Fexofenadine in horses: pharmacokinetics, pharmacodynamics and effect of ivermectin pretreatment

The pharmacokinetics and the effects on inhibition of histamine-induced cutaneous wheal formation of the histamine H1-antagonist fexofenadine were studied in horse. The effect of ivermectin pretreatment on the pharmacokinetics of fexofenadine was also examined. After intravenous infusion of fexofenadine at 0.7 mg/kg bw the mean terminal half-life was 2.4 h (range: 2.0-2.7 h), the apparent volume of distribution 0.8 L/kg (0.5-0.9 L/kg), and the total body clearance 0.8 L/h/kg (0.6-1.2 L/h/kg). After oral administration of fexofenadine at 10 mg/kg bw bioavailability was 2.6% (1.9-2.9%). Ivermectin pretreatment (0.2 mg/kg, p.o.) 12 h before oral fexofenadine decreased the bioavailability to 1.5% (1.4-2.1%). In addition, the area under the plasma concentration-time curve decreased 27%. Ivermectin did not affect the pharmacokinetics of i.v. administered fexofenadine. Ivermectin may influence fexofenadine absorption by interfering in intestinal efflux and influx pumps, such as P-glycoprotein and the organic anion transport polypeptide family. Oral and i.v. fexofenadine significantly decreased histamine-induced wheal formation, with a maximal duration of 6 h. A pharmacokinetic/pharmacodynamic link model indicated that fexofenadine in horse has antihistaminic effects at low plasma concentrations (EC50 = 16 ng/mL). However, oral treatments of horses with fexofenadine may not be suitable due to the low bioavailability.     

Pharmacokinetics and tissue fluid distribution of cephalexin in the horse after oral and i.v. administration

The purpose of this study was to determine the pharmacokinetics and tissue fluid distribution of cephalexin in the adult horse following oral and i.v. administration. Cephalexin hydrate (10 mg/kg) was administered to horses i.v. and plasma samples were collected. Following a washout period, cephalexin (30 mg/kg) was administered intragastrically. Plasma, interstitial fluid (ISF) aqueous humor, and urine samples were collected. All samples were analyzed by high-pressure liquid chromatography (HPLC). Following i.v. administration, cephalexin had a plasma half-life (t(1/2)) of 2.02 h and volume of distribution [V(d(ss))] of 0.25 L/kg. Following oral administration, the average maximum plasma concentration (C(max)) was 3.47 mug/mL and an apparent half-life (t(1/2)) of 1.64 h. Bioavailability was approximately 5.0%. The AUC(ISF):AUC(plasma) ratio was 80.55% which corresponded to the percentage protein-unbound drug in the plasma (77.07%). The t(1/2) in the ISF was 2.49 h. Cephalexin was not detected in the aqueous humor. The octanol:water partition coefficient was 0.076 +/- 0.025. Cephalexin was concentrated in the urine with an average concentration of 47.59 microg/mL. No adverse events were noted during this study. This study showed that cephalexin at a dose of 30 mg/kg administered orally at 8 h dosage intervals in horses can produce plasma and interstitial fluid drug concentrations that are in a range recommended to treat susceptible gram-positive bacteria (MIC < or = 0.5 microg/mL). Because of the low oral bioavailability of cephalexin in the horse, the effect of chronic dosing on the normal intestinal bacterial flora requires further investigation.     

Cetirizine in horses: pharmacokinetics and pharmacodynamics following repeated oral administration

The pharmacokinetics of the histamine H(1)-antagonist cetirizine and its effect on histamine-induced cutaneous wheal formation were studied in six healthy horses following repeated oral administration. After three consecutive administrations of cetirizine (0.2 mg/kg body weight, bw) every 12h, the trough plasma concentration of cetirizine was 16+/-4 ng/mL (mean+/-SD) and the wheal formation was inhibited by 45+/-23%. After four additional administrations of cetirizine (0.4 mg/kg bw) every 12 h, the trough plasma concentration was 48+/-15 ng/mL and the wheal formation was inhibited by 68+/-11%. The terminal half-life was about 5.8 h. A pharmacokinetic/pharmacodynamic link model showed that the maximal inhibition of wheal formation was about 95% and the EC(50) about 18 ng/mL. It is concluded that cetirizine in doses of 0.2-0.4 mg/kg bw administered at 12 h intervals exhibits favourable pharmacokinetic and pharmacodynamic properties without causing visible side effects, and the drug may therefore be a useful antihistamine in equine medicine.     

Disposition of flunixin meglumine injectable preparation administered orally to healthy horses

An injectable preparation of flunixin meglumine was administered orally and intravenously at a dose of 1.1 mg/kg to six healthy adult horses in a cross-over design. Flunixin meglumine was detected in plasma within 15 min of administration and peak plasma concentrations were observed 45-60 min after oral administration. Mean bioavailability of the oral drug was 71.9 +/- 26.0%, with an absorption half-life of 0.76 h. The apparent elimination half-life after oral administration was 2.4 h. The injectable preparation of flunixin meglumine is suitable for oral administration to horses.     

Pharmacokinetics of voriconazole after oral and intravenous administration to horses

OBJECTIVE: To characterize pharmacokinetics of voriconazole in horses after oral and IV administration and determine the in vitro physicochemical characteristics of the drug that may affect oral absorption and tissue distribution. ANIMALS: 6 adult horses. PROCEDURES: Horses were administered voriconazole (1 mg/kg, IV, or 4 mg/kg, PO), and plasma concentrations were measured by use of high-performance liquid chromatography. In vitro plasma protein binding and the octanol:water partition coefficient were also assessed. RESULTS: Voriconazole was adequately absorbed after oral administration in horses, with a systemic bioavailability of 135.75 +/- 18.41%. The elimination half-life after a single orally administered dose was 13.11 +/- 2.85 hours, and the maximum plasma concentration was 2.43 +/- 0.4 microg/mL. Plasma protein binding was 31.68%, and the octanol:water partition coefficient was 64.69. No adverse reactions were detected during the study. CONCLUSIONS AND CLINICAL RELEVANCE: Voriconazole has excellent absorption after oral administration and a long half-life in horses. On the basis of the results of this study, it was concluded that administration of voriconazole at a dosage of 4 mg/kg, PO, every 24 hours will attain plasma concentrations adequate for treatment of horses with fungal infections for which the fungi have a minimum inhibitory concentration 相似文献   

Antimicrobial disposition in pulmonary epithelial lining fluid of horses, part II. Doxycycline

Doxycycline concentrations, following two types of oral administration to horses, in pulmonary epithelial lining fluid (PELF) were examined and compared to plasma concentrations. The oral bioavailability was estimated from plasma concentrations achieved after an intravenous study in two horses. Doxycycline (10 mg/kg) was administered either intragastric or as topdressing to nonfasted horses. Blood samples were collected for drug analysis, before and 11 times after administration during 24 h. PELF samples were collected by a tampon device four times after drug administration and analysed for doxycycline concentrations. Another two horses received doxycycline intravenously at a dose of 3 mg/kg and plasma was taken 14 times during a 24- h period. The oral bioavailability of doxycycline was calculated to 17% after intragastric administration and 6% after topdressing administration in nonfasted horses. The degree of penetration of doxycycline into PELF, as described by AUC(PELF) /AUC(plasma) ratios, was 0.87 after intragastric administration. The results indicate that clinically relevant doxycycline concentrations are possible to maintain in PELF after intragastric administration. Furthermore, if bioavailability could be enhanced for per os administration, doxycycline might be a valuable drug for the treatment of lower airway infections in horses.     

Pharmacokinetics of tinidazole in the horse

Serum tinidazole concentrations were monitored in five clinically healthy adult horses after intravenous (i.v.) and oral administration of the drug (15 mg/kg and 25 mg/kg, respectively). After i.v. administration, the mean residence time was 7.0 h, the elimination half-life 5.2 h and the body clearance rate 1.6 ml/min/kg. The distribution volume was found to be 660 ml/kg. After oral administration, the mean residence time was 8.5 h, the absorption half-life 1.1 h and the bioavailability essentially 100%. In view of the in-vitro sensitivities of various anaerobic bacteria, a dosage of 10-15 mg/kg of tinidazole, orally, at 12-h intervals, can be recommended for the treatment of anaerobic infections in horses.     

The comparative plasma pharmacokinetics of intravenous cefpodoxime sodium and oral cefpodoxime proxetil in beagle dogs

The pharmacokinetic properties of cefpodoxime, and its prodrug, cefpodoxime proxetil, were evaluated in two separate studies, one following intravenous (i.v.) administration of cefpodoxime sodium and the second after oral (p.o.) administration of cefpodoxime proxetil to healthy dogs. After cefpodoxime administration, serial blood samples were collected and plasma concentrations were determined by high performance liquid chromatography (HPLC). A single i.v. administration of cefpodoxime sodium at a dose of 10 mg cefpodoxime/kg body weight resulted in a cefpodoxime average maximum plasma concentration (Cmax) of 91 (+/-17.7) microg/mL, measured at 0.5 h after drug administration, an average half-life (t1/2) of 4.67 (+/-0.680) h, an average AUC(0-infinity) of 454 (+/-83.1) h.microg/mL, an average V(d(ss)) of 151 (+/-27) mL/kg, an average Cl(B) of 22.7 (+/-4.2) mL/h/kg and an average MRT(0-infinity) of 5.97 (+/-0.573) h. When dose normalized to 10 mg cefpodoxime/kg body weight, cefpodoxime proxetil administered orally resulted in Cmax of 17.8 +/- 11.4 microg/mL for the tablet formulation and 20.1 +/- 6.20 microg/mL for the suspension formulation and an average AUC(0-LOQ) of 156 (+/-76.1) h.microg/mL for the tablet formulation and 162 (+/-48.6) h.microg/mL for the suspension formulation. Relative bioavailability of the two oral formulations was 1.04 (suspension compared with tablet), whereas the absolute bioavailability of both oral formulations was estimated to be approximately 35-36% in the cross-study comparison with the i.v. pharmacokinetics. Combined with previous studies, these results suggest that a single daily oral dose of 5-10 mg cefpodoxime/kg body weight as cefpodoxime proxetil maintains plasma concentrations effective for treatment of specified skin infections in dogs.     

Pharmacokinetic profile and in vitro selective cyclooxygenase-2 inhibition by nimesulide in the dog

The pharmacokinetic properties and in vitro potency of nimesulide, a nonsteroidal anti-inflammatory drug (NSAID) were investigated in 8 or 10 dogs after intravenous (i.v.), intramuscular (i.m.) and oral (single and multiple dose) administrations at the nominal dose of 5 mg/kg. After i.v. administration, the plasma clearance was 15.3 +/- 4.2 mL/kg/h, the steady-state volume of distribution was low (0.18 +/- 0.011 L/kg) and the elimination half-life was 8.5 +/- 2.1 h. After i.m. administration, the terminal half-life was 14.0 +/- 5.3 h indicating a slow process of absorption with a maximum plasma concentration (6.1 +/- 1.5 microg/mL) at 10.9 +/- 2.1 h postadministration and the systemic bioavailability was 69 +/- 22%. After oral administration in fasted dogs, the maximal plasma concentration (10.1 +/- 2.7 microg/mL) was observed 6.1 +/- 1.6 h after drug administration, the plasma half-life was 6.2 +/- 1.9 h and the mean bioavailability was 47 +/- 12%. After daily oral administrations for 5 days, the average plasma concentration during the fifth dosage interval was 8.1 +/- 2.9 microg/mL and the overall bioavailability was 58 +/- 16%. The mean accumulation ratio was 1.27 +/- 0.4. In vitro nimesulide inhibitory potencies for cyclooxygenase (COX)-1 and COX-2 isoenzymes were determined using a whole blood assay. Canine clotting blood was used to test for inhibition of COX-1 activity and whole blood stimulated by lipopolysaccharide (LPS) was used to test for inhibition of COX-2 activity. The inhibitory concentration (IC50) for inhibition of COX-2 and COX-1 were 1.6 +/- 0.4 microM (0.49 +/- 0.12 microg/mL) and 20.3 +/- 2.8 microM (6.3 +/- 0.86 microg/mL) giving a nimesulide COX-1/COX-2 ratio of 12.99 +/- 3.41. It was concluded that at the currently recommended dosage regimen (5 mg/kg), the plasma concentration totally inhibits COX-2 and partly inhibits COX-1 isoenzyme.     

Bioavailability of oral penicillins in the horse: a comparison of pivampicillin and amoxicillin

The pharmacokinetics of ampicillin and amoxicillin following intravenous administration at a dose rate of 15 and 10 mg/kg respectively were studied in four healthy adult horses. Pharmacokinetics of pivampicillin and amoxicillin were studied after oral administration to four healthy adult horses. Pivampicillin, a prodrug of ampicillin, was administered orally to starved and fed horses at a dose rate of 19.9 mg/kg, which is equivalent on a molecular basis to 15 mg/kg ampicillin. Amoxicillin was administered orally to starved horses only, at a dose rate of 20 mg/kg. Ampicillin and amoxicillin concentrations in plasma, synovial fluid and urine were determined. Mean biological half-life of intravenously administered ampicillin and amoxicillin was 1.72 and 1.43 h respectively, whilst the distribution volume (Vss) appeared to be 0.180 and 0.192 1/kg. Orally administered pivampicillin and amoxicillin were rapidly absorbed. A maximum concentration in plasma of 3.80 micrograms/ml was reached 2 h after administration of pivampicillin to starved horses; in fed horses a maximum concentration of 5.12 micrograms/ml was reached 1 h after administration. After oral administration of amoxicillin a maximum concentration of 2.03 micrograms/ml was reached after 1 h. The (absolute) bioavailability of pivampicillin administered orally was 30.9% in starved horses and 35.9% in fed horses. The bioavailability of amoxicillin administered orally was 5.3% in starved horses.     

Hydroxyzine and cetirizine pharmacokinetics and pharmacodynamics after oral and intravenous administration of hydroxyzine to healthy dogs

Pharmacokinetic parameters of hydroxyzine and its active metabolite cetirizine were determined after oral and intravenous administration of 2 mg kg(-1) of hydroxyzine to six healthy dogs. Plasma drug levels were determined with high-pressure liquid chromatography. Pharmacodynamic studies evaluated the suppressive effect on histamine and anticanine IgE-mediated cutaneous wheal formation. Pharmacokinetic and pharmacodynamic correlations were determined with computer modelling. The mean systemic availability of oral hydroxyzine was 72%. Hydroxyzine was rapidly converted to cetirizine regardless of the route of administration. The mean area-under-the-curve was eight and ten times higher for cetirizine than hydroxyzine after intravenous and oral dosing, respectively. After oral administration of hydroxyzine, the mean peak concentration of cetirizine was approximately 2.2 microg mL(-1) and that of hydroxyzine 0.16 microg mL(-1). The terminal half-life for cetirizine varied between 10 and 11 h after intravenous and oral administration of hydroxyzine. A sigmoidal relationship was fit to the data comparing cetirizine plasma concentration to wheal suppression. Maximum inhibition (82% and 69% for histamine and anticanine IgE-mediated skin reactions, respectively) was observed during the first 8 h, which correlated with a plasma concentration of cetirizine greater than 1.5 microg mL(-1). Pharmacological modelling suggested that increasing either hydroxyzine dosages or frequencies of administration would not result in histamine inhibition superior to that obtained with twice daily hydroxyzine at 2 mg kg(-1). In conclusion, there was rapid conversion of hydroxyzine to cetirizine. The reduction of wheal formation appeared almost entirely due to cetirizine. Pharmacodynamic modelling predicted that maximal antihistamine effect would occur with twice daily oral administration of hydroxyzine at 2 mg kg(-1).     

Clinical pharmacology of clemastine in healthy dogs

The pharmacokinetic properties of clemastine were investigated in six healthy dogs and compared with the effect of the drug recorded as inhibition of wheal formation induced by intradermal injections of histamine. Clemastine clearance was high (median: 2.1 L h(-1) kg(-1)) and the volume of distribution large (13.4 L kg(-1)). The half-life after intravenous administration was 3.8 h and the plasma protein binding level in vitro was 98%. After oral administration, the bioavailability was only 3%. Given intravenously, clemastine (0.1 mg kg(-1)) inhibited wheal formation completely for 7 h, whereas the effect after oral administration (0.5 mg kg(-1)) was minor. The data show that most dosage regimens suggested in the literature for the oral administration of clemastine to dogs are likely to give too low a systemic exposure of the drug to allow effective therapy.     

Pharmacokinetics of meloxicam in plasma and urine of horses

OBJECTIVE: To determine pharmacokinetic parameters for meloxicam, a nonsteroidal anti-inflammatory drug, in horses. ANIMALS: 8 healthy horses. PROCEDURE: In the first phase of the study, horses were administered meloxicam once in accordance with a 2 x 2 crossover design (IV or PO drug administration; horses fed or not fed). The second phase used a multiple-dose regimen (daily oral administration of meloxicam for 14 days), with meloxicam administered at the recommended dosage (0.6 mg/kg). Plasma and urine concentrations of meloxicam were measured by use of validated methods with a limit of quantification of 10 ng/mL for plasma and 20 ng/mL for urine. RESULTS: Plasma clearance was low (mean +/- SD; 34 +/- 0.5 mL/kg/h), steady-state volume of distribution was limited (0.12 +/- 0.018 L/kg), and terminal half-life was 8.54 +/- 3.02 hours. After oral administration, bioavailability was nearly total regardless of feeding status (98 +/- 12% in fed horses and 85 +/- 19% in nonfed horses). During once-daily administration for 14 days, we did not detect drug accumulation in the plasma. Meloxicam was eliminated via the urine with a urine-to-plasma concentration that ranged from 13 to 18. Concentrations were detected for a relatively short period (3 days) after administration of the final daily dose. CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study support once-daily administration of meloxicam regardless of the feeding status of a horse and suggest a period of at least 3 days before urine concentrations of meloxicam reach concentrations that could be used in drug control programs.     

Pharmacokinetics and oral bioavailability of pentoxyfylline in broiler chickens

The pharmacokinetic properties of pentoxyfylline and its metabolites were determined in healthy chickens after single intravenous and oral dosage of 100 mg/kg pentoxyfylline. Plasma concentrations of pentoxyfylline and its metabolites were determined by a validated high-performance liquid chromatographic method. After intravenous (i.v.) and oral (p.o.) administration, the plasma concentration-time curves were best described by a one-compartment open model. The mean elimination half-life (t(1/2el)) of pentoxyfylline was 1.05 h, total body clearance 1.90 L/h x kg, volume of distribution 2.40 L/kg and the mean residence time was 2.73 h, after i.v. administration. After oral dosing, mean maximal plasma concentration of pentoxyfylline was 4.01 microg/mL and the interval from p.o. administration until maximum concentration was 1.15 h. The mean oral bioavailability was found to be 28.2%. Metabolites I, IV and V were present in chicken plasma after both i.v. and p.o. administration, with metabolite V being the most dominant.     

Disposition, elimination, and bioavailability of phenytoin and its major metabolite in horses

OBJECTIVE: To determine pharmacokinetics and excretion of phenytoin in horses. ANIMALS: 6 adult horses. PROCEDURE: Using a crossover design, phenytoin was administered (8.8 mg/kg of body weight, IV and PO) to 6 horses to determine bioavailability (F). Phenytoin also was administered orally twice daily for 5 days to those same 6 horses to determine steady-state concentrations and excretion patterns. Blood and urine samples were collected for analysis. RESULTS: Mean (+/- SD) elimination half-life following a single IV or PO administration was 12.6+/-2.8 and 13.9+/-6.3 hours, respectively, and was 11.2+/-4.0 hours following twice-daily administration for 5 days. Values for F ranged from 14.5 to 84.7%. Mean peak plasma concentration (Cmax) following single oral administration was 1.8+/-0.68 microg/ml. Steady-state plasma concentrations following twice-daily administration for 5 days was 4.0+/-1.8 microg/ml. Of the 12.0+/-5.4% of the drug excreted during the 36-hour collection period, 0.78+/-0.39% was the parent drug phenytoin, and 11.2+/-5.3% was 5-(phydroxyphenyl)-5-phenylhydantoin (p-HPPH). Following twice-daily administration for 5 days, phenytoin was quantified in plasma and urine for up to 72 and 96 hours, respectively, and p-HPPH was quantified in urine for up to 144 hours after administration. This excretion pattern was not consistent in all horses. CONCLUSIONS AND CLINICAL RELEVANCE: Variability in F, terminal elimination-phase half-life, and Cmax following single or multiple oral administration of phenytoin was considerable. This variability makes it difficult to predict plasma concentrations in horses after phenytoin administration.     

The pharmacokinetics of meclofenamic acid in the horse

The pharmacokinetics of meclofenamic acid were studied in Thoroughbred horses and in ponies. After intravenous (i.v.) administration of either 2 mg/kg or 4 mg/kg sodium meclofenamate the elimination half-life was of the order of 0.9 h while the volume of distribution was found to be 0.128 litre/kg. Elimination was in accordance with a one-compartment model. Following oral administration of either meclofenamic acid (4 mg/kg) or sodium meclofenamate (4 mg/kg) a much longer terminal half-life than that calculated for K _el from i.v. data was found. This anomaly indicated that the 'flip-flop' phenomenon was present, i.e. K _a exceeded K _el. More rapid and higher peak levels occurred following sodium meclofenamate than meclofenamic acid, although total bioavailability was similar. Studies in ponies with meclofenamic acid showed a lower absorption than that found in Thoroughbreds. Overnight fasting before meclofenamic acid administration did not alter the rate or extent of absorption. Intramuscular administration of sodium meclofenamate resulted in low plasma concentrations and after 25 h only 46% of the drug had been absorbed.     

Evaluation of the pharmacokinetics and bioavailability of intravenously and orally administered amiodarone in horses

OBJECTIVE: To determine the clinical effects and pharmacokinetics of amiodarone after single doses of 5 mg/kg administered orally or intravenously. ANIMALS: 6 healthy adult horses. PROCEDURE: In a cross over study, clinical signs and electrocardiographic variables were monitored and plasma and urine samples were collected. A liquid chromatography-mass spectrometry method was used to determine the percentage of protein binding and to measure plasma and urine concentrations of amiodarone and the active metabolite desethylamiodarone. RESULTS: No adverse clinical signs were observed. After IV administration, median terminal elimination half-lives of amiodarone and desethylamiodarone were 51.1 and 75.3 hours, respectively. Clearance was 0.35 L/kg x h, and the apparent volume of distribution for amiodarone was 31.1 L/kg. The peak plasma desethylamiodarone concentration of 0.08 microg/mL was attained 2.7 hours after IV administration. Neither parent drug nor metabolite was detected in urine, and protein binding of amiodarone was 96%. After oral administration of amiodarone, absorption of amiodarone was slow and variable; bioavailability ranged from 6.0% to 33.7%. The peak plasma amiodarone concentration of 0.14 microg/mL was attained 7.0 hours after oral administration and the peak plasma desethylamiodarone concentration of 0.03 microg/mL was attained 8.0 hours after administration. Median elimination half-lives of amiodarone and desethylamiodarone were 24.1 and 58.6 hours, respectively. CONCLUSION AND CLINICAL RELEVANCE: Results indicate that the pharmacokinetic distribution of amiodarone is multicompartmental. This information is useful for determining treatment regimens for horses with arrythmias. Amiodarone has low bioavailability after oral administration, does not undergo renal excretion, and is highly protein-bound in horses.     

Pharmacokinetics and bioavailability of doxycycline in fasted and nonfasted broiler chickens

The pharmacokinetics and the influence of food on the kinetic profile and bioavailability of doxycycline was studied after a single intravenous (i.v.) and oral dose of 10.0 mg/kg body weight in 7-week-old broiler chickens. Following i.v. administration the drug was rapidly distributed in the body with a distribution half-life of 0.21 +/- 0.01 h. The elimination half-life of 6.78 +/- 0.06 h was relatively long and resulted from both a low total body clearance of 0.139 +/- 0.007 L/h.kg and a large volume of distribution of 1.36 +/- 0.06 L/kg. After oral administration to fasted chickens, the absorption of doxycycline was quite fast and substantial as shown by the absorption half-life of 0.39 +/- 0.03 h, the maximal plasma concentration of 4.47 +/- 0.16 micrograms/mL and the time to reach the Cmax of 1.73 +/- 0.06 h. The distribution and the final elimination of the drug were slower than after i.v. administration. The absolute bioavailability was 73.4 +/- 2.5%. The presence of food in the intestinal tract reduced and extended the absorption (t1/2a = 1.23 +/- 0.21 h; Cmax = 3.07 +/- 0.23 micrograms/mL; tmax = 3.34 +/- 0.21 h). The absolute bioavailability was reduced to 61.1% +/- 4.4%.     

Pharmacokinetics and therapeutic efficacy of rimantadine in horses experimentally infected with influenza virus A2.

OBJECTIVE: To determine pharmacokinetics of single and multiple doses of rimantadine hydrochloride in horses and to evaluate prophylactic efficacy of rimantadine in influenza virus-infected horses. ANIMALS: 5 clinically normal horses and 8 horses seronegative to influenza A. PROCEDURE: Horses were given rimantadine (7 mg/kg of body weight, i.v., once; 15 mg/kg, p.o., once; 30 mg/kg, p.o., once; and 30 mg/kg, p.o., q 12 h for 4 days) to determine disposition kinetics. Efficacy in induced infections was determined in horses seronegative to influenza virus A2. Rimantadine was administered (30 mg/kg, p.o., q 12 h for 7 days) beginning 12 hours before challenge-exposure to the virus. RESULTS: Estimated mean peak plasma concentration of rimantadine after i.v. administration was 2.0 micrograms/ml, volume of distribution (mean +/- SD) at steady-state (Vdss) was 7.1 +/- 1.7 L/kg, plasma clearance after i.v. administration was 51 +/- 7 ml/min/kg, and beta-phase half-life was 2.0 +/- 0.4 hours. Oral administration of 15 mg of rimantadine/kg yielded peak plasma concentrations of < 50 ng/ml after 3 hours; a single oral administration of 30 mg/kg yielded mean peak plasma concentrations of 500 ng/ml with mean bioavailability (F) of 25%, beta-phase half-life of 2.2 +/- 0.3 hours, and clearance of 340 +/- 255 ml/min/kg. Multiple doses of rimantadine provided steady-state concentrations in plasma with peak and trough concentrations (mean +/- SEM) of 811 +/- 97 and 161 +/- 12 ng/ml, respectively. Rimantadine used prophylactically for induced influenza virus A2 infection was associated with significant decreases in rectal temperature and lung sounds. CONCLUSIONS AND CLINICAL RELEVANCE: Oral administration of rimantadine to horses can safely ameliorate clinical signs of influenza virus infection.     

Pharmacokinetics of ofloxacin in broiler chicken

Pharmacokinetics of ofloxacin, a fluoroquinolone antimicrobial agent, was determined in broiler chickens after intravenous or oral administration of a single dose (10 mg/kg). Ofloxacin concentrations in plasma were determined using a high-performance liquid chromatography assay. Plasma concentration profiles were analyzed by the noncompartmental method. Elimination half-life and mean residence time of ofloxacin in plasma were 4.46 and 5.48 h after intravenous administration and 5.85 and 7.43 h, respectively, after oral administration. Maximal plasma concentration of 3.65 microg/mL was achieved at 1.25 h after oral administration. Apparent volume of distribution of 1.76 and 2.16 L/kg and total body clearance of 4.96 and 4.5 mL/min/kg were obtained following intravenous and oral administration, respectively. The oral bioavailability of ofloxacin was 110.01%. Ofloxacin was found to be more rapidly absorbed, widely distributed and more quickly eliminated than other fluoroquinolones in broilers. Based on these kinetic parameters, a dosage of 10 mg/kg given orally every 24 h can be recommended for the treatment of bacterial infections with MIC90 < 0.3 microg/mL.