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.     

Flumequine in the Goat: Pharmacokinetics after Intravenous and Intramuscular Administration

The pharmacokinetics of flumequine, administered intravenously and intramuscularly at a single dose of 20 mg/kg, was investigated in healthy goats. After intravenous injection, flumequine distributed rapidly (t1/2alpha = 0.87+/-0.15 h) but was eliminated slowly (t1/2beta = 7.12+/-1.27 h); mean clearance (Cl) and volume of distribution (Vdss) were 0.32+/-0.03 (L/(h x kg) and 1.22+/-029 (L/kg), respectively. After intramuscular administration, the peakserum concentration (Cmax = 7.40+/-0.5 microg/ml) was reached in about 1.5 h (Tmax) and bioavailability was about 93%. Estimated flumequine serum levels following repeated intramuscular administration of the aqueous suspension used in the study (7.23+/-0.7 microg/ml and 4.82+/-0.47 microg/ml at intervals of 8 and 12 h, respectively) indicated that to maintain serum levels above MIC values for susceptible bacteria a dosage regimen of 20 mg/kg every 12 h is necessary by the intramuscular route.     

Pharmacokinetic and depletion studies of sarafloxacin after oral administration to eel (Anguilla anguilla).

The pharmacokinetics of sarafloxacin applied by oral gavage at a dose of 15 mg/kg b.w. was studied in eel (Anguilla anguilla) at water temperature of 24 degrees C. Sarafloxacin levels were determined using high performance liquid chromatography with a quantitation limit of 0.07 microg/ml or gram. The time to peak plasma concentration, Tmax, was 12 hr and peak concentration, Cmax, was 2.64 microg/ml. The absorption rate constant (k(a)) was 0.23 hr(-1) (r=0.996). The drug disposition curve after Tmax was fitted to a two-compartment open model. The distribution rate constant (alpha) was 0.085 hr(-1) (r=0.972), and the half-life (t(1,2alpha)) was 8.15 hr. The elimination rate constant (beta) was 0.023 hr(-1) (r=0.909), and the half-life (t(1/2beta)) was 30.13 hr. The estimated area under the curve, AUC, was 56.7 microg.hr/ml. The peak concentrations of drug in liver, kidney, muscle, and skin were 13.39 (12 hr), 5.53 (12 hr), 1.82 (24 hr), and 0.78 microg/g (40 hr), respectively. The time for sarafloxacin mean levels to fall below detectable limits in the plasma, muscle, and skin were 7 days but for the liver and kidney were 14 days.     

The steady-state pharmacokinetics and bioequivalence of carprofen administered orally and subcutaneously in dogs

Eighteen male Beagle dogs were randomized to oral (p.o.) or subcutaneous (s.c.) carprofen administration in a two-sequence, two-period crossover design with a 10-day washout between periods. Twenty-five milligrams of carprofen was administered p.o. or s.c. every 12 h for 7 days. Plasma concentrations of carprofen collected after the first and last treatments were determined by high-performance liquid chromatography. Carprofen concentration data were natural log transformed and geometric means were calculated for maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC0--12) following the first dose and Cmax and AUC0--12 following administration of the last dose. Formulations were considered bioequivalent if the 90% confidence interval (CI) of the mean difference for each variable between formulations were within -20% and 25% of the oral formulation. The mean Cmax and AUC0--12 were 16.9 microg/mL and 73.1 microg. h/mL, respectively, following a single oral dose and 8.0 microg/mL and 64.3 microg x h/mL, respectively, following a single s.c. injection. The 90% CI for Cmax (-56.8 to -48.7%) was outside of the bioequivalence criteria whereas the 90% CI for AUC0--12 (-16.3 to -7.5%) was within the bioequivalence criteria. At steady-state, the mean Cmax and AUC0--12 were 18.7 microg/mL and 101.9 microg x h/mL, respectively, following p.o. administration and 14.7 microg/mL and 111.0 microg x h/mL, respectively, following s.c. injection. The 90% CI was outside the bioequivalence criteria for Cmax (-30.8 to -10.8) but within the bioequivalence criteria for AUC0--12 (2.3-15.9%). The results of this study indicate that peak plasma concentrations of carprofen differ when administered p.o. and s.c., but that total drug exposure following a single dose and at steady-state are bioequivalent.     

Pharmacokinetics of sulfadimethoxine and ormetoprim in a 5:1 ratio following intraperitoneal and oral administration, in the hybrid striped bass (Morone chrysops x Morone saxitalis)

Selected pharmacokinetic parameters for sulfadimethoxine and ormetoprim, administered in a 5:1 ratio, via the oral and intraperitoneal (i.p.) routes were determined in the hybrid striped bass (Morone chrysops x Morone saxitalis). Plasma concentrations of both drugs were determined by high-performance liquid chromatography. A first-order one-compartment model adequately described plasma drug disposition. The elimination half-lives for sulfadimethoxine following i.p. and oral administration were 26 and 10.5 h, respectively. The half-lives for ormetoprim administered via i.p. and oral routes were 7.5 and 3.9 h, respectively. Cmax for sulfadimethoxine via the i.p. and oral routes were calculated to be 27.7 (+/-9.0) microg/mL at 3.6 h and 3.2 (+/-1.2) microg/mL at 1.2 h, respectively. Cmax for ormetoprim via the i.p. route was calculated to be 1.2 (+/-0.5) microg/mL at 9.1 h and 1.58 (+/-0.7) microg/mL at 5.7 h for the oral route. The oral availability of sulfadimethoxine relative to the i.p. route was 4.6%, while the oral availability of ormetoprim relative to the i.p. route was 78.5%. Due to the nonconstant ratio of these drugs in the plasma of the animal, the actual drug ratio to use for determining minimum inhibitory concentration (MIC) is unclear. Using the ratio of the total amount of each drug that is absorbed as a surrogate for the mean actual ratio may be the best alternative to current methods. Using this ratio as determined in these studies, (2.14:1 sulfadimethoxine:ormetoprim) to determine the MICs the single 50 mg/kg oral dose of the 5:1 combination of sulfadimethoxine and ormetoprim appears to provide plasma concentrations high enough to inhibit the growth of Yersinia ruckeri, Edwardsiella tarda, and Escherichia coli.     

Pharmacokinetics of lamivudine in cats

OBJECTIVE: To characterize the pharmacokinetics of lamivudine (3TC) in cats. ANIMALS: 6 sexually intact 9-month-old barrier-reared domestic shorthair cats. PROCEDURE: Cats were randomly alloted into 3 groups, and lamivudine (25 mg/kg) was administered i.v., intragastrically (i.g.), and p.o. in a 3-way crossover study design with 2-week washout periods between experiments. Plasma samples were collected for 12 hours after drug administration, and lamivudine concentrations were determined by high-performance liquid chromatography. Maximum plasma concentrations (Cmax), time to reach Cmax (Tmax), and bioavailability were compared between i.g. and p.o. routes. Area under the curve (AUC) and terminal phase half-life (t(1/2)) among the 3 administration routes were also compared. RESULTS: Plasma concentrations of lamivudine declined rapidly with a t(1/2) of 1.9 +/- 0.21 hours, 2.6 +/- 0.66 hours, and 2.7 +/- 1.50 hours after i.v., i.g., and p.o. administration, respectively. Total body clearance and steady-state volume of distribution were 0.22 +/- 0.09 L/h/kg and 0.60 +/- 0.22 L/kg, respectively. Mean Tmax for i.g. administration (0.5 hours) was significantly shorter than Tmax for p.o. administration (1.1 hours). The AUC after i.v., i.g., and p.o. administration was 130 +/- 55.2 mg x h/L, 115 +/- 97.5 mg x h/L, and 106 +/- 94.9 mg x h/L, respectively. Lamivudine was well absorbed after i.g. and p.o. administration with bioavailability values of 88 +/- 45% and 80 +/- 52%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Cats had a shorter t(1/2) but slower total clearance of lamivudine, compared with humans. Plasma concentrations of lamivudine were maintained above the minimum effective concentration for inhibiting FIV replication by 50% (0.14 microM [0.032 microg/mL] for wild-type FIV clinical isolate) for at least 12 hours after i.v., i.g., or p.o. administration.     

Pharmacokinetics of zidovudine in cats

OBJECTIVE: To characterize the pharmacokinetics of zidovudine (AZT) in cats. ANIMALS: 6 sexually intact 9-month-old barrier-reared domestic shorthair cats. PROCEDURE: Cats were randomly alloted into 3 groups, and zidovudine (25 mg/kg) was administered i.v., intragastrically (i.g.), and p.o. in a 3-way crossover study design with 2-week washout periods between experiments. Plasma samples were collected for 12 hours after drug administration, and zidovudine concentrations were determined by high-performance liquid chromatography. Maximum plasma concentrations (Cmax), time to reach Cmax (Tmax), and bioavailability were compared between i.g. and p.o. routes. Area under the curve (AUC) and terminal phase half-life (t(1/2)) among the 3 administration routes were also compared. RESULTS: Plasma concentrations of zidovudine declined rapidly with t(1/2) of 1.4 +/- 0.19 hours, 1.4 +/- 0.16 hours, and 1.5 +/- 0.28 hours after i.v., i.g., and p.o. administration, respectively. Total body clearance and steady-state volume of distribution were 0.41 +/- 0.10 L/h/kg and 0.82 +/- 0.15 L/kg, respectively. Mean Tmax for i.g. administration (0.22 hours) was significantly shorter than Tmax for p.o. administration (0.67 hours). The AUC after i.v. and p.o. administration was 64.7 +/- 16.6 mg x h/L and 60.5 +/- 17.0 mg x h/L, respectively, whereas AUC for the i.g. route was significantly less at 42.5 +/- 9.41 mg x h/L. Zidovudine was well absorbed after i.g. and p.o. administration with bioavailability values of 70 +/- 24% and 95 +/- 23%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Cats had slower clearance of zidovudine, compared with other species. Plasma concentrations of zidovudine were maintained above the minimum effective concentration for inhibiting FIV replication by 50% (0.07 microM [0.019 microg/mL] for wild-type FIV clinical isolate) for at least 12 hours after i.v., i.g., or p.o. administration.     

Pharmacokinetics and endometrial tissue concentrations of enrofloxacin and the metabolite ciprofloxacin after i.v. administration of enrofloxacin to mares

Enrofloxacin was administered i.v. to five adult mares at a dose of 5 mg/kg. After administration, blood and endometrial biopsy samples were collected at regular intervals for 24 h. The plasma and tissue samples were analyzed for enrofloxacin and the metabolite ciprofloxacin by high-pressure liquid chromatography. In plasma, enrofloxacin had a terminal half-life (t(1/2)), volume of distribution (area method), and systemic clearance of 6.7 +/- 2.9 h, 1.9 +/- 0.4 L/kg, and 3.7 +/- 1.4 mL/kg/min, respectively. Ciprofloxacin had a maximum plasma concentration (Cmax) of 0.28 +/- 0.09 microg/mL. In endometrial tissue, the enrofloxacin Cmax was 1.7 +/- 0.5 microg/g, and the t(1/2) was 7.8 +/- 3.7 h. Ciprofloxacin Cmax in tissues was 0.15 +/- 0.04 microg/g and the t(1/2) was 5.2 +/- 2.0 h. The tissue:plasma enrofloxacin concentration ratios (w/w:w/v) were 0.175 +/- 0.08 and 0.47 +/- 0.06 for Cmax and AUC, respectively. For ciprofloxacin, these values were 0.55 +/- 0.13 and 0.58 +/- 0.31, respectively. We concluded that plasma concentrations achieved after 5 mg/kg i.v. are high enough to meet surrogate markers for antibacterial activity (Cmax:MIC ratio, and AUC:MIC ratio) considered effective for most susceptible gram-negative bacteria. Endometrial tissue concentrations taken from the mares after dosing showed that enrofloxacin and ciprofloxacin both penetrate this tissue adequately after systemic administration and would attain concentrations high enough in the tissue fluids to treat infections of the endometrium caused by susceptible bacteria.     

Pharmacokinetics, metabolism and renal clearance of flumequine in veal calves

The pharmacokinetics of flumequine was studied in 1-, 5- and 18-week-old veal calves. A two-compartment model was used to fit the plasma concentration-time curve of flumequine after the intravenous injection of 10 mg/kg of a 10% solution. The elimination half-life (t1/2 beta) of the drug ranged from 6 to 7 h. The Vd beta and ClB of 1-week-old calves (1.07 l/kg, 1.78 ml/min/kg) were significantly lower than those of 5-week-old (1.89 l/kg, 3.23 ml/min/kg) and 18-week-old calves (1.57 l/kg, 3.10 ml/min/kg). After the oral administration of 10 mg/kg of a 2% flumequine formulation mixed with milk replacer, the Cmax was highest in 1-week-old (9.27 micrograms/ml) and lowest in 18-week-old calves (4.47 micrograms/ml). The absorption was rapid (Tmax of approximately 3 h) and complete. When flumequine itself and a formulation containing 2% flumequine and 20 X 10(6) iu of colistin sulphate were mixed with milk replacer and administered at the same dose rate, absorption was incomplete and Cmax was lower. The main urinary metabolite of flumequine was the glucuronide conjugate (approximately 40% recovery within 48 h of intravenous injection) and the second most important metabolite was 7-hydroxy-flumequine (approximately 3% recovery within 12 h of intravenous injection). Only 3.2-6.5% was excreted in the urine unchanged. After oral administration a 'first-pass' effect was observed, with a significant increase in the excretion of conjugated drug. For 1-week-old calves it is recommended that the 2% formulation should be administered at a dose rate of 8 mg/kg every 24 h or 4 mg/kg every 12 h; for calves over 6 weeks old, the dose should be increased to 15 mg/kg every 24 h or 7.5 mg/kg every 12 h. The formulation containing colistin sulphate should be administered to 1-week-old calves at a flumequine dose of 12 mg/kg every 24 h or 6 mg/kg every 12 h.     

磺胺二甲嘧啶在黑鲪体内的药物代谢动力学和残留消除研究

在(14±1)℃水温条件下,对黑鲪单次口灌100 mg/kg体重的磺胺二甲嘧啶,进行药物代谢动力学研究。在(20±2)℃水温条件下,按照《中华人民共和国水产行业标准磺胺类药物水产养殖使用规范》推荐剂量对黑鮶连续5天口灌给予磺胺二甲嘧啶,研究其在黑鮶体内的残留消除规律。血浆、肌肉和肝脏样品采用高效液相色谱检测,DAS2.0药物代谢动力学软件对数据进行处理分析。结果表明磺胺二甲嘧啶在黑鲪血浆、肌肉和肝脏中均符合一室模型,肝脏、血液和肌肉中药物达峰时间分别为6 h,8 h和10 h;峰值浓度分别为26.45μg/g、25.57μg/g和31.15μg/g;连续多次给药后,黑鮶血液、肌肉、肝脏中药物浓度分别在给药后12d、14d、15d后小于最大残留限量要求(0.1mg/kg)。     

Residue depletion of thiamphenicol in the sea-bass

The residue depletion of thiamphenicol (TAP) was investigated in the sea-bass (Dicentrarchus labrax) after 5 days' treatment with medicated food at a dose of 15 or 30 mg/kg bw/day. Fish were sampled for blood and muscle + skin from 3 h until 14 days after treatment. Thiamphenicol concentrations were assayed by high performance liquid chromatography. Thiamphenicol concentrations measured 3 h after stopping treatment were 0.77 microg/mL and 0.91 (15 mg/kg dose) or 1.32 microg/mL and 1.47 microg/g (30 mg/kg dose), in plasma and muscle + skin, respectively. After a withdrawal of 3 days, plasma and tissue concentrations were: 0.08 microg/mL and 0.03 microg/g (lower dose) or 0.12 microg/mL and 0.06 microg/g (higher dose), respectively. Thiamphenicol was not detectable either in plasma or in tissues on days 7, 10 and 14 following withdrawal of the medicated food. Based on maximum residue levels (MRL) for TAP in fin fish, established at 50 microg/kg for muscle and skin in natural proportions, a withdrawal period of 5 and 6 days is proposed, after treatment at 15 or 30 mg/kg of TAP with medicated feed pellets, respectively, to avoid the presence of violative residues in the edible tissues of the sea-bass.     

Pharmacokinetics and tissue residue profiles of erythromycin in broiler chickens after different routes of administration

This study investigated the disposition kinetics and plasma availability of erythromycin in broiler chickens after single intravenous (i.v.), intramuscular (i.m.), subcutaneous (s.c.) and oral administrations (p.o.) of 30 mg kg(-1) b. wt. Tissue residue profiles were also studied after multiple intramuscular, subcutaneous, and oral administration of 30 mg kg(-1) b. wt., twice daily for three consecutive days. Plasma and tissue concentrations of erythromycin were determined using microbiological assay methods with Micrococcus luteus as the test organism. Following intravenous injection, plasma concentration-vs-time curves were best described by a two compartment open model. The decline in plasma drug concentration was bi-exponential with half-lives of (t(1/2alpha)) 0.19 h and (t(1/2beta)) 5.3 h for distribution and elimination phases, respectively. After intramuscular, subcutaneous and oral administration erythromycin at the same dose was detected in plasma at 10 min and reached its minimum level 8 h post-administration. The peak plasma concentration (Cmax) were 5.0, 5.3, and 6.9 microg x ml(-1) and were attained at 1.7, 1.4, and 1.3 h (Tmax), respectively. The elimination half-lives (T(1/2el)) were 3.9, 2.6, and 4.1 h and the mean residence times (MRT) were 3.5, 3.2, and 3.6 h, respectively. The systemic bioavailabilities were 92.5, 68.8, and 109.3%, respectively. In vitro protein binding percent of erythromycin in broiler plasma was ranged from 21 to 31%. The limit of quantification (LOQ) for the assay was 0.03 microg x ml(-1) in plasma and tissues. The tissue level concentrations were highest in the liver, and decreased in the following order: plasma > kidney > lung > muscle and heart. No erythromycin residues were detected in tissues and plasma after 24 h except in liver and kidney where it persisted during 48 h following intramuscular and oral administrations.     

Pharmacokinetics and tissue distribution of enrofloxacin and its active metabolite ciprofloxacin in calves

The purpose of this study was to establish the pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin in the plasma and interstitial fluid (ISF) following subcutaneous (s.c.) administration of enrofloxacin. Ultrafiltration probes were placed in the s.c. tissue, gluteal musculature, and pleural space of five calves. Each calf received 12.5 mg/kg of enrofloxacin. Plasma and ISF samples were collected for 48 h after drug administration and analyzed by high pressure liquid chromatography. Plasma protein binding of enrofloxacin and ciprofloxacin was measured using a microcentrifugation system. Tissue probes were well tolerated and reliably produced fluid from each site. The mean +/- SD plasma half-life was 6.8 +/- 1.2 and 7.3 +/- 1 h for enrofloxacin and ciprofloxacin, respectively. The combined (ciprofloxacin + enrofloxacin) peak plasma concentration (Cmax) was 1.52 microg/mL, and the combined area under the curve (AUC) was 25.33 microg/mL. The plasma free drug concentrations were 54% and 81% for enrofloxacin and ciprofloxacin, respectively, and free drug concentration in the tissue fluid was higher than in plasma. We concluded that Cmax/MIC and AUC/MIC ratios for free drug concentrations in plasma and ISF would meet suggested ratios for a targeted MIC of 0.06 microg/mL.     

Pharmacokinetics of flumequine in sheep after intravenous and intramuscular administration: bioavailability and tissue residue studies

The pharmacokinetic properties of flumequine and its metabolite 7-hydroxyflumequine were determined in six healthy sheep after single intramuscular (i.m.) and intravenous (i.v) injections at a dose of 6 mg/kg body weight. The tissue residues were determined in 20 healthy sheep after repeated i.m. administration with a first dose of 12 mg/kg and nine doses of 6 mg/kg. The flumequine formulation used was Flumiquil 3% Suspension Injectable®. The mean plasma concentrations of flumequine after i.v. administration were described by a three-compartment open model with a rapid distribution and a relatively slow elimination phase. The low value of volume of distribution at steady state (V_dss) (0.52 ± 0.24 L/kg) and high value of volume of distribution (V_dλ₃) (5.05 ± 3.47 L/kg) emphasized the existence of a small compartment with a slow rate of return to the central compartment. The mean elimination half-life was 11.5 h. The 7-hydroxyflumequine plasma levels represented 2.3% of the total area under the curve. The mean plasma concentrations of flumequine after i.m. administration were characteristic of a two-compartment model with a first order absorption. The mean maximal plasma concentration (1.83 ± 1.15 μg/mL) was obtained rapidly, i.e. 1.39 ± 0.71 h after the i.m. administration. The fraction of dose absorbed from the injection site was 85.00 ± 30.13%. The minimal concentrations of flumequine during repeated treatment were significantly lower in females than in males. Eighteen hours after the last repeated i.m. admini-stration, the highest concentration of flumequine was observed at the injection sites followed by kidney, liver, muscle and fat. The highest concentration of 7-hydroxyflumequine was observed in the kidney and was ten times lower than the flumequine concentration. The longest flumequine elimination half-life was observed in the fat.     

喹烯酮及其主要代谢物在猪体内的药动学研究

本试验旨在研究喹烯酮及其主要代谢物在猪体内的药物代谢动力学过程。将喹烯酮按40 mg/kg的剂量对7头猪进行灌胃给药,采用HPLC-MS/MS法测定血浆中喹烯酮及其主要代谢物的浓度,药代动力学软件WinNonlin 5.2处理血浆中药物浓度－时间数据。灌胃给药后猪血浆中能检测到原药和N1-脱氧喹烯酮、脱二氧喹烯酮及3-甲基喹噁啉-2-羧酸(MQCA)3种代谢物。喹烯酮的浓度－时间数据符合一级吸收一室开放模型,其主要药代动力学参数为:T_1/2Ka＝(0.97±0.08)h,T_1/2λz＝(2.79±0.16)h,CL＝(26.03±0.65)L/h·kg,Cmax＝(0.26±0.01)μg/mL,Tmax＝(2.23±0.06)h,AUC＝(1.54±0.04)h·μg/mL;采用统计矩法处理N1-脱氧喹烯酮和脱二氧喹烯酮的浓度－时间数据,N1-脱氧喹烯酮主要药代动力学参数为:Tmax＝(6.33±1.37)h,Cmax＝(8.81±2.08) ng/mL,T_1/2λz＝(3.03±1.27)h,AUC＝(0.07±0.01)h·ng/mL,MRT＝(6.58±0.40)h;脱二氧喹烯酮的主要药动学参数:Tmax＝(10.29±0.29)h,Cmax＝(6.20±1.11)ng/mL,T_1/2λz＝(5.84±2.78)h,AUC＝(0.15±0.01)h·ng/mL,MRT＝(3.64±0.72)h。同时,在少数时间点检测到代谢物MQCA。猪口服喹烯酮后,吸收较快,消除较慢。血浆中检测到N1-脱氧喹烯酮、脱二氧喹烯酮及3-甲基喹噁啉-2-羧酸3种代谢物,且浓度较低、消除缓慢。     

Pharmacokinetics of oxolinic acid in sea-bass, Dicentrarchus labrax (L., 1758), after a single rapid intravascular injection

The pharmacokinetics of oxolinic acid was studied in sea-bass ( Dicentrarchus labrax ). The fish were kept in seawater at 15.2°C with a 12 h/12 h photoperiod. Oxolinic acid was injected in the caudal vein of anaesthetized sea-bass in a single rapid intravascular administration at a dose of 10 mg/kg of body weight. Plasma concentrations of oxolinic acid were determined using two analytical methods, a classic plate diffusion bioassay using Escherichia coli and a high performance liquid chromatography (HPLC) using solid phase extraction with an internal standard and a U.V. detection. The mean recoveries were 99.6% and 110.8% and determination limits were 0.04 μg/mL and 0.02 μg/mL, for the bioassay and the HPLC respectively. Compared to other fish species, the oxolinic acid was rapidly (absorption half life, t_a1/2= 0.69 h) distributed to body tissues outside the blood volume (volume of central compartment, V_c= 0.4 L/kg) and presented a large volume of distribution (V_dss= 2.55 L/kg). Considering its disappearance from the central compartment (rate constant: central-eliminated, k ₁₀= 0.16 h^–1) and its total body clearance ( Cl _t= 0.066 L/kg.h), the elimination phase of the oxolinic acid in sea-bass was shorter than in trout kept in freshwater, and longer than in salmon in seawater. Consequently, the area under the concentration–time curve ( AUC = 157 μg.h/mL) and the mean residence time ( MRT = 42 h) were relatively low and short, respectively.     

Comparison of the effect of Sporobolus virginicus and Rhodes (Chloris gayana) hay diets on the absorption pattern of phenylbutazone in the camel (Camelus dromedarius)

The effect of feeding Sporobolus and Rhodes hay on phenylbutazone (4 g) relative absorption was examined in six camels using a two-period, two-sequence, two-treatment crossover design. Serum concentration of the drug was measured by high performance liquid chromatography. The measured values (means+/-SD) for Rhodes and Sporobolus hay, respectively, were Cmax 35.59+/-22.36 and 36.55+/-18.99 microg/mL, Tmax 26+/-2.53 and 26.3+/-1.97 h and AUC0-72 h 1552+/-872.6 and 1621+/-903.6 microg h/mL. Broad plateau concentrations of phenylbutazone in serum were observed between 12 and 36 h. There was no significant difference in any parameter between the two feeding regimens. Multiple peaks in serum concentration-time curve were observed, regardless of the type of grass available to and the animals prior to drug administration. It was concluded that the phasic absorption of phenylbutazone was a particular feature of hay feeding in camels, and the Sporobolus hay can be fed to camels without any effect on the rate and extent of phenylbutazone absorption compared to Rhodes grass hay.     

Effect of Cooking on Residues of the Quinolones Oxolinic Acid and Flumequine in Fish

Steffenak, I., V. Hormazabal and M. Yndestad: Effect of cooking on residues of the quinolones oxolinic acid and flumequine in fish. Acta vet. scand. 1994,35,299-301.– The effect of cooking on residues of the quinolones oxolinic acid and flumequine in fish was investigated. Salmon containing residues of oxolinic acid and flumequine was boiled or baked in the oven. Samples of raw and cooked muscle, skin, and bone, as well as of the water in which the fish was boiled and juice from the baked fish, were analysed. Oxolinic acid and flumequine did not degrade at the temperatures reached when cooking the fish. However, fish muscle free from drug residues may be contaminated during boiling and baking due to leakage of the drug from reservoirs in the fish.     

Pharmacokinetics of ceftriaxone after intravenous, intramuscular and subcutaneous administration to domestic cats

The pharmacokinetic properties of ceftriaxone, a third-generation cephalosporin, were investigated in five cats after single intravenous, intramuscular and subcutaneous administration at a dosage of 25 mg/kg. Ceftriaxone MICs for some gram-negative and positive strains isolated from clinical cases were determined. Efficacy predictor (t > MIC) was calculated. Serum ceftriaxone disposition was best fitted by a bicompartmental and a monocompartmental open models with first-order elimination after intravenous and intramuscular and subcutaneous dosing, respectively. After intravenous administration, distribution was fast (t1/2d 0.14 +/- 0.02 h) and moderate as reflected by the volume of distribution (V(d(ss))) of 0.57 +/- 0.22 L/kg. Furthermore, elimination was rapid with a plasma clearance of 0.37 +/- 0.13 L/h.kg and a t1/2 of 1.73 +/- 0.23 h. Peak serum concentration (Cmax), tmax and bioavailability for the intramuscular administration were 54.40 +/- 12.92 microg/mL, 0.33 +/- 0.07 h and 85.72 +/- 14.74%, respectively; and for the subcutaneous route the same parameters were 42.35 +/- 17.62 microg/mL, 1.27 +/- 0.95 h and 118.28 +/- 39.17%. Ceftriaxone MIC for gram-negative bacteria ranged from 0.0039 to >8 microg/mL and for gram-positive bacteria from 0.5 to 4 microg/mL. t > MIC was in the range 83.31-91.66% (10-12 h) of the recommended dosing interval (12 h) for Escherichia coli (MIC90 = 0.2 microg/mL).     

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.