Pharmacokinetics of tobramycin in the camel

A/Hadi, A.A., Wasfi, I.A., Gadir, F.A., Amiri, M.H., Bashir, A.K. Baggot, J.D. Pharmacokinetics of tobramycin in the camel. J. vet. Pharmacol. Therap. 17 . 48–51.
The pharmacokinetics of tobramycin were determined in six healthy camels (Camelus dromedarius) following the intravenous (i.v.) and intramuscular (i.m. administration of single doses of tobramycin sulphate (40 mg/ml). The half-life to tobramycin was 189 ± 21 min and the mean residence time was 254 ± 26 min. The apparent volume of distribution (area method) was 245 ± 21 ml/kg. while volume of the central compartment of the two-compartment pharmaco-kinetic model was 110 ± 12 ml/kg. The clearance (systemic) of tobramycin was 0.90 ± 0.10 ml/min/kg. Values of the pharmacokinetic parameters suggest that glomerular filtration rate is lower in camels than in other ruminant species, horses, dogs and cats. Following i.m. administration of the dose (1.0 mg/kg), the drug was rapidly absorbed with peak serum concentration of 3.32 ± o.59 g/ml at 20–30 min; the absorption half-life was 3.9 ± 0.9 min. The systemic availability of tobramycin was 90.7 ± 14.4%. The apparent half-life was 201 ±40 min, which was not significantly longer than the half-life following i.v. administration of the drug. Based on the pharmacokinetic values obtained in this study, a dosing rate of 2.5 mg/kg administered by i.m. injection at 12-h intervals can be recommended. This dosage regimen should achieve an average steady state serum concentration of 4 g/ml with peak serum concentration approaching, but not exceeding, 10 g/ml.     

Pharmacokinetics, metabolism and urinary detection time of flunixin after intravenous administration in camels

The pharmacokinetics of flunixin were determined after an intravenous dose of 1.1 mg/kg body weight in six camels and 2.2 mg/kg body weight in four camels. The data obtained (mean ±  SEM) for the low and high dose, respectively, were as follows:
  The elimination half-lives ( t _½β) were 3.76 ± 0.24 and 4.08 ± 0.49 h, the steady state volumes of distribution ( V d_ss) were 320.61 ± 38.53 and 348.84 ± 35.36 mL/kg body weight, total body clearances ( Cl _T) were 88.96 ± 6.63 and 84.86 ± 4.95 mL/h/kg body weight and renal clearances ( Cl _r) were 0.52 ± 0.09 and 0.62 ± 0.18 mL/h/kg body weight. A hydroxylated metabolite of flunixin was identified by gas chromatography/mass spectrometry (GC/MS) under electron and chemical ionization and its major fragmentation pattern was verified by tandem mass spectrometry (GC/MS/MS) using neutral loss, daughter and parent scan modes. The detection times for flunixin and its hydroxylated metabolite in urine after an intravenous (i.v.) dose of 2.2 mg/kg body weight were 96 and 48 h, respectively.     

The pharmacokinetics and metabolism of meloxicam in camels after intravenous administration

The pharmacokinetics and metabolism of meloxicam was studied in camels (Camelus dromedarus) (n = 6) following intravenous (i.v.) administration of a dose of 0.6 mg·kg/body weight. The results obtained (mean ± SD) were as follows: the terminal elimination half-life (t(1/2β) ) was 40.2 ± 16.8 h and total body clearance (Cl(T) ) was 1.94 ± 0.66 mL·kg/h. The volume of distribution at steady state (V(SS)) was 92.8 ± 13.7 mL/kg. One metabolite of meloxicam was tentatively identified as methylhydroxy meloxicam. Meloxicam and metabolite were excreted unconjugated in urine. Meloxicam could be detected in plasma 10 days following i.v. administration in camels using a sensitive liquid chromatography tandem mass spectrometry (LC/MS/MS) method.     

Pharmacokinetics of erythromycin in nonlactating and lactating goats after intravenous and intramuscular administration

The objectives of this work were to compare the pharmacokinetics of erythromycin administered by the intramuscular (i.m.) and intravenous (i.v.) routes between nonlactating and lactating goats and to determine the passage of the drug from blood into milk. Six nonpregnant, nonlactating and six lactating goats received erythromycin by the i.m. (15 mg/kg) and the i.v. (10 mg/kg) routes of administration. Milk and blood samples were collected at predetermined times. Erythromycin concentrations were determined by microbiological assay. Results are reported as mean +/- SD. Comparison of the pharmacokinetic profiles between nonlactating and lactating animals after i.v. administration indicated that significant differences were found in the mean body clearance (8.38 +/- 1.45 vs. 3.77 +/- 0.83 mL/kg x h respectively), mean residence time (0.96 +/- 0.20 vs. 3.18 +/- 1.32 h respectively), area under curve from 0 to 12 h (AUC(0-12)) (1.22 +/- 0.22 vs. 2.76 +/- 0.58 microg x h/mL respectively) and elimination half-life (1.41 +/- 1.20 vs. 3.32 +/- 1.34 h); however, only AUC(0-12) showed significant differences after the i.m. administration. Passage of erythromycin in milk was high (peak milk concentration/peak serum concentration, 2.06 +/- 0.36 and AUC(0-12milk)/AUC(0-12serum),6.9 +/- 1.05 and 2.37 +/- 0.61 after i.v. and i.m. administrations respectively). We, therefore, conclude that lactation affects erythromycin pharmacokinetics in goats.     

Pharmacokinetics and metabolism of ketoprofen after intravenous and intramuscular administration in camels

The pharmacokinetics of ketoprofen were determined after an intravenous (i.v.) and intramuscular (i.m.) dose of 2.0 mg/kg body weight in five camels (Camelus dromedarius) using gas chromatography/mass spectrometry (GC/MS). The data obtained (median and range) following i.v. administration was as follows: the elimination half-life (t(1/2beta)) was 4.16 (2.65-4.29) h, the steady state volume of distribution (Vss) was 130.2 (103.4-165.3) mL/kg, volume of distribution (area method) (Vd(area)) was 321.5 (211.4-371.0) mL/kg, total body clearance (Cl) was 1.00 (0.88-1.08) mL/min x kg and renal clearance was 0.01 (0.003-0.033) mL/min x kg. Following i.m. administration, the drug was rapidly absorbed with peak serum concentration of 12.2 (4.80-14.4) microg/mL at 1.50 (1.00-2.00) h. The systemic availability of ketoprofen was complete. The apparent half-life was 3.28 (2.56-4.14) h. A hydroxylated metabolite of ketoprofen was identified by (GC/MS) under electron impact (EI) and chemical ionization (CI) scan modes. The detection times for ketoprofen and hydroxy ketoprofen in urine after an intravenous (i.v.) dose of 3.0 mg/kg body weight was 24.00 and 70.00 h, respectively. Serum protein binding of ketoprofen at 20 microg/mL was extensive; (99.1+/-0.15%).     

Pharmacokinetics of cefoperazone in horses

The pharmacokinetics and bioavailabilty of cefoperazone (CPZ) were studied following intravenous (IV) and intramuscular (IM) administration of single doses (30 mg/kg) to horses. Concentrations in serum, urine and synovial fluid samples were measured following IV administration. CPZ concentrations in serum, synovial fluid and spongy bone samples were measured following IM administration. After IV administration a rapid distribution phase ( t _1/2(α):4.22 ± 2.73 min) was followed by a slower elimination phase ( t 1/2(β) 0.77 ± 0.19 h). The apparent volume of distribution was 0.68 ± 0.10 L/kg. Mean synovial fluid peak concentration was 5.76 ± 0.74 μg/mL. After IM administration a bioavailability of 42.00±5.33% was obtained. Half-life of absorption was 2.51 ± 0.72 min and t _1/2(β) was 1.52±0.15 h. The mean synovial fluid and spongy bone peak concentrations at 2 h after IM administration were 2.91±0.85 μg/mL and 5.56±0.70 μg/mL, respectively.     

Pharmacokinetics of intravenous and intramuscular tramadol in llamas

The purpose of this study was to determine the pharmacokinetics of tramadol and its metabolite M1 after intravenous and intramuscular administration to llamas. Tramadol, a centrally acting analgesic whose efficacy is a result of complex interactions between opiate, adrenergic and serotonin receptor systems, has been used clinically to treat moderate to severe pain in humans. The pharmacokinetic parameters of tramadol and M1 in plasma were examined following intravenous and intramuscular administration to six healthy male llamas. Tramadol half-life, volume of distribution at steady-state and clearance after intravenous administration were 2.12 ± 0.37 h, 4.02 ± 1.16 L/kg and 1728.73 ± 152.82 mL/h/kg, respectively. The bioavailability was 110 ± 21% and half-life 2.54 ± 0.31 h following intramuscular administration of tramadol. M1 had a half-life of 10.40 ± 2.90 h and 7.71 ± 0.54 h following intravenous and intramuscular administration of tramadol.     

Pharmacokinetics and disposition of clenbuterol in the horse

The pharmacokinetics of clenbuterol (CLB) following a single intravenous (i.v.) and oral (p.o.) administration twice daily for 7 days were investigated in thoroughbred horses. The plasma concentrations of CLB following i.v. administration declined mono-exponentially with a median elimination half-life ( t _1/2k) of 9.2 h, area under the time–concentration curve ( AUC ) of 12.4 ng·h/mL, and a zero-time concentration of 1.04 ng/mL. Volume of distribution ( V _d) was 1616.0 mL/kg and plasma clearance ( Cl ) was 120.0 mL/h/kg. The terminal portion of the plasma curve following multiple p.o. administrations also declined mono-exponentially with a median elimination half-life ( t _1/2k) of 12.9 h, a Cl of 94.0 mL/h/kg and V _d of 1574.7 mL/kg. Following the last p.o. administration the baseline plasma concentration was 537.5 ± 268.4 and increased to 1302.6 ± 925.0 pg/mL at 0.25 h, and declined to 18.9 ± 7.4 pg/mL at 96 h. CLB was still quantifiable in urine at 288 h following the last administration (210.0 ± 110 pg/mL). The difference between plasma and urinary concentrations of CLB was 100-fold irrespective of the route of administration. This 100-fold urine/plasma difference should be considered when the presence of CLB in urine is reported by equine forensic laboratories.     

The pharmacokinetics, metabolism and urinary detection time of tramadol in camels

The pharmacokinetics of tramadol in camels (Camelus dromedarius) were studied following a single intravenous (IV) and a single intramuscular (IM) dose of 2.33 mg kg(-1) bodyweight. The drug's metabolism and urinary detection time were also investigated. Following both IV and IM administration, tramadol was extracted from plasma using an automated solid phase extraction method and the concentration measured by gas chromatography-mass spectrometry (GC/MS). The plasma drug concentrations after IV administration were best fitted by an open two-compartment model. However a three-compartment open model best fitted the IM data. The results (means+/-SEM) were as follows: after IV drug administration, the distribution half-life (t(1/2)(alpha)) was 0.22+/-0.05 h, the elimination half-life (t(1/2)(beta)) 1.33+/-0.18 h, the total body clearance (Cl(T)) 1.94+/-0.18 L h kg(-1), the volume of distribution at steady state (Vd(ss)) 2.58+/-0.44 L kg(-1), and the area under the concentration vs. time curve (AUC(0-infinity)) 1.25+/-0.13 mg h L(-1). Following IM administration, the maximal plasma tramadol concentration (C(max)) reached was 0.44+/-0.07 microg mL(-1) at time (T(max)) 0.57+/-0.11h; the absorption half-life (t(1/2 ka)) was 0.17+/-0.03 h, the (t(1/2)(beta)) was 3.24+/-0.55 h, the (AUC(0-infinity)) was 1.27+/-0.12 mg h L(-1), the (Vd(area)) was 8.94+/-1.41 L kg(-1), and the mean systemic bioavailability (F) was 101.62%. Three main tramadol metabolites were detected in urine. These were O-desmethyltramadol, N,O-desmethyltramadol and/or N-bis-desmethyltramadol, and hydroxy-tramadol. O-Desmethyltramadol was found to be the main metabolite. The urinary detection times for tramadol and O-desmethyltramadol were 24 and 48 h, respectively. The pharmacokinetics of tramadol in camels was characterised by a fast clearance, large volume of distribution and brief half-life, which resulted in a short detection time. O-Desmethyltramadol detection in positive cases would increase the reliability of reporting tramadol abuse.     

Comparative pharmacokinetics of theophylline in camels (Camelus dromedarius) and goats (Caprus hircus)

A comparative randomized crossover study was conducted to determine the pharmacokinetics of theophylline in male and female camels (Camelus dromedarius) and goats (Caprus hircus). Theophylline is an established 'probe drug' to evaluate the drug metabolizing enzyme activity of animals. It was administered by the intravenous (i.v.) route and then intramuscularly (i.m.) at a dose of 2 mg/kg. The concentration of the drug in plasma was measured using a high-performance liquid chromatography (HPLC) technique on samples collected at frequent intervals after administration. Following i.v. injection, the overall elimination rate constant (lambda z,) in goats was 0.006 +/- 0.00076/min and in camels was 0.0046 +/- 0.0008/min (P < 0.01). The elimination half-life (t 1/2 lambda z) in goats (112 .7 min) was lower than in camels (154.7 min) (P < 0.01). The apparent volume of distribution (Vz) and the total body clearance (Cl) in goats were 1440.1 +/- 166.6 ml/kg and 8.9 +/- 1.4 ml/min/kg, respectively. The corresponding values in camels were 1720.3 +/- 345.3 ml/kg and 6.1 +/- 1.0 ml/min/kg, respectively. After i.m. administration, theophylline reached a peak plasma concentration (Cmax) of 1.8 +/- 0.1 and 1.7 +/- 0.2 microg/ml at a post-injection time (Tmax) of 67.5 +/- 8.6 and 122.3 +/- 6.7 min in goats and camels, respectively. The mean bioavailability (T) in both goats and camels was 0.9 +/- 0.2. The above data suggest that camels eliminate theophylline at a slower rate than goats.     

Comparative pharmacokinetics of diminazene in lactating goats and sheep

The pharmacokinetic aspects of diminazene aceturate were studied in lactating goats and sheep after single intravenous and intramuscular administrations of 3.5 mg/kg b.wt. Plasma and milk concentrations were determined by use of reversed phase high-performance liquid chromatography (HPLC) after ion-pair extraction. Following intravenous injection, the disposition of diminazene in goats and sheep conformed to a two-compartment model with rapid distribution and slower elimination phases. Values of (t1/2 beta) were obtained indicating a slower final disappearance of the drug from plasma of sheep (21.17 h) than in goats (16.39 h). Diminazene concentrations were maintained for more than 4 days in the plasma of goats and sheep. In both species of animals, diminazene was rapidly absorbed following intramuscular administration of 3.5 mg/kg b.wt. The peak plasma concentrations (Cmax) were 7.00 and 8.11 micrograms/ml and were attained at (Tmax) 0.92 and 1.12 hours in goats and sheep, respectively. The elimination half-life (t1/2el) of diminazene after intramuscular administration was shorter in goats (16.54 h) than in sheep (18.80 h). Systemic bioavailabilities (F%) of diminazene after intramuscular administration were 94.94% and 82.64% in goats and sheep, respectively. Diminazene could be detected in milk of goats and sheep within 10 min post-injection. Milk concentrations of the drug were lower in goats than in sheep and were detected for 5 and 6 days following both routes of administration, respectively.     

Pharmacokinetics of amoxicillin trihydrate in cultured olive flounder (Paralichthys olivaceus)

The study was aimed at investigating the pharmacokinetics of amoxicillin trihydrate (AMOX) in olive flounder (Paralichthys olivaceus) following oral, intramuscular, and intravenous administration, using high‐performance liquid chromatography following. The maximum plasma concentration (C_max), following oral administration of 40 and 80 mg/kg body weight (b.w.), AMOX was 1.14 (T_max, 1.7 h) and 0.76 μg/mL (T_max, 1.6 h), respectively. Intramuscular administration of 30 and 60 mg/kg of AMOX resulted in C_max values of 4 and 4.3 μg/mL, respectively, with the corresponding T_max values of 29 and 38 h. Intravenous administration of 6 mg/kg AMOX resulted in a C_max of 9 μg/mL 2 h after administration. Following oral administration of 40 and 80 mg/kg AMOX, area under the curve (AUC) values were 52.257 and 41.219 μg/mL·h, respectively. Intramuscular 30 and 60 mg/kg doses resulted in AUC values of 370.274 and 453.655 μg/mL·h, respectively, while the AUC following intravenous administration was 86.274 μg/mL·h. AMOX bioavailability was calculated to be 9% and 3.6% following oral administration of 40 and 80 mg/kg, respectively, and the corresponding values following intramuscular administration were 86% and 53%. In conclusion, this study demonstrated high bioavailability of AMOX following oral administration in olive flounder.     

Pharmacokinetics and urinary excretion of sulphadimidine in sheep and goats

Pharmacokinetics and urinary excretion of sulphadimidine were determined in sheep and goats following a single intravenous injection (100 mg/kg). The disposition of the drug was described in terms of exponential expression: C _p= Be ^-βt. Based on total (free and bound) sulphonamide level in plasma, pseudo-distribution equilibrium was rapidly attained and the half-life for elimination was 3.88 ± 0.64 h and 4.00 ± 0.34 h in sheep and goats, respectively. Body clearance, which is the sum of all clearance processes was 88 ± 19 and 55 ± 4 ml/kg/h in sheep and goats. Based on this study a satisfactory intravenous dosage regimen might consist of 100 and 60 mg sulphadimidine/kg body wt for sheep and goats and should be repeated at 12 h intervals. The influence of disease conditions on predicted plasma levels remain to be verified experimentally. Three-quarters of an intravenously injected dose of sulphadimidine was excreted in the urine of sheep and goats within 24 h of administration. The drug was mainly excreted as free amine while acetylated drug constituted 7 and 8% of total drug content in the urine of sheep and goats, respectively.     

Pharmacokinetics of ceftiofur in llamas and alpacas

Pharmacokinetic studies of antibiotics in South American camelids are uncommon, therefore drugs are often administered to llamas and alpacas based on dosages established in other domestic species. The disposition of ceftiofur sodium was studied in llamas following intramuscular administration and in alpacas following intravenous and intramuscular administration. Eleven adult llamas were given ceftiofur sodium by intramuscular injection. Each animal received either a standard dose of 2.2 mg/kg or an allometrically scaled dose ranging from 2.62 to 2.99 mg/kg in a crossover design. Ten adult alpacas were given ceftiofur sodium by intravenous and intramuscular injections. Each animal received a standard dosage of 1 mg/kg or an allometrically scaled dose ranging from 1.27 to 1.44 mg/kg i.v., and 1.31-1.51 mg/kg i.m. Blood samples were collected at 0, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 36, 48, and 72 h after administration of the ceftiofur. Pharmacokinetic parameters of ceftiofur in llamas and alpacas were similar following i.m. dosing at both dose levels. The only differences noted were in the total AUC between dose levels, but the AUC/dose values were not different. A sequence effect was noted in the alpaca data, which resulted in lower AUCs for the second dose when the i.v. dose was given first, and with higher AUCs for the second dose when the i.m. dose was given first. Overall, ceftiofur pharmacokinetics in llamas and alpacas are similar, and also very similar to reported parameters for sheep and goats.     

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.     

Florfenicol pharmacokinetics in lactating cows after intravenous, intramuscular and intramammary administration

Pharmacokinetics of florfenicol 30% injectable solution was determined in lactating cows after intravenous, intramammary and intramuscular administration. Serum concentration-time data generated in the present study were analysed by non-compartmental methods based on statistical moment theory. Florfenicol half-life was 176 min, mean residence time 129 min, volume of distribution at steady-state 0.35 L/kg, and total body clearance 2.7 mL/min·kg after intravenous administration at 20 mg/kg. The absorption after intramuscular administration appeared slow and the kinetic parameters and the serum concentration vs. time curve were characteristic of absorption rate-dependent elimination. The absorption after intramammary administration of florfenicol at 20 mg/kg was good (53.9%) and resulted in serum concentrations with apparent clinical significance. The intramammary administration resulted in serum florfenicol concentrations that were significantly higher than the respective serum concentrations following Intravenous administration 4 h after administration and thereafter. Florfenicol absorption was faster from the mammary gland than from the muscle. The maximum serum concentrations ( C _max) were 6.9 μg/mL at 360 min after intramammary administration and 2.3 μg/mL at 180 min after intramuscular administration. The bioavailability of florfenicol was 54% and 38% after intramammary and intramuscular administration, respectively. The C _max in milk was 5.4 μg/mL at 180 min after intravenous and 1.6 μg/mL at 600 min after intramuscular administration.     

Pharmacokinetics of butafosfan after intravenous and intramuscular administration in piglets

The pharmacokinetics and bioavailability of butafosfan in piglets were investigated following intravenous and intramuscular administration at a single dose of 10 mg/kg body weight. Plasma concentration–time data and relevant parameters were best described by noncompartmental analysis after intravenous and intramuscular injection. The data were analyzed through WinNolin 6.3 software. After intravenous administration, the mean pharmacokinetic parameters were determined as T_1/2λz of 3.30 h, Cl of 0.16 L kg/h, AUC of 64.49 ± 15.07 μg h/mL, V_ss of 0.81 ± 0.44/kg, and MRT of 1.51 ± 0.27 h. Following intramuscular administration, the C_max (28.11 μg/mL) was achieved at T_max (0.31 h) with an absolute availability of 74.69%. Other major parameters including AUC and MRT were 48.29 ± 21.67 μg h/mL and 1.74 ± 0.29 h, respectively.     

Pharmacokinetics, bioavailability and dosage regimen of sulphadiazine (SDZ) in camels (Camelus dromedarius)

The pharmacokinetics of sulphadiazine (SDZ) (100 mg/kg, body weight) were investigated in six camels ( Camelus dromedarius ) after intravenous (i.v.) and oral (p.o.) administration. Following i.v. administration, the overall elimination rate constant (β) was 0.029±0.001/h and the half-life ( t _½β) was 23.14±1.06 h. The apparent volume of distribution ( V d_(area)) was 0.790±0.075 L/kg and the total body clearance ( Cl _B) was 23.29±2.50 mL/h/kg. After p.o. administration, SDZ reached a peak plasma concentration ( C _max(cal.)) of 62.93±2.79 μg/mL at a post injection time of ( T _max(cal.)) 22.98±0.83 h. The elimination half-life was 19.79±1.22 h, not significantly different from that obtained by the i.v. route. The mean absorption rate constant (K_a) was 0.056±0.002 h⁻¹ and the mean absorption half-life ( t _½Ka) was 12.33±0.37 h. The mean availability ( F ) of sulphadiazine was 88.2±6.2%.
  To achieve and maintain therapeutically satisfactory plasma SDZ levels of 50 μg/mL, the priming and maintenance doses would be 80 mg/kg and 40 mg/kg intravenously and 90 mg/kg and 45 mg/kg orally, respectively, to be repeated at 24 h intervals.     

Pharmacokinetics of kanamycin in dogs

The pharmacokinetics of kanamycin were studied in beagle dogs. A parenteral preparation of kanamycin sulphate (5% aqueous solution), which was given at a dosage level of 10 mg/kg of body weight, was the drug product used. The disposition curve which resulted from the intravenous administration of a single bolus dose of the drug was completely described by the biexponential equation:
C _p= 50e^{-0.1977 t} + 36.3e^{-0.0128 t} where C _p represents concentration of the drug in the serum at time t (in minutes) and the experimental constants are mean values. Pseudo-distribution equilibrium was rapidly attained and the apparent volumes of the central and peripheral compartments of the two-compartment open model were the same ( ca 125 ml/kg). Body clearance (mean ± S.D., n = 6) of kanamycin was 3.21 ±0.72 ml/kg/min. The half-life of the drug was short (58.18 ± 18.43 min) and independent of the route of parenteral (intravenous and intramuscular) administration. Absorption of kanamycin from the intramuscular site was rapid, with a half-time of 9.08 ± 1.10 min. A systemic availability of 89.1 ± 15.8% was obtained. Based on the bioavailability and disposition kinetics a dosage regimen consisting of the intramuscular injection of the dose (10 mg/kg) at 6 h intervals is proposed. An intravenous infusion rate of 48 μg/kgymin is predicted to establish a steady state serum concentration of 15 μg/ml, which is a therapeutic level of the antibiotic for susceptible micro-organisms.     

Pharmacokinetics of oxytetracycline in the red pacu (Colossoma brachypomum) following different routes of administration

Oxytetracycline (OTC) pharmacokinetics were studied in the red pacu ( Colossoma brachypomum ) following intravenous (i.v.) and intramuscular (i.m.) administration at a dose of 5 mg/kg body weight. OTC plasma concentrations were determined by high-performance-liquid-chromatography (HPLC). A non-compartmental model was used to describe plasma drug disposition after OTC administration. Following i.m. administration, the elimination half-life ( t _½) was 62.65 ± 1.25 h and the bioavailability was 49.80 ± 0.01%. After i.v. administration the t _½ was 50.97 ± 2.99 h, the V d was 534.11 ± 38.58 mL/kg, and CI _b was 0.121 ± 0.003 mL/min.kg. The 5 mg/kg i.v. dose used in this experiment resulted in up to 48 h plasma concentrations of OTC above the reported MIC values for some strains of fish pathogens such as Aeromonas hydrophila , A. liquefaciens , A. salmonicida , Cytophaga columnaris , Edwardsiella ictaluri , Vibrio anguillarium , V. ordalii , V. salmonicida and Yeersinia ruckeri . These MIC values are below the susceptible range (4 μg/mL) listed by the National Committee for Clinical Laboratory Standards (NCCLS) as determined by the NCCLS susceptibility interpretive criteria.