Pharmacokinetics and Dosage Regimen of Ceftriaxone in Buffalo Calves

The pharmacokinetics and dosage regimen of ceftriaxone were investigated in buffalo calves (n = 6) following a single intravenous administration of ceftriaxone (10 mg/kg). The elimination rate constant was 0.18 +/- 0.01 h(-1) and the elimination half-life was 3.79 +/- 0.09 h. The apparent volume of distribution (Vd(area)) was 1.40 +/- 0.01 L/kg and the total plasma clearance was 0.26 +/- 0.01 L/(kg h). Approximately 43% of total administered dose of ceftriaxone was excreted in urine within 8 h. To maintain a minimum therapeutic concentration of 1 microg/ml, a satisfactory intravenous dosage regimen of ceftriaxone in buffalo calves is 13 mg/kg repeated at 12 h intervals.     

Disposition kinetics and dosage of cephaloridine in calves

The disposition kinetics and dosage regimen of cephaloridine were investigated in calves following a single intravenous dose of 10 mg.kg-1. The distribution half-life and elimination half-life were 0.16 +/- 0.02 and 1.96 +/- 0.16 h, respectively. The apparent volume of distribution was 0.64 +/- 0.06 l.kg-1 and total body clearance which represents the sum of all clearance processes, was 225.2 +/- 15.1 ml.kg-1.h-1. Based on kinetic parameters, a satisfactory intravenous dosage regimen of cephaloridine in calves would be 11.0 mg.kg-1 repeated every 8 h.     

The kinetic disposition and dosage regimen for carbenicillin in buffalo calves

The distribution half-life, elimination half-life, apparent volume of distribution and total body clearance of carbenicillin in healthy buffalo calves following a single intravenous administration (50 mg/kg) were 0.057±0.005 h, 1.688±0.11 h, 0.185±0.021 L kg^-1 and 75.97±6.519 ml kg^-1 h^-1 respectively. A satisfactory dosage regimen for carbenicillin in buffalo calves was calculated to be 56 mg/kg followed by 52 mg/kg body weight repeated at 6 h intervals.     

Pharmacokinetics and urinary excretion of gentamicin in Bubalus bubalis calves following intramuscular administration

The pharmacokinetics and urinary excretion of gentamicin was studied in buffalo calves after a single intramuscular administration (10 mg kg-1). Kinetic determinants were calculated by using a two compartment open model. The absorption (t1/2Ka) and biological half lives (t1/2 beta) were calculated to be 0.43 +/- 0.08 and 3.79 +/- 0.23 h, respectively. The value of the apparent volume of distribution (VdB) was found to be 0.38 +/- 0.07 litre kg-1. The satisfactory intramuscular dosage regimen of gentamicin for buffalo calves would be 3.23 mg kg-1 as priming dose and 2.88 mg kg-1 as maintenance dose to be repeated at 12 hour intervals to achieve and maintain the therapeutic plasma levels within safe limits. Urinary excretion of gentamicin was very rapid during the first 12 hours as 48.07 +/- 1.39 per cent of the total administered dose was excreted unchanged during this period.     

Disposition kinetics and dosage regimen of ceftriaxone in crossbred calves (short communication).

Disposition kinetics and urinary excretion of ceftriaxone were investigated in healthy crossbred calves after its single intravenous administration (10 mg kg-1). Based on kinetic parameters, an appropriate dosage regimen of ceftriaxone in calves was calculated. The peak plasma level of ceftriaxone at 1 min was 84.0 +/- 1.55 micrograms ml-1 which declined to 0.43 +/- 0.05 microgram ml-1 at 8 h. The value of elimination half-life (t1/2 beta), volume of distribution Vd (area) and total body clearance (ClB) were 4.39 +/- 0.63 h, 1.91 +/- 0.19 L kg-1 and 0.31 +/- 0.01 L kg-1 h-1, respectively. Approximately 41 per cent of total administered drug was recovered in the urine within 24 h of its administration. The plasma protein binding of ceftriaxone was found to be concentration dependent with an overall mean of 38.55 per cent. The binding capacity of ceftriaxone to plasma proteins and the dissociation rate constant of protein-drug complex were 20.1 x 10(-8) +/- 18.4 x 10(-8) mole g-1 and 1.07 x 10(-6) +/- 0.52 x 10(-6) mole, respectively. An appropriate intravenous dosage regimen of ceftriaxone in cattle would be 12 mg kg-1 repeated at 24 h.     

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.     

Pharmacokinetics and Dosage Regimen of Enrofloxacin in Buffalo Bulls after Intramuscular Administration

The disposition kinetics and dosage regimen of enrofloxacin were investigated in breeding buffalo bulls following a single intramuscular administration of 5 mg/kg. The absorption half-life, half-life of the terminal phase, apparent volume of distribution and total body clearance were 0.262±0.099 h, 1.97±0.23 h, 0.61±0.13 L/kg and 210.2±18.6 ml/(kg.h), respectively. Therapeutic plasma levels (1 g/ml) were maintained for up to 6 h. A satisfactory intramuscular dosage regimen for enrofloxacin in buffalo bulls would be 8.5 mg/kg followed by 8.0 mg/kg at 8 h intervals.     

Subcutaneous pharmacokinetics and dosage regimen of cefotaxime in buffalo calves (Bubalus bubalis)

The pharmacokinetics and dosage regimen of cefotaxime following its single subcutaneous administration (10 mg/kg) were investigated in buffalo calves. Plasma and urine samples were collected over 10 and 24 h post administration, respectively. Cefotaxime in plasma and urine was estimated by microbiological assay technique using E. coli as test organism. The pharmacokinetic profiles fitted one-compartment open model. The peak plasma levels of cefotaxime were 6.48 ± 0.52 µg/ml at 30 min and the drug was detected upto 10 h. The absorption half-life and elimination half-life were 0.173 ± 0.033 h and 1.77 ± 0.02 h, respectively. The apparent volume of distribution and total body clearance were 1.17 ± 0.10 l/kg and 0.45 ± 0.03 l/kg/h, respectively. The urinary excretion of cefotaxime in 24 h, was 5.36 ± 1.19 percent of total administrated dose. A satisfactory subcutaneous dosage regimen for cefotaxime in buffalo calves would be 13 mg/kg repeated at 12 h intervals.     

Intramuscular Kinetics and Dosage Regimens for Pralidoxime in Buffalo Calves (Bubalus bubalis)

The plasma levels, disposition kinetics and a dosage regimen for pralidoxime (2-PAM) were investigated in male buffalo calves following single intramuscular administration (15 or 30 mg/kg). The effects of 2-PAM on various blood enzymes were also determined. The absorption half-life, elimination half-life, apparent volume of distribution and total body clearance of 2-PAM were 1.08±0.19 h, 3.14–3.19 h, 0.83–1.01 L/kg and 184.9–252.1 ml/(kg h), respectively. At doses of 15 and 30 mg/kg body weight, a plasma concentration 4 g/ml was maintained for up to 4 and 6 h, respectively. Pralidoxime significantly lowered the serum level of transferases, phosphatases and lactate dehydrogenase but did not influence the acetylcholinesterase and carboxylesterase enzymes. The most appropriate dosage regimen for 2-PAM in the treatment of organophosphate toxicity in buffaloes would be 25 mg/kg followed by 22 mg/kg at 8 h intervals.     

Pharmacokinetics, urinary excretion and dosage regimen of diminazene in crossbred calves

The pharmacokinetics, urinary excretion and dosage regimen of diminazene were investigated in crossbred male calves following a single intramuscular dose (3.5 mg x kg-1). Following intramuscular administration, the pharmacokinetics of diminazene was described with a one-compartment open model. The absorption rate constant and absorption half-life were 9.86 +/- 3.06 h-1 and 0.121 +/- 0.40 h, respectively. The value of elimination half-life was 107.5 +/- 8.50 h. The apparent volume of distribution was 0.74 +/- 0.07 L x kg-1. Systemic availability following intramuscular administration was 91.7%. Approximately 65% of the administered dose of diminazene was eliminated in the urine within 24 h of its intramuscular administration. Diminazene was bound to plasma proteins to the extent of approximately 32%. The satisfactory intramuscular dosage regimen of diminazene for calves would be 2.24 mg x kg-1 followed by 1.5 mg x kg-1 at 7 days.     

Pharmacokinetics and dosage regimen of 2-pyridine aldoxime in Bubalus bubalis intoxicated with fenitrothion

In the present study, the pharmacokinetics of 2-pyridine aldoxime (2-PAM, 30 mg/kg, i.v.) alone and in conjunction with atropine (0.3 mg/kg; 1/4 i.v., 3/4 i.m.) was investigated in 10 Bubalus bubalis intoxicated with a single oral lethal dose of fenitrothion (435 mg/kg). Based on the kinetic parameters, an appropriate dosage regimen of 2-PAM in B. bubalis was calculated. There was no significant difference between plasma levels and pharmacokinetic parameters of 2-PAM in the two groups of animals, given 2-PAM alone and in conjunction with atropine. The peak plasma concentration of 2-PAM at 1 min was in the range of 189.5-196.6 microg/mL which declined to 9.22-9.98 microg/mL at 4 h. The values of elimination half-life, Vd(area) and total body clearance were 2.41-2.67 h, 0.77-0.95 L/kg and 227.5-245.7 mL/kg/h, respectively. The binding capacity of 2-PAM to plasma proteins of fenitrothion-intoxicated buffalo calves and dissociation rate constant of protein drug complex were 0.015 x 10(-6) mol/g and 2.367 x 10(-6) mol, respectively. Approximately 63% of 2-PAM was bound with plasma proteins. In the treatment of organophosphate insecticide (OPI) toxicity in B. bubalis, an appropriate i.v. dosage regimen of 2-PAM in conjunction with atropine would be 18 mg/kg followed by 15 mg/kg at 4 h interval.     

Pharmacokinetics of marbofloxacin in horses

Marbofloxacin is a fluoroquinolone antibiotic expected to be effective in the treatment of infections involving gram-negative and some gram-positive bacteria in horses. In order to design a rational dosage regimen for the substance in horses, the pharmacokinetic properties of marbofloxacin were investigated in 6 horses after i.v., subcutaneous and oral administration of a single dose of 2 mg/kg bwt and the minimal inhibitory concentrations (MIC) assessed for bacteria isolated from equine infectious pathologies. The clearance of marbofloxacin was mean +/- s.d. 0.25 +/- 0.05 l/kg/h and the terminal half-life 756 +/- 1.99 h. The marbofloxacin absolute bioavailabilities after subcutaneous and oral administration were 98 +/- 11% and 62 +/- 8%, respectively. The MIC required to inhibit 90% of isolates (MIC90) was 0.027 microg/ml for enterobacteriaceae and 0.21 microg/ml for Staphylococcus aureus. The values of surrogate markers of antimicrobial efficacy (AUIC, Cmax/MIC ratio, time above MIC90) were calculated and the marbofloxacin concentration profiles simulated for repeated administrations. These data were used to determine rational dosage regimens for target bacteria. Considering the breakpoint values of efficacy indices for fluoroquinolones, a marbofloxacin dosage regimen of 2 mg/kg bwt/24 h by i.v., subcutaneous or oral routes was more appropriate for enterobacteriaceae than for S. aureus.     

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.     

Pharmacokinetics and intramuscular bioavailability of difloxacin in dromedary camels (Camelus dromedarius)

Single-dose disposition kinetics of difloxacin (5mg/kg bodyweight) were determined in clinically normal male dromedary camels (n=6) following intravenous (IV) and intramuscular (IM) administration. Difloxacin concentrations were determined by high performance liquid chromatography with fluorescence detection. The concentration-time data were analysed by compartmental and non-compartmental kinetic methods. Following a single IV injection, the plasma difloxacin concentration-time curve was best described by a two-compartment open model, with a distribution half-life (t(1/2alpha)) of 0.22+/-0.02h and an elimination half-life (t(1/2beta)) of 2.97+/-0.31h. Steady-state volume of distribution (V(dss)) and total body clearance (Cl(tot)) were 1.02+/-0.21L/kg and 0.24+/-0.07L/kg/h, respectively. Following IM administration, the absorption half-life (t(1)(/)(2ab)) and the mean absorption time (MAT) were 0.44+/-0.03h and 1.53+/-0.22h, respectively. The peak plasma concentration (C(max)) of 2.84+/-0.34microg/mL was achieved at 1.42+/-0.21h. The elimination half-life (t(1/2el)) and the mean residence time (MRT) was 3.46+/-0.42h and 5.61+/-0.23h, respectively. The in vitro plasma protein binding of difloxacin ranged from 28-43% and the absolute bioavailability following IM administration was 93.51+/-11.63%. Difloxacin could be useful for the treatment of bacterial infections in camels that are sensitive to this drug.     

The Disposition Kinetics,Urinary Excretion and Dosage Regimen of Ciprofloxacin in Buffalo Calves (Bubalus bubalis)

The disposition kinetics, urinary excretion and a dosage regimen for ciprofloxacin after a single intravenous administration of 5 mg/kg was investigated in 5 healthy buffalo calves. The disposition kinetics were best fitted to a three-compartment open model. After 1 min, the concentration of ciprofloxacin in plasma was 8.50±0.39 g/ml and the minimum therapeutic concentration was maintained for 10 h. The elimination half-life and volume of distribution were 3.88 and 0.08 h and 3.97±0.22 L/kg, respectively. The total body clearance and T/P ratio were 0.709±0.025 L/kg per h and 6.13±0.54, respectively. Approximately 28.3% of the total administered dose of ciprofloxacin was recovered in urine within 24 h of administration. To maintain a minimum therapeutic plasma concentration of 0.10 g/ml, a satisfactory intravenous dosage regimen of ciprofloxacin, computed on the basis of disposition kinetic data obtained in healthy buffalo calves, would be 3 mg/kg repeated at 12 h intervals.     

Pharmacokinetics and intramuscular bioavailability of amikacin in chickens following single and multiple dosing

The pharmacokinetics of amikacin were studied in healthy mature female chickens (n = 6). Single doses of amikacin were injected as an i.v. bolus (10 mg/kg) and i.m. (20 mg/kg) into the same birds with a 30-day rest period between treatments. Amikacin was determined by the fluorescence polarization immunoassay method. The i.v. pharmacokinetics could be described by a two-compartment model with a t1/2 alpha of 0.150 +/- 0.064 h and a t1/2 beta of 1.44 +/- 0.34 h. The total body clearance was 0.109 +/- 0.017 1/h/kg and the volume of distribution at steady-state was 0.193 +/- 0.060 l/kg. Following a single i.m. injection, the peak plasma concentration (Cmax) was 50.79 +/- 4.05 micrograms/ml and occurred at 0.50 +/- 0.26 h. The i.m. extent of absorption was 91.2 +/- 17.6%. Simultaneous modeling of i.v. and i.m. results provided estimates of an absorption half-life of 0.480 +/- 0.158 h. The i.m. pharmacokinetics after repeated administration were studied following the tenth dose (20 mg/kg, every 8 h). The Cssmax was 38.58 +/- 6.96 micrograms/ml and occurred at 0.79 +/- 0.37 h, and the biological half-life of amikacin was 1.86 +/- 0.47 h. The multiple dosing yielded peak concentrations of 39 micrograms/ml and trough concentrations of 3.26 micrograms/ml. Based on these data, the recommended amikacin dosage in chickens is 20 mg/kg body weight every 8 h.     

The pharmacokinetics of promethazine after intravenous administration in camels

The pharmacokinetics of promethazine were determined in seven camels (Camelus dromedarius) after an intravenous dose of 0.5 mg kg body weight.-1 The data obtained (median and range) were as follows: the elimination half-life (t1/2 beta) was 5.62 (2.84-6.51) h; the steady state volume of distribution (Vdss) was 8.90 (7.10-12.00) L kg-1, total body clearance (CT) was 24.5 (17.22-33.65) ml kg-1 min-1 and renal clearance (Clr) was 4.81 (1.97-5.48) ml kg-1 min-1.     

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.     

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.     

Pharmacokinetics of oxytetracycline hydrochloride in rabbits

Pharmacokinetics of oxytetracycline HCl (OTC) was studied in rabbits. After 10 mg of OTC/kg of body weight was administered IV, the distribution half-life was 0.06 hour, terminal half-life was 1.32 hours, volume of distribution area was 0.861 L/kg, and total body clearance was 0.434 L/kg/h. After 10 mg of OTC/kg was given IM, the absorption half-life was 2.09 hours, extent of absorption was 71.4%, and total body clearance of the absorbed fraction was 0.576 L/kg/h. Based on these kinetic data, a dosage of 15 mg of OTC/kg, every 8 hours was developed. This dose given IM for 7 consecutive days resulted in observed steady-state maximum and minimum concentrations (mean +/- SD) of 4.7 +/- 0.3 micrograms/ml and 3.2 +/- 0.6 micrograms/ml, respectively. Twice this dose (30 mg of OTC/kg, every 8 hours) given IM caused anorexia and diarrhea.