml(-1) respectively) was significantly greater than that of the oral administration (15.53 +/- 1.27 ng ml(-1) and 36.72 +/- 4.05 ng d ml(-1) respectively). The mean residence time (MRT) of moxidectin didn't differ significantly when administered orally or subcutaneously. Therefore low oral bioavailability and the early emergence of resistance in this minor species may be related. These results deserve to be correlated with efficacy studies for refining dosage requirements of endectocides in this species.     

Pharmacokinetics and efficacy of triclabendazole in goats with induced fascioliasis

The pharmacokinetics of triclabendazole were evaluated in normal goats and in goats artificially infected with Fasciola hepatica. Triclabendazole and its metabolites were determined using a novel high performance liquid chromatographic method with fluorimetric detection after solid-phase extraction. In normal goats triclabendazole given orally was metabolized rapidly to its sulphoxide and sulphone derivatives. The maximum plasma concentrations for the sulphoxide and sulphone were similar ranging from 9 to 19 micrograms/ml and these were attained at an average 12.8 and 25.6 h, respectively, after administration. Both metabolites were eliminated slowly from plasma with elimination half-lives of 22.4 h for the sulphoxide and 19.4 h for the sulphone. They persisted at measurable concentrations in plasma for up to seven days. In milk, the two metabolites occurred in low concentrations and none of them was detectable (sulphoxide less than 0.04 microgram/ml, sulphone less than 0.02 microgram/ml) after seven days. The pharmacokinetic behaviour of triclabendazole was not altered in animals with fascioliasis. Efficacy of the drug against immature (six-week) F. hepatica was 100%.     

Comparative pharmacokinetics of marbofloxacin in healthy and Mannheimia haemolytica infected calves

The pharmacokinetics of marbofloxacin were investigated in healthy (n=8) and Mannheimia haemolytica naturally infected (n=8) Simmental ruminant calves following intravenous (i.v.) and intramuscular (i.m.) administration of 2 mg kg(-1) body weight. The concentration of marbofloxacin in plasma was measured using high performance liquid chromatography with ultraviolet detection. Following i.v. administration of the drug, the elimination half-life (t(1/2 beta)) and mean residence time (MRT) were significantly longer in diseased calves (8.2h; 11.13 h) than in healthy ones (4.6 h; 6.1 h), respectively. The value of total body clearance (CL(B)) was larger in healthy calves (3 ml min(-1) kg(-1)) than in diseased ones (1.3 ml min(-1) kg(-1)). After single intramuscular (i.m.) administration of the drug, the elimination half-life, mean residence time (MRT) and maximum plasma concentration (C(max)) were higher in diseased calves (8.0, 12 h, 2.32 microg ml(-1)) than in healthy ones (4.7, 7.4 h, 1.4 microg ml(-1)), respectively. The plasma concentrations and AUC following administration of the drug by both routes were significantly higher in diseased calves than in healthy ones. Protein binding of Marbofloxacin was not significantly different in healthy and diseased calves. The mean value for MIC of marbofloxacin for M. haemolytica was 0.1+/-0.06 microg ml(-1). The C(max)/MIC and AUC(24)/MIC ratios were significantly higher in diseased calves (13.0-64.4 and 125-618 h) than in healthy calves (8-38.33 and 66.34-328 h). The obtained results for surrogate markers of antimicrobial activity (C(max)/MIC, AUC/MIC and T > or = MIC) indicate the excellent pharmacodynamic characteristics of the drug in diseased calves with M. haemolytica, which can be expected to optimize the clinical efficacy and minimize the development of resistance.     

Pharmacokinetic behavior and pharmacokinetic/pharmacodynamic integration of marbofloxacin after subcutaneous administration in goats

The pharmacokinetic behavior of marbofloxacin was studied in goats after single-dose subcutaneous (SC) administration of 2mg/kg bodyweight. Drug concentration in plasma was determined by high performance liquid chromatography and the data obtained were subjected to non-compartmental kinetic analysis. Marbofloxacin peak plasma concentration (C(max)=1.77+/-0.24microg/mL) was reached 1.25+/-0.50h (T(max)) after SC administration. The elimination half-life (t(1/2beta)) and area under curve (AUC) were 5.74+/-1.21h and 8.15 vs 2.33microg h/mL, respectively. Taking into account the values obtained for the efficacy indices, it was concluded that a SC dose of 2mg/kg/24h of marbofloxacin could be adequate to treat infections caused by high susceptible bacteria like Escherichia coli or Salmonella spp.     

The pharmacokinetic behaviour of marbofloxacin in Eurasian buzzards (Buteo buteo) after intraosseous administration

This study reports on the administration of a single dose of marbofloxacin (2 mg/kg) to five adult Eurasian buzzards (Buteo buteo) by the intraosseous (IO) route, which has been proposed as a rapid and efficient means for the parenteral delivery of antimicrobial drugs. The drug was rapidly absorbed. Peak marbofloxacin concentration (C(max)) in plasma and area under the concentration-time curve (AUC) of 1.92+/-0.78 microg/mL and 8.53+/-2.73 microg h/mL, respectively. The time marbofloxacin remained in the plasma after IO administration was relatively short (elimination half-life, t(1/2beta)=4.91+/-0.65 h; mean residence time (MRT)=5.38+/-0.57 h). Single dose marbofloxacin gave values for C(max)/minimum inhibitory concentration (MIC) of 19.2 and an AUC/MIC value of 85.3h after IO administration. The IO route appears to be practical and effective for the rapid delivery of marbofloxacin to buzzards.     

Placental transfer of albendazole sulphoxide enantiomers in sheep

Albendazole sulphoxide (ABZSO) is an anthelmintic drug used in veterinary practice. Its molecule has a chiral centre in the sulphur atom and racemic formulations are always used. The kinetics of the ABZSO enantiomers in the last third of pregnancy in ewes, and the placental transfer to the fetus, were studied after a single-dose oral administration (7.5 mg/kg) of a racemic formulation. In mothers, the area under the plasma concentration-time curve (AUC) and C(max) values of (+)-ABZSO (42.4+/-10.5 microg/mL and 1.9+/-0.4 microg/mL, respectively) were higher than those of (-)-ABZSO (15.3+/-5.1 microg/mL and 1.0+/-0.3 microg/mL). The MRT values were 17.0+/-1.6 h for (+)-ABZSO and 13.1+/-1.8 h for (-)-ABZSO. Similar kinetic parameters were obtained in the fetus for both enantiomers, but the fetal concentrations were lower compared with values for the dam. The AUC ratio between (-)-ABZSO/(+)-ABZSO in the dam was 0.36 and in the fetuses 0.64, indicating a higher impairment for the (+)-enantiomer in its placental transfer to the fetus.     

Effects of dietary variations on plasma concentrations of oral flukicides in sheep

Groups of parasite-free lambs which were either housed and fed hay arid concentrates or were grazing on pasture were dosed with the oral flukicides rafoxanide and triclabendazole and subsequent plasma Concentrations moni-tored. Peak plasma concentrations and areas under curves (AUC) of both chemicals were significantly reduced in the grazing compared with the housed lambs. In order to investigate the observation similar groups of lambs were dosed orally with chromium EDI'A and faecal throughput estimated. I t was observed that the rate of throughput was greater in the grazing lambs, leading to the conclusion that the differences in plasma concentrations of the flukicides was caused by a reduction in their absorption in the grazing lambs. The implications on flukicide efficacy and dose rates are discussed.     

Pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin in goats given enrofloxacin alone and in combination with probenecid.

The pharmacokinetics of enrofloxacin and its active metabolite ciprofloxacin were investigated in goats given enrofloxacin alone or in combination with probenecid. Enrofloxacin was administered i.m. at a dosage of 5 mg x kg(-1) alone or in conjunction with probenecid (40 mg x kg(-1), i.v.). Blood samples were drawn from the jugular vein at predetermined time intervals after drug injection. Plasma was separated and analysed simultaneously for enrofloxacin and ciprofloxacin by reverse-phase high performance liquid chromatography. The plasma concentration-time data for both enrofloxacin and ciprofloxacin were best described by a one-compartment open pharmacokinetic model. The elimination half-life (t(1/2beta)), area under the plasma concentration-time curve (AUC), volume of distribution (V(d(area))), mean residence time (MRT) and total systemic clearance (Cl(B)) were 1.39 h, 7.82 microg x h x mL, 1.52 L x kg(-1), 2.37 h and 802.9 mL x h(-1) x kg(-1), respectively. Enrofloxacin was metabolized to ciprofloxacin in goats and the ratio between the AUCs of ciprofloxacin and enrofloxacin was 0.34. The t(1/2beta), AUC and MRT of ciprofloxacin were 1.82 h, 2.55 microg x h x mL and 3.59 h, respectively. Following combined administration of probenecid and enrofloxacin in goats, the sum of concentrations of enrofloxacin and ciprofloxacin levels > or = 0.1 microg x mL(-1) persisted in plasma up to 12 h.Co-administration of probenecid did not affect the t(1/2beta), AUC, V(d (area)) and Cl(B) of enrofloxacin, whereas the values of t(1/2beta) (3.85 h), AUC (6.29 microg x h x mL), MRT (7.34 h) and metabolite ratio (0.86) of ciprofloxacin were significantly increased. The sum of both enrofloxacin and ciprofloxacin levels was > or = 0.1 microg x mL(-1) and was maintained in plasma up to 8 h in goats after i.m. administration of enrofloxacin alone. These data indicate that a 12 h dosing regime may be appropriate for use in goats.     

Pharmacokinetics of marbofloxacin after intravenous and intramuscular administration to ostriches

The pharmacokinetics of marbofloxacin was investigated after intravenous (IV) and intramuscular (IM) administration, both at a dose rate of 5 mg/kg BW, in six clinically healthy domestic ostriches. Plasma concentrations of marbofloxacin was determined by a HPLC/UV method. The high volume of distribution (3.22+/-0.98 L/kg) suggests good tissue penetration. Marbofloxacin presented a high clearance value (2.19+/-0.27 L/kgh), explaining the low AUC values (2.32+/-0.30 microgh/mL and 2.25+/-0.70 microgh/mL, after IV and IM administration, respectively) and a short half life and mean residence time (t(1/2 beta)=1.47+/-0.31 h and 1.96+/-0.35 h; MRT=1.46+/-0.02 h and 2.11+/-0.30 h, IV and IM, respectively). The absorption of marbofloxacin after IM administration was rapid and complete (C(max)=1.13+/-0.29 microg/mL; T(max)=0.36+/-0.071 h; MAT=0.66+/-0.22 h and F (%)=95.03+/-16.89).     

Pharmacokinetics of intramuscular ketamine in young ostriches premedicated with romifidine

Ketamine is a short-acting dissociative anaesthetic for chemical restraint and surgical anaesthesia in domestic and non-domestic animals. The present study was designed to determine the pharmacokinetics of a single dose of ketamine (10 mg/kg) after intramuscular (i.m.) administration to young ostriches premedicated with romifidine. Ketamine was rapidly absorbed after i.m. administration. Maximal ketamine concentration (C(max)) of 2.93 +/- 0.61 microg/ml was reached at 12.5 +/- 2.50 min and thereafter ketamine concentrations decreased rapidly. The elimination half-life (t(1/2 z)) obtained was 62.37 +/- 17.37 min and mean residence time (MRT) was 77.33 +/- 19.12 min. The area under the curve (AUC) was 114.19 +/- 15.76 microg x min/ml.     

Pharmacokinetics of diclofenac and its interaction with enrofloxacin in sheep

The pharmacokinetics of diclofenac was investigated in sheep given diclofenac alone (1mgkg(-1), i.v. or i.m.) and in combination with enrofloxacin (5mgkg(-1), i.v.). The plasma concentration-time data following i.v. administration of diclofenac was best described by a two compartment open pharmacokinetic model. The elimination half-life (t(1/2beta)), area under concentration-time-curve (AUC), volume of distribution (Vd(area)), mean residence time (MRT) and total body clearance (Cl(B)) were 1.03+/-0.18h, 12.17+/-1.98microg h ml(-1), 0.14+/-0.02Lkg(-1), 1.36+/-0.16h and 0.10+/-0.02Lkg(-1)h(-1), respectively. Following i.m. administration of diclofenac alone and in conjunction with enrofloxacin, the plasma concentration-time data best fitted to a one compartment open model. The t(1/2beta), AUC, Vd(area), MRT and Cl(B) were 1.33+/-0.10h, 7.32+/-1.01microg h mL(-1), 0.13+/-0.01Lkg(-1) and 0.07+/-0.01Lkg(-1)h(-1), respectively. Co-administration of enrofloxacin did not affect Vd(area) and MRT but absorption rate constant (K(a)), beta, t1/2Ka, t1/2beta, AUC, AUMC, Cl(B) and bioavailability (F) were significantly increased. This may be due to direct inhibition of cytochrome P(450) isozymes by enrofloxacin. A dose of 1.4mgkg(-1) of diclofenac administered every 6h may be appropriate for use in sheep.     

Influence of Escherichia coli endotoxin-induced fever on the pharmacokinetic behavior of marbofloxacin after intravenous administration in goats

The pharmacokinetic behavior of marbofloxacin was studied in seven healthy goats and in the same goats with induced fever after single-dose intravenous (i.v.) administration of 2 mg/kg b.w. Fever was induced by the administration of Escherichia coli endotoxin. Drug concentration in plasma was determined by high-performance liquid chromatography (HPLC). Drug distribution was somehow altered by fever as febrile goats showed a volume of distribution at steady-state (Vss = 0.72 +/- 0.15 L/kg) lower than normal goats (Vss = 1.19 +/- 0.33 L/kg). The elimination of the drug was also modified. Total plasma clearance (Cl) decreased from 0.24 +/- 0.12 L/kg/h in healthy animals to 0.13 +/- 0.05 L/kg/h in animals with endotoxin-induced fever, which is related to an increase in the area under the plasma concentration-time curve (AUC). Consequently, mean residence time (MRT) was also slightly increased in sick animals (MRT = 5.28 +/- 00.99 and 6.09 +/- 01.45 h, in healthy and febrile animals, respectively).     

Pharmacokinetic profiles of netobimin metabolites after oral administration of zwitterion and trisamine formulations of netobimin to cattle

Pharmacokinetic profiles of the major metabolites of netobimin were investigated in calves after oral administration of the compound (20 mg/kg) as a zwitterion suspension and trisamine salt solution in a two-way cross-over design. Blood samples were taken serially over a 72-h period and plasma was analysed by HPLC for netobimin (NTB) and its metabolites, including albendazole (ABZ), albendazole sulphoxide (ABZSO) and albendazole sulphone (ABZSO2). NTB was occasionally detected in plasma between 0.5 and 1.0 h post-treatment. ABZ was not detectable at any time. ABZSO was detected from 0.5-0.75 h up to 32 h post-administration, with a Cmax for the zwitterion suspension of 1.21 +/- 0.13 micrograms/ml and AUC of 18.55 +/- 1.45 micrograms.h/ml, respectively, which were significantly higher (P less than 0.01) than the Cmax (0.67 +/- 0.12 micrograms/ml) and AUC (8.57 +/- 0.91 micrograms.h/ml) for the trisamine solution. ABZSO2 was detected in plasma between 0.75 and 48 h post-administration. The zwitterion suspension resulted in a Cmax (2.91 +/- 0.10 micrograms/ml) and AUC (51.67 +/- 1.95 micrograms.h/ml) for ABZSO2, which were significantly higher (P less than 0.01) than those obtained for the trisamine solution (Cmax = 1.67 +/- 0.11 micrograms/ml and AUC = 22.77 +/- 1.09 micrograms.h/ml). The ratio of AUC for ABZSO2/ABZSO was 2.92 +/- 0.26 (zwitterion) and 2.80 +/- 0.20 (trisamine). The MRT for ABZSO2 was significantly longer (P less than 0.01) after treatment with the zwitterion suspension than after treatment with the trisamine solution.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma disposition and faecal excretion of oxfendazole, fenbendazole and albendazole following oral administration to donkeys

Fenbendazole (FBZ), oxfendazole (fenbendazole sulphoxide, FBZSO), and albendazole (ABZ) were administered orally to donkeys at 10mg/kg bodyweight. Blood and faecal samples were collected from 1 to 120 h post-treatment. The plasma and faecal samples were analysed by high performance liquid chromatography (HPLC). The parent molecule and its sulphoxide and sulphone (FBZSO(2)) metabolites did not reach detectable concentrations in any plasma samples following FBZ administration. ABZ was also not detected in any plasma samples, but its sulphoxide and sulphone metabolites were detected, demonstrating that ABZ was completely metabolised by first-pass mechanisms in donkeys. Maximum plasma concentrations (C(max)) of FBZSO (0.49microg/mL) and FBZSO(2) (0.60microg/mL) were detected at (t(max)) 5.67 and 8.00h, respectively, following administration of FBZSO. The area under the curve (AUC) of the sulphone metabolite (10.33microg h/mL) was significantly higher than that of the parent drug FBZSO (5.17microg h/mL). C(max) of albendazole sulphoxide (ABZSO) (0.08g/mL) and albendazole sulphone (ABZSO(2)) (0.04microg/mL) were obtained at 5.71 and 8.00h, respectively, following ABZ administration. The AUC of the sulphoxide metabolite (0.84microg h/mL) of ABZ was significantly higher than that of the sulphone metabolite (0.50microg h/mL). The highest dry-faecal concentrations of parent molecules were detected at 32, 34 and 30h for FBZSO, FBZ and ABZ, respectively. The sulphide metabolite was significantly higher than the parent molecule after FBZSO administration. The parent molecule was predominant in the faecal samples following FBZ administration. After ABZ administration, the parent molecule was significantly metabolised, probably by gastrointestinal microflora, to its sulphoxide metabolite (ABZSO) that showed a similar excretion profile to the parent molecule in the faecal samples. The AUC of the parent FBZ was significantly higher than that of FBZSO and ABZ in faeces. It is concluded that the plasma concentration of FBZSO was significantly higher than that of FBZ and ABZ. Although ABZ is not licensed for use in Equidae, its metabolites presented a greater plasma kinetic profile than FBZ which is licensed for use in horses. A higher metabolic capacity, first-pass effects and lower absorption of benzimidazoles in donkeys decrease bioavailability and efficacy compared to ruminants.     

Pharmacokinetics of enrofloxacin in lactating sheep

The pharmacokinetics of enrofloxacin (ENR) was investigated after its intravenous (iv) and intramuscular (im) administration in six healthy lactating sheep. After iv ENR injection (as a bolus), the elimination half-life (t(1/2beta)), the volume of distribution (Vd(area)), and the area under the concentration vs. time curve (AUC) were 3.30 (0.36)h, 2.91 (0.17)l/kg and 4.19 (0.18) microg h/ml, respectively. The maximum milk concentrations of ENR (C(max)), the area under the milk concentration vs. time curve (AUC(milk)) and the ratio AUC(milk)/AUC(serum) were 2.38 (0.14)microg/ml, 23.76 (2.21) microg h/ml and 5.62 (0.30), respectively. After im administration of ENR the t(1/2beta), C(max), time of C(max) (t(max)) and absolute bioavailability (F(abs)) were 3.87 (0.10)h, 0.74 (0.07) microg/ml, 0.83 (0.12)h and 75.35%, respectively. The C(max), AUC(milk) and the ratio AUC(milk)/AUC(serum) were 1.94 (0.13) microg/ml, 24.81 (2.25) microg h/ml and 8.15 (0.96), respectively.     

Disposition kinetics of moxifloxacin in lactating ewes

The present study was planned to investigate the plasma disposition kinetics and the pattern of moxifloxacin elimination in the milk of lactating ewes (n=6) following a single intravenous (IV) bolus or intramuscular (IM) injections at a dosage of 5 mg/kg in all animals. A crossover study was carried out in two phases separated by 21 days. Plasma and milk samples were collected serially for 72 h and moxifloxacin concentrations were assayed using high performance liquid chromatography with fluorescence detection. A two-compartment open model best described the decrease of moxifloxacin concentration in the plasma after IV injection. The disposition after IM administration moxifloxacin was best described by a one-compartment model. Following IV administration, the distribution half-life (t(1/2alpha)) was 0.22+/-0.02 h. The elimination half-life was 1.77+/-0.23 h. The volume of distribution at steady state (V(dss)) was 0.84+/-0.12L/kg, the total body clearance (Cl(tot)) was 0.34+/-0.04 L/h/kg and the area under the curve (AUC) was 14.74+/-2.16 microg h/mL. Following IM administration, the mean T(max), C(max), t(1/2el) and AUC values for plasma data were 1.45+/-0.02 h, 2.21+/-0.27 microg/mL, 2.68+/-0.19 h and 14.21+/-2.35 microg h/mL. The IM bioavailability was 96.35+/-17.23% and the in vitro protein binding of moxifloxacin ranged from 32-37%. Penetration of moxifloxacin from the blood into milk was rapid and extensive, and the moxifloxacin concentrations in milk exceeded those in plasma from 1h after administration. The kinetic values AUC(milk)/AUC(plasma) and C(maxmilk)/C(maxplasma) ratios indicated a wide penetration of moxifloxacin from the bloodstream to the mammary gland. The in vitro minimum inhibitory concentration (MIC) of moxifloxacin for Mannheimia haemolytica was found to be 0.035 microg/mL.     

Pharmacokinetics of enrofloxacin administered intravenously and orally to foals

OBJECTIVE: To determine the pharmacokinetics of enrofloxacin administered IV and orally to foals. ANIMALS: 5 clinically normal foals. PROCEDURE: A 2-dose cross-over trial with IV and oral administration was performed. Enrofloxacin was administered once IV (5 mg/kg of body weight) to 1-week-old foals, followed by 1 oral administration (10 mg/kg) after a 7-day washout period. Blood samples were collected for 48 hours after the single dose IV and oral administrations and analyzed for plasma enrofloxacin and ciprofloxacin concentrations by use of high-performance liquid chromatography. RESULTS: For IV administration, mean +/- SD total area under the curve (AUC0-infinity) was 48.54 +/- 10.46 microg x h/ml, clearance was 103.72 +/- 0.06 ml/kg/h, half-life (t1/2beta) was 17.10 +/- 0.09 hours, and apparent volume of distribution was 2.49 +/- 0.43 L/kg. For oral administration, AUC0-infinity was 58.47 +/- 16.37 microg x h/ml, t1/2beta was 18.39 +/- 0.06 hours, maximum concentration (Cmax) was 2.12 +/- 00.51 microg/ml, time to Cmax was 2.20 +/- 2.17 hours, mean absorption time was 2.09 +/- 0.51 hours, and bioavailability was 42 +/- 0.42%. CONCLUSIONS AND CLINICAL RELEVANCE: Compared with adult horses given 5 mg of enrofloxacin/kg IV, foals have higher AUC0-infinity, longer t1/2beta, and lower clearance. Concentration of ciprofloxacin was negligible. Using a target Cmax to minimum inhibitory concentration ratio of 1:8 to 1:10, computer modeling suggests that 2.5 to 10 mg of enrofloxacin/kg administered every 24 hours would be effective in foals, depending on minimum inhibitory concentration of the pathogen.     

Bioavailability of albendazole sulphoxide after netobimin administration in sheep: effects of fenbendazole coadministration.

After oral co-administration of two dosages of netobimin (7.5 and 20 mg kg-1 with fenbendazole (1.1 mg kg-1) to Merino sheep, the AUC0-infinity of albendazole sulphoxide at the lower dosage of netobimin, was significantly increased (75.5 per cent) from control value (34.43 +/- 7.91 versus 60.33 +/- 11.93 microg h ml-1). The pharmacokinetic parameters MRT and T1/2 were also increased: 18.96 +/- 2.54 vs 26.44 +/- 4.69 h and 10.31 +/- 1.72 vs 22.28 +/- 6.75 h respectively. No data corresponding to the higher dosage of netobimin (20 mg kg-1) were statistically different from control values. It is concluded that fenbendazole increases the bioavailability of albendazole sulphoxide in sheep at the 7.5 mg kg-1 dosage, and this may produce a potentiated anthelmintic action.     

Pharmacokinetic study of rhizoma Curcumae oil and rhizoma Curcumae oil-β-cyclodextrin inclusion complex in pigs after oral administration

Pharmacokinetics of rhizoma Curcumae oil-pure drug (RCO-PD) and its β-cyclodextrin inclusion complex (RCO-βCD) were studied in a randomized two-way crossover design following a single oral administration of the two formulations. Germacrone concentrations in plasma were determined by high-performance liquid chromatography with UV detector. The concentrations vs. time data were analyzed by a noncompartmental pharmacokinetic method. The result showed that germacrone in both groups was rapidly absorbed followed by a slow elimination. The main parameters in RCO-PD group were as follows: t(1/2λz) 6.63±1.08 h, C(max) 2.50±0.34 μg/mL, MRT 7.19±0.93 h, and AUC(0-∞) 13.92±2.75 mg/L·h, while in RCO-βCD group, t(1/2λz) 6.77 ± 0.67 h, C(max) 2.98±0.24 μg/mL, MRT 8.87±0.76 h, and AUC(0-∞) 21.60 ± 1.95 mg/L·h, respectively. The above results indicated that C(max), T(max), AUC(0-t), AUC(0-∞), and MRT in RCO-βCD group were significantly different from RCO-PD group, and the relative bioavailability of RCO-βCD group is significantly higher while compared to RCO-PD group (F=156%, with its 90% confidence interval of 145-169%).