Disposition of sulfadimidine and its N4-acetyl and hydroxy metabolites in horse plasma

The plasma disposition of sulfadimidine (SDM) and its metabolites N4-acetylsulfadimidine (N4-SDM), 6-hydroxymethyl-4-methyl-pyrimidine (SCH2OH) and 5-hydroxy-4,6-dimethyl-pyrimidine (SOH), was studied in three horses following intravenous administration of SDM at dose levels of 20 and 200 mg/kg in cross-over trials. The percentages of N4-SDM (0.58-0.90%), SOH (0.83-6.75%) and SCH2OH (0.38-0.71%) in plasma, expressed as a percentage of the total sulfonamide concentration, were small and their plasma concentrations were parallel with SDM from 4 h following administration. At high doses (200 mg/kg), the elimination half-life was slightly longer than at low doses (6.0, 10.5, 11.0 vs 5.0, 9.5, 9.5, respectively). The plasma protein binding was related to the dose; it was for the 20 and 200 mg/kg doses, respectively:SDM:61.5-73.3% and 50.5-52.1%; SOH: 47.1-71.0% and 36.7-39.5%, and for N4-SDM: 45.9-63.2% and 38.3-53.7%. The protein binding for SCH2OH, measured in samples obtained at the high dose level, ranged from 13.8 to 20.0%.     

Pharmacokinetics of an ampicillin/sulbactam (2:1) combination in rabbits

The pharmacokinetics of a 2:1 ampicillin-sulbactam combination in six rabbits, after intravenous and intramuscular injection at a single dosage of 20 mg/kg bodyweight (13.33 mg/kg of sodium ampicillin and 6.67 mg/kg of sodium sulbactam) were investigated by using a high performance liquid chromatographic method for determining plasma concentrations. The plasma concentration-time curves were analysed by compartmental pharmacokinetic and noncompartmental methods. The disposition curves for both drugs were best described by an open two-compartment model after intravenous administration and a one-compartment model with first order absorption after intramuscular administration. The apparent volumes of distribution calculated by the area method for ampicillin and sulbactam were 0.62 +/- 0.09 and 0.45 +/- 0.05 L/kg, respectively, and the total body clearances were 0.65 +/- 0.04 and 0.42 +/- 0.05 L/kg h, respectively. The elimination half-lives of ampicillin after intravenous and intramuscular administration were 0.64 +/- 0.11 and 0.63 +/- 0.16 h, respectively, whereas for sulbactam the half-lives were 0.74 +/- 0.12 and 0.77 +/- 0.17 h, respectively. The bioavailability after intramuscular injection was high and similar in both drugs (73.34 +/- 10.08% for ampicillin and 83.20 +/- 7.41% for sulbactam). The mean peak plasma concentrations of ampicillin and sulbactam were reached at similar times (0.20 +/- 0.09 and 0.34 +/- 0.15 h, respectively) and peak concentrations were also similar but nonproportional to the dose of both products administered (13.07 +/- 3.64 mg/L of ampicillin and 8.42 +/- 1.74 mg/L of sulbactam). Both drugs had similar pharmacokinetic behaviour after intramuscular administration in rabbits.     

Pharmacokinetics and tissue residues of pefloxacin and its metabolite norfloxacin in broiler chickens

1. The pharmacokinetics of pefloxacin and its active metabolite norfloxacin were investigated in chickens after a single oral administration of pefloxacin at a dosage of 10 mg/kg. To characterise the residue pattern, another group of chickens was given 10 mg of pefloxacin/kg body once daily for 4 d by oral route; the tissue concentrations of pefloxacin and norfloxacin were determined at 1, 5 and 10 d after the last administration of the drug. 2. The concentrations of pefloxacin and norfloxacin in plasma and tissues were determined by HPLC assay. The limit of detection for pefloxacin and norfloxacin was 0.03 microg/ml in plasma or microg/g in tissue. 3. The plasma concentration-time data for pefloxacin and norfloxacin were characteristic of a one-compartment open model. The elimination half-life, maximum plasma drug concentration, time to reach maximum plasma drug concentration and mean residence time of pefloxacin were 8.74 +/- 1.48 h, 3.78 +/- 0.23 microg/ml, 3.33 +/- 0.21 h and 14.32 +/- 1.94 h, respectively, whereas the respective values of these variables for norfloxacin were 5.66 +/- 0.81 h, 0.80 +/- 0.07 microg/ml, 3.67 +/- 0.21 h and 14.44 +/- 0.97 h. 4. Pefloxacin was metabolised to norfloxacin to the extent of 22%. 5. The concentrations of pefloxacin (microg/g) 24 h after the fourth dose of the drug declined in the following order: liver (3.20 +/- 0.40) > muscle (1.42 +/- 0.18) > kidney (0.69 +/- 0.04) > skin and fat (0.06 +/- 0.02). Norfloxacin was also detectable in all the tissues analysed except muscle. No drug and/or its metabolite was detectable in tissues except skin and fat 5 d after the last administration. The concentrations of pefloxacin and norfloxacin in skin and fat 10 d after the last dose of pefloxacin were 0.04 +/- 0.02 and 0.03 +/- 0.01 microg/g, respectively.     

Elimination half-lives of sulphadimethoxine and its N4-acetyl metabolite in tissues of laying hens

The depletion rates of sulphadimethoxine (SDM) and its metabolite N4-acetylsulphadimethoxine (N4-AcSDM) were estimated in blood and various tissues of laying hens. The tissue contents (ppm) of SDM and N4-AcSDM after the withdrawal of SDM, which was fed to hens at 400 ppm diet for 5 successive days, were determined by HPLC. The elimination half-life (t1/2) of N4-AcSDM in the liver, ovary and muscle was estimated to be 4.3 h with a 95% confidence interval from 3.6 to 5.3 h. No significant difference between t1/2 of N4-AcSDM in the tissues and that of SDM (4.4 h) in the blood, kidney, muscle, ovary and adipose tissue was observed. On the other hand, the t1/2 of N4-AcSDM in the kidney (8.1 h) was significantly longer than that in the above 3 tissues.     

Dose dependent disposition of sulphadimidine and of its N4-acetyl and hydroxy metabolites in plasma and milk of dairy cows

The disposition of sulphadimidine (SDM) and of its N4-acetyl (N4-SDM) and two hydroxy metabolites, 6-hydroxymethyl-(SCH2OH) and 5-hydroxyasulphadimidine (SOH), was studied in plasma and milk of dairy cows following intramuscular or intravenous administration of sulphadimididine-33.3% at doses of 10, 45, 50, and 100 mg/kg. The main metabolite in plasma as well as in milk was SCH2OH. The metabolite percentages, the final plasma elimination half-lives, and the time of peak SDM concentrations in milk are presented for different dosages. The concentrations of SDM and its metabolites in milk ran parallel to those in plasma beyond 4 hours p.i. The metabolite concentrations in plasma and milk were lower than those of the parent SDM. Sulphate and glucuronide metabolites could not be detected in milk. At high doses (45 mg/kg or more) and SDM plasma concentrations exceeding 20 micrograms/ml, a capacity limited metabolism of SDM to SCH2OH was noticed, viz. a steady state concentration of SCH2OH and a biphasic elimination pattern for SDM and SCH2OH in plasma and milk. The mean ultrafiltrate ratios of the milk to plasma concentrations with respect to SDM, SCH2OH, SOH, and N4-SDM were: 0.69, 0.22, 020, and 0.63, respectively. The total amount of SDM and its metabolites recovered from the milk after milking twice daily over the whole experimental time was less than 2% of the applied dose. A bioassay method allowed of detecting qualitatively SDM concentrations exceeding 0.2 micrograms/ml in plasma or milk. Withholding times for edible tissues and milk are suggested.     

Pharmacokinetics of florfenicol and its major metabolite, florfenicol amine, in rabbits

The pharmacokinetics of florfenicol and its active metabolite florfenicol amine were investigated in rabbits after a single intravenous (i.v.) and oral (p.o.) administration of florfenicol at 20 mg/kg bodyweight. The plasma concentrations of florfenicol and florfenicol amine were determined simultaneously by an LC/MS method. After i.v. injection, the terminal half-life (t(1/2lambdaz)), steady-state volume of distribution, total body clearance and mean residence time of florfenicol were 0.90 +/- 0.20 h, 0.94 +/- 0.19 L/kg, 0.63 +/- 0.06 L/h/kg and 1.50 +/- 0.34 h respectively. The peak concentrations (C(max)) of florfenicol (7.96 +/- 2.75 microg/mL) after p.o. administration were observed at 0.90 +/- 0.38 h. The t(1/2lambdaz) and p.o. bioavailability of florfenicol were 1.42 +/- 0.56 h and 76.23 +/- 12.02% respectively. Florfenicol amine was detected in all rabbits after i.v. and p.o. administration. After i.v. and p.o. administration of florfenicol, the observed Cmax values of florfenicol amine (5.06 +/- 1.79 and 3.38 +/- 0.97 microg/mL) were reached at 0.88 +/- 0.78 and 2.10 +/- 1.08 h respectively. Florfenicol amine was eliminated with an elimination half-life of 1.84 +/- 0.17 and 2.35 +/- 0.94 h after i.v. and p.o. administration respectively.     

Pharmacokinetics of sulphamethoxazole in calves and cows

The kinetics of sulphamethoxazole (SMZ) in plasma and milk, and its metabolism, protein binding and renal clearance were studied in three newborn calves and two dairy cows after intravenous administration. SMZ was predominantly acetylated; no hydroxy and glucuronide derivatives could be detected in plasma and urine. Age-dependent pharmacokinetics and metabolism of SMZ were observed. The plasma concentration-time curves of the N4-acetyl metabolite in the elimination phase were parallel to those of the parent drug; the N4-acetyl metabolite plasma percentage depended on age and ranged between 100% (new-born) to 24.5% (cow). SMZ was rapidly eliminated (elimination half-lives: 2.0-4.7 h) and exhibited a relatively small distribution volume (VDarea: 0.44-0.57 l/kg). SMZ was excreted predominantly by glomerular filtration, while its N4-acetyl metabolite was actively eliminated by tubular secretion.     

Pharmacokinetics and preliminary observations of behavioral changes following administration of midazolam to dogs

The pharmacokinetics of midazolam were investigated following intravenous and intramuscular administration of 0.5 mg of midazolam hydrochloride/kg of body weight to five healthy mixed-breed dogs. One dog also received the same dose of midazolam by oral and rectal routes. The disposition of midazolam following intravenous administration was characterized by very rapid and relatively extensive distribution followed by rapid elimination. Mean (+/- SD) apparent volume of distribution was 3.0 +/- 0.9 l/kg, mean elimination half-life was 77 +/- 18 min, and clearance was 27 +/- 3 ml/kg/min. Following intramuscular administration, absorption was rapid and complete. A mean peak midazolam concentration of 549 +/- 121 ng/ml was reached within 15 min, and systemic availability was over 90% in each dog. Oral administration to one dog resulted in peak midazolam concentrations within 10 min and a systemic availability of 69%. Rectal administration to the same dog yielded very low systemic availability. Midazolam was extensively bound to canine plasma proteins, with the unbound fraction representing less than 4% of the total plasma midazolam concentration. Plasma samples were also assayed for the presence of the major metabolites, 1-OH and 4-OH midazolam. Neither metabolite were detected, probably as a result of rapid elimination of these compounds by hepatic glucuronidation. Behavioral responses to administration of midazolam included initial signs of profound weakness, ataxia and transient agitation followed by a period of quiesence. A normal behavior pattern returned within 2 h of midazolam administration.     

Effect of age on the acetylation and deacetylation reactions of sulphadimidine and N4- acetylsulphadimidine in calves

Following intravenous (i.v.) or intramuscular (i.m.) adminstration of sulphadimidine (SDM), the pharmacokinetics of SDM and N₄-acetylsulphadimidine (N₄-SDM) were studied in plasma of calves from the first day of life to the age of about 6 months. An obvious age dependency was observed for the elimination half-life (t1/2) of SDM: the first day of life the t1/2 ranged between 13.5 and 17 h, and decreased in approximately 3 weeks to 4–6 h and remained constant from this time. The metabolite N₄-SDM, as a percentage of the total concentration of the sulphonamide measured in plasma of neonatal calves, ranged between 21.6 and 25.5% at the first day of life, declined in 3 weeks to approximately 12.8%, and at 5 till 9 weeks the final percentage was about 6.8%. Following administration of N₄-SDM, the elimination half-life of N₄-SDM was 3 h in an 8-day-old calf declined to 1.4–1.7 h in 4-week-old calves, and was 0.9 h in calves older than 11 weeks. The percentage of SDM (a metabolite of N₄-SDM) in plasma increased with time after injection from 5.5 to 62.8% of the total sulphonamide plasma concentration. This value was age-related. The total body clearance of N₄-SDM was three- to five-fold higher than that of SDM.     

Pharmacokinetics and bioavailability of 2-mercaptopropionylglycine administered intravenously and orally in dogs

The pharmacokinetic disposition of 2-mercaptopropionylglycine (2-MPG) given as a single intravenous injection and/or as a single oral dose was studied in 9 normal and 13 cystinuric dogs. After intravenous injection of approximately 10 or 20 mg/kg body weight the pharmacokinetics were best described by a three-exponential function. The first phase involved a distribution process apparently including establishment of drug-plasma protein and drug-tissue binding. The second phase involved rapid renal elimination and 60% of the drug was excreted within 3 h of administration. There was also a slow terminal third phase with a long half-life after both intravenous (t1/2 = 23 h) and oral (t1/2 = 22 h) administration. No dose dependency was observed. A deep pool of reversibly tissue-bound 2-MPG was indicated by a Vss of 3.3 +/- 0.9 l/kg body weight and the long terminal elimination phase. Total clearance was estimated as 4.1 +/- 0.9 ml/min/kg body weight. 2-MPG was eliminated mainly by renal excretion, but there was a difference in recovery of dose between normal and cystinuric dogs. During the first 24 h after intravenous and oral administration, 69% and 54%, respectively, of the drug was recovered in the urine of normal dogs. The corresponding figures in cystinuric dogs were 44% and 29%, respectively. The absolute bioavailability (FAUC) was 88 +/- 20% in normal dogs.     

Pharmacokinetics, renal clearance, tissue distribution, and residue aspects of sulphadimidine and its N4-acetyl metabolite in pigs

Pharmacokinetics and tissue distribution experiments were conducted in pigs to which sulphadimidine (SDM) was administered intravenously, orally, and intramuscularly at a dosage of 20 mg SDM/kg. SDM was acetylated extensively, but neither hydroxy metabolites nor their derivatives could be detected in plasma, edible tissues or urine. Following i.v. and two oral routes of administration, the N4-acetylsulphadimidine (N4-SDM) concentration-time curve runs parallel to that of SDM. The percentage of N4-SDM in plasma was in the range between 7 and 13.5% of the total sulphonamide concentration. The bioavailability of SDM administered in a drench was 88.9 +/- 5.4% and administered mixed with pelleted feed for 3 consecutive days it was 48.0 +/- 11.5%. The renal clearance of unbound SDM, which was urine flow related, was 1/7 of that of creatinine, indicating reabsorption of the parent drug. The unbound N4-SDM was eliminated three times faster than creatinine, indicating that tubular secretion was the predominant mechanism of excretion. After i.v. administration, 51.9% of the administered dose was recovered in urine within 72 h p.i., one quarter of which as SDM and three quarters as N4-SDM. Tissue distribution data obtained at 26, 74, 168, and 218 h after i.m. injection revealed that the highest SDM concentration was found in plasma. The SDM concentration in muscle, liver, and kidney ranged from one third to one fifth of that in plasma. The N4-SDM formed a minor part of the sulphonamide content in edible tissues, in which the SDM as well as the N4-SDM concentration parallelled the plasma concentrations. Negative results obtained with a semi-quantitative bioassay method, based on monitoring of urine or plasma, revealed that the SDM concentration levels in edible tissues were in that case below 0.1 mu/g tissue.     

Fish and antibiotics: pharmacokinetics of sulphadimidine in carp (Cyprinus carpio)

Pharmacokinetics, metabolism and clearance of sulphadimidine (SDM) were studied after a single intraperitoneal injection of SDM in carp at 20 degrees C. SDM was acetylated and hydroxylated to a small extent. The main metabolite was N4-acetyl derivative amounting only 2% of the total drug dose excreted; hydroxylation was less important (0.41% of the dose). The elimination half-life for SDM in carp was 17.5 h. The clearance values for SDM and its metabolites were equivalent. The importance of pharmacokinetic studies in different fish species is discussed.     

Morphine reduces spinal c-fos expression dose-dependently during experimental laparotomy in pigs: a combined pharmacokinetic and surgical study

The pharmacokinetics of intravenous morphine 2.5mg/kg (n=4) and 10mg/kg (n=4) in plasma and cerebrospinal fluid (CSF) of pigs was studied. Plasma half-life was 1.0+/-0.1h and the main metabolite was morphine-3-glucuronide, whereas morphine-6-glucuronide was negligible. CSF morphine concentration peaked after 20-30min (2.5mg/kg) and 60-120min (10mg/kg), and elimination half-life was 3.5+/-0.3h. Subsequently, the effect of morphine on surgery-induced spinal nociception in pigs subjected to unilateral laparotomy was evaluated by stereological quantification of the total number of Fos-like-immunoreactive (Fos-LI) spinal neurons of the dorsal horn. Surgery (n=4) induced 91,680+/-14,974 Fos-LI neurons ipsilaterally and morphine reduced this number to 45,771+/-8755 following the 2.5mg/kg dose (p<0.01; n=6) and 14,981+/-2327 following the 10mg/kg dose (p<0.001; n=6). These results indicate that morphine dose-dependently reduces the number of surgery-induced Fos-LI neurons in the spinal cord. As even a high dose of morphine does not reduce spinal c-fos expression to basal level, it may be appropriate to use other analgesics simultaneously with morphine during surgery.     

Pharmacokinetics, bioavailability and dosage regimen of sulphadimidine in camels (Camelus dromedarius) under hot, arid environmental conditions

A two-way crossover study was conducted in young Bikaneri camels (aged between 12 and 18 months) during the hot summer season to determine the bioavailability, pharmacokinetics and dosage regimens of sulphadimidine (SDM). A dose of 100 mg.kg-1 of SDM was used to study both the intravenous and oral pharmacokinetics of the drug. Analysis of the intravenous data according to a two-compartment pharmacokinetic model revealed that SDM was well distributed in the body (Vd(area):0.862 L.kg-1), had an overall body clearance of 0.035 +/- 0.019 L.h-1.kg-1 and the elimination of half-lives was in the range of 14.2 to 20.6 h. The mean maximum plasma SDM concentration following oral administration was 63.23 +/- 2.33 micrograms.mL-1, which was achieved 24 h after the oral administration. The mean bioavailability of SDM following oral administration was approximately 100%. To achieve and maintain the therapeutically satisfactory plasma sulphadimidine levels of > or = 50 micrograms.mL-1, the optimum dosage regimen for camels following either intravenous or oral administration would be 110 mg.kg-1 as the priming dose and 69 mg.kg-1 as the maintenance dose, to be repeated at 24 h intervals.     

Disposition kinetics of gentamicin following repeated parenteral administration in buffalo calves (Bubalus bubalis).

Disposition kinetics of gentamicin was determined in buffalo calves following repeated parenteral administration of 5 mg/kg body weight. The absorption (t1/2 Ka) and elimination half-life (t1/2 beta) were found to be 0.40 +/- 0.12 and 4.33 +/- 0.39 h, respectively. Statistical comparison of the values of pharmacokinetic determinants generated in this study with the corresponding values following single intramuscular injection at the same dose level as reported earlier by GARG and GARG, 1990, revealed that the consecutive administration of drug influenced the pharmacokinetics profile of gentamicin. Elimination half-life was significantly longer (P < 0.05). Since elimination rate constant value was significantly reduced, the subsequent dosage will have to be reduced particularly if kidney functions are not normal. Otherwise, dosage regimen need not be changed.     

Gentamicin pharmacokinetics in diabetic dogs

Reduction of the prolonged terminal elimination phase of gentamicin may be caused by diabetes mellitus, irrespective of the model of diabetes. To test this hypothesis, five normal dogs, three dogs with alloxan-induced diabetes mellitus, and four dogs with naturally occurring diabetes mellitus (all of which were given exogenous insulin to control hyperglycemia) were given 4.4 mg/kg gentamicin intravenously. Serum pharmacokinetics were analyzed using non-compartmental pharmacokinetics assuming a sum of exponential terms. Gentamicin pharmacokinetics during the first 8 h were the same in normal and diabetic dogs. Over 7 days, MRT in normal dogs (5830 +/- 2970 min, mean +/- SD) was longer (P less than 0.01) than in diabetic dogs (136 +/- 164 min). In diabetic dogs, Cls was greater (3.01 +/- 0.86 ml/min/kg) than in normal dogs (1.45 +/- 0.11 ml/min/kg; P less than 0.01), whereas Vd(ss) was smaller in diabetic dogs (0.405 +/- 0.508 l/kg) than in normal dogs (8.56 +/- 4.48 l/kg; P less than 0.01). Serum gentamicin concentrations were less than 0.020 microgram/ml by 2 days in all of the diabetic dogs, but were 0.048 +/- 0.018 microgram/ml at 7 days in normal dogs. Thus, diabetes mellitus, either induced by alloxan administration or naturally occurring, abolished the terminal elimination phase of gentamicin disposition in a non-rodent species.     

Influence of general anaesthesia on the pharmacokinetics of intravenous fentanyl and its primary metabolite in horses

REASONS FOR PERFORMING STUDY: In order to evaluate its potential as an adjunct to inhalant anaesthesia in horses, the pharmacokinetics of fentanyl must first be determined. OBJECTIVES: To describe the pharmacokinetics of fentanyl and its metabolite, N-[1-(2-phenethyl-4-piperidinyl)maloanilinic acid (PMA), after i.v. administration of a single dose to horses that were awake in Treatment 1 and anaesthetised with isoflurane in Treatment 2. METHODS: A balanced crossover design was used (n = 4/group). During Treatment 1, horses received a single dose of fentanyl (4 microg/kg bwt, i.v.) and during Treatment 2, they were anaesthetised with isoflurane and maintained at 1.2 x minimum alveolar anaesthetic concentration. After a 30 min equilibration period, a single dose of fentanyl (4 microg/kg bwt, i.v.) was administered to each horse. Plasma fentanyl and PMA concentrations were measured at various time points using liquid chromatography-mass spectrometry. RESULTS: Anaesthesia with isoflurane significantly decreased mean fentanyl clearance (P < 0.05). The fentanyl elimination half-life, in awake and anaesthetised horses, was 1 h and volume of distribution at steady state was 0.37 and 0.26 l/kg bwt, respectively. Anaesthesia with isoflurane also significantly decreased PMA apparent clearance and volume of distribution. The elimination half-life of PMA was 2 and 1.5 h in awake and anaesthetised horses, respectively. CONCLUSIONS AND POTENTIAL RELEVANCE: Pharmacokinetics of fentanyl and PMA in horses were substantially altered in horses anaesthetised with isoflurane. These pharmacokinetic parameters provide information necessary for determination of suitable fentanyl loading and infusion doses in awake and isoflurane-anaesthetised horses.     

Pharmacokinetics of sulfadimethoxine and sulfamethoxazole in combination with trimethoprim after intravenous administration to healthy and pneumonic pigs

The pharmacokinetics of two sulfonamide/trimethoprim combinations were investigated after intravenous administration to clinically healthy pigs and to the same pigs following a challenge with Actinobacillus pleuropneumoniae toxins. Endobronchial challenge with A.pleuropneumoniae toxins resulted in fever, increased white blood cell counts and decreased water and feed consumption. Healthy, as well as febrile, pigs were given sulfadimethoxine (SDM) or sulfamethoxazole (SMX) intravenously at a dose of 25 mg/kg b.w. in combination with 5 mg trimethoprim (TMP) per kg body weight. The pharmacokinetic parameters of the sulfonamides as well as their main metabolites (acetyl sulfonamides) were not significantly different in healthy and febrile pigs. In healthy and pneumonic pigs, the mean elimination half-lives of SDM were 12.9 h and 13.4 h, respectively, those of SMX 2.5 h and 2.7 h, respectively, and those of TMP 2.8 h and 2.6 h, respectively. Distribution volumes in healthy and febrile pigs of SDM and SMX varied between 0.2 and 0.4 L/kg, and those of TMP between 1.1 and 1.6 L/kg. The mean AUC of TMP was decreased and the volume of distribution and total body clearance of TMP were increased in febrile pigs. Protein binding of the drugs and metabolites studied were not significantly changed after toxin-induced fever. The extent of protein binding of SDM, SMX and TMP was in the range 94–99%, 45–56% and 40–50%, respectively. Based on knowledge of in vitro antimicrobial activity of the drug combinations against A.pleuropneumoniae it was concluded that after intravenous administration of the dose administered (30 mg/kg of the combination preparations) to healthy and pneumonic pigs, plasma concentrations of SMX and TMP were above the concentration required for growth inhibition of 50% of A., pleuropneumoniae strains for approximately 16 h, whereas bacteriostatic plasma concentrations of SDM were still present after TMP had been eliminated from plasma. Because of similar elimination half-lives of SMX and TMP in pigs this combination is preferred to the combination of SDM with TMP.     

Pharmacokinetics of miocamycin following intravenous administration to cattle

The plasma pharmacokinetics for a single intravenous dose (10 mg/kg body weight) of miocamycin (a 16-membered macrolide drug) was investigated in Holando Argentino cattle (n = 5). Blood drug concentrations were determined by a microbiological method and data were best-fitted to a two-compartment open model. The pharmacokinetic profile consisted of a short distribution phase (t1/2 alpha = 7.41 +/- 0.53 min), followed by an extended terminal elimination phase (t1/2 beta = 2.49 +/- 0.23 h). The volume of distribution at steady-state was large (2.13 +/- 0.17 l/kg), suggesting extensive tissue distribution, the clearance value was 0.60 +/- 0.03 l/h.     

Pharmacokinetics of cefepime administered by i.v. and i.m. routes to ewes

The pharmacokinetics of cefepime were studied following i.v. and i.m. administration of 20 mg/kg in 10 ewes. Following i.v. administration of a single dose, the plasma concentration-time curves of cefepime were best fitted using a two-compartment open model. The elimination half-life (t(1/2beta)) was 1.76 +/- 0.07 h, volume of distribution at steady-state [V(d(ss))] was 0.32 +/- 0.01 L/kg and total body clearance (Cl(B)) was 2.37 +/- 0.05 mL/min.kg. Following i.m. administration, the drug was rapidly absorbed with an absorption half-life (t(1/2ab)) of 0.49 +/- 0.05 h, maximum plasma concentration (Cmax) of 31.9 +/- 1.5 mug/mL was attained at (tmax) 1.1 +/- 0.2 h and the drug was eliminated with an elimination half-life (t(1/2el)) of 2.06 +/- 0.11 h. The systemic bioavailability (F) after i.m. administration of cefepime was 86.8 +/- 7.5%. The extent of plasma protein binding measured in vitro was 14.8 +/- 0.54%. The drug was detected in urine for 36 h postadministration by both routes.