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.

Comparative disposition of tripelennamine in horses and camels after intravenous administration.

The pharmacokinetics of tripelennamine (T) was compared in horses (n = 6) and camels (n = 5) following intravenous (i.v.) administration of a dose of 0.5 mg/kg body weight. Furthermore, the metabolism and urinary detection time was studied in camels. The data obtained (median and range in brackets) in camels and horses, respectively, were as follows: the terminal elimination half-lives were 2.39 (1.91-6.54) and 2.08 (1.31-5.65) h, total body clearances were 0.97 (0.82-1.42) and 0.84 (0.64-1.17)L/h/kg. The volumes of distribution at steady state were 2.87 (1.59-6.67) and 1.69 (1.18-3.50) L/kg, the volumes of the central compartment of the two compartment pharmacokinetic model were 1.75 (0.68-2.27) and 1.06 (0.91-2.20) L/kg. There was no significant difference (Mann-Whitney) in any parameter between camels and horses. The extent of protein binding (mean +/- SEM) 73.6 + 8.5 and 83.4 +/- 3.6% for horses and camels, respectively, was not significantly statistically different (t-test). Three metabolites of T were identified in urine samples of camels. The first one resulted from N-depyridination of T, with a molecular ion of m/z 178, and was exclusively eliminated in conjugate form. This metabolite was not detected after 6 h of T administration. The second metabolite, resulted from pyridine ring hydroxylation, had a molecular ion of m/z 271, and was also exclusively eliminated in conjugate form. This metabolite could be detected in urine sample for up to 12 h after T administration. The third metabolite has a suspected molecular ion of m/z 285, was eliminated exclusively in conjugate form and could be detected for up to 24 h following T administration. T itself could be detected for up to 27 h after i.v. administration, with about 90% of eliminated T being in the conjugated form.

The pharmacokinetics, metabolism and urinary detection time of caffeine in camels.

The pharmacokinetics of caffeine were determined in 10 camels after an intravenous dose of 2.35 mg kg(-1). The data obtained (median and range) were as follows. The elimination half-life (t(1/2)) was 31.4 (21.2 to 58.9) hours, the steady state volume of distribution (V(SS)) was 0.62 (0.51 to 0.74) litre kg(-1)and the total body clearance (Cl(T)) was 14.7 (8.70 to 19.7) ml kg(-1)per hour. Renal clearance estimated in two camels was 0.62 and 0.34 ml kg(-1)per hour. In vitro plasma protein binding (mean +/-SEM, n = 10) to a concentration of 2 and 8 microg ml(-1)was 36.0 +/- 0.24 and 39.2 +/- 0.36 per cent respectively. Theophylline and theobromine were identified as caffeine metabolites in serum and urine. The terminal elimination half-life of the former, estimated in two camels, was 70. 4 and 124.4 hours. Caffeine could be detected in the urine for 14 days.

Identification and confirmation of 3-hydroxy metabolite of ketoprofen in camels by gas chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy.

The metabolites of ketoprofen were investigated in five camels following intravenous administration of a dose of 2.0 mg/kg body weight. Two metabolites were identified. The first one was purified with thin-layer chromatography. It was identified by gas chromatography-mass spectrometry (GC-MS) in comparison with authenticated reference standard and was found to be hydroxyketoprofen due to reduction of the ketone group of ketoprofen. The second metabolite was purified by high-performance liquid chromatography. It was identified with GC-MS and nuclear magnetic resonance spectroscopy as 3-hydroxybenzolketoprofen resulting from oxidation of the aromatic ring.

The disposition of theophylline in camels after intravenous administration.

The pharmacokinetics of theophylline were determined after an intravenous (i.v.) dose of 2.36 mg/kg in six camels and 4.72 mg/kg body weight in three camels. The data obtained (median and range) for the low and high dose, respectively, were as follows: the distribution half-lives (t1/2 alpha) were 1.37 (0.64-3.25) and 2.66 (0.83-3.5) h, the elimination half-lives (t1/2 beta) were 11.8 (8.25-14.9) and 10.4 (10.0-13.5) h, the steady state volumes of distribution (Vss) were 0.88 (0.62-1.54) and 0.76 (0.63-0.76) L/kg, volumes of the central compartment (Vc) were 0.41 (0.35-0.63) and 0.51 (0.36-0.52) L/kg, total body clearances (Clt) were 62.3 (39.4-97.0) and 50.2 (47.7-67.4) mL/h.kg body weight and renal clearance (Vr) for the low dose was 0.6 (0.42-0.96) mL/h.kg body weight. There was no significant difference in the pharmacokinetic parameters between the two doses. Theophylline protein binding at a concentration of 5 micrograms/mL was 32.2 +/- 3.3%. Caffeine was identified as a theophylline metabolite but its concentration in serum and urine was small. Based on the pharmacokinetic values obtained in this study, a dosage of 7.5 mg/kg body weight administered by i.v. injection at 12 h intervals can be recommended. This dosing regimen should achieve an average steady state serum concentration of 10 micrograms/mL with peak serum concentration not exceeding 15 micrograms/mL.

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 tolfenamic acid and its detection time in urine after intravenous administration of the drug in camels (Camelus dromedarius).

OBJECTIVE: To document tolfenamic acid disposition variables, identify its major phase-1 metabolite and fragmentation pattern, and establish detection time in urine after single IV bolus administration to make recommendations on avoiding violative residues in racing camels. ANIMALS: 7 healthy camels (6 males, 1 female), 8 to 11 years old and weighing from 300 to 480 kg. PROCEDURE: Blood samples were collected at 0, 5, 10, 15, 30, 45, and 60 minutes and at 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 13, 14, 15, and 16 hours after IV administration of tolfenamic acid (2.0 mg/kg of body weight). Urine samples were collected daily for 14 days after drug administration. Serum tolfenamic acid concentration was measured; limit of quantification was 50 ng/ml. A metabolite of tolfenamic acid in urine was isolated and identified, and its major fragmentation pattern was verified. Screening for tolfenamic acid and its metabolite in urine was performed. RESULTS: Mean +/- SEM tolfenamic acid elimination half-life was 5.76+/-0.26 hours. Total body clearance was 0.109+/-0.011 L/kg/h, and steady-state volume of distribution was 0.68+/-0.06 L/kg. Detection time for tolfenamic acid and its hydroxylated metabolite in urine after IV administration of a dose of 2.0 mg/kg was 5 and 7 days, respectively. CONCLUSIONS: Camels eliminate tolfenamic acid mainly via metabolism more slowly than do cattle. The extrapolated dose regimen from cattle to camels appears inappropriate. Veterinarians are advised not to use tolfenamic acid in camels for at least 8 days prior to racing.

Identification of a flunixin metabolite in camel by gas chromatography-mass spectrometry.

A flunixin metabolite, a hydroxylated product, has been identified in camel urine and plasma samples using gas chromatography-mass spectrometry (GC-MS) and GC-MS-MS in the electron impact and chemical ionization modes. Its major fragmentation pattern has been verified by GC-MS-MS in daughter ion and parent ion scan modes. The method could detect flunixin and its metabolite in camel urine after a single intravenous dose of 2.2 mg of flunixin/kg body weight for 96 and 48 h, respectively, which increases the reliability of antidoping control analysis.

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 (t1/2 beta) were 3.76 +/- 0.24 and 4.08 +/- 0.49 h, the steady state volumes of distribution (Vdss) were 320.61 +/- 38.53 and 348.84 +/- 35.36 mL/kg body weight, total body clearances (ClT) were 88.96 +/- 6.63 and 84.86 +/- 4.95 mL/h/kg body weight and renal clearances (Clr) 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.