Disposition and urinary excretion of phenylbutazone in normal and febrile greyhounds

Five days after the induction of acute systemic inflammation in greyhounds by intramuscular and subcutaneous injections of Freund's adjuvant, the hepatic concentrations of cytochromes P-450 and b₅, the activities of the hepatic microsomal enzymes aniline p-hydroxylase and aminopyrine n-demethylase and the disposition and urinary excretion of phenylbutazone were determined. The mean plasma concentrations of phenylbutazone after intravenous administration were described by the bi-exponential equations: Cp = 144·2e^−34·6t + 171·5e^−0·104t for five normal greyhounds and Cp = 113·6e^−16·13t + 163·1e^−0·108t for five febrile greyhounds. The elimination half-lives, total body clearances and apparent volumes of distribution were 6·7 hours, 18·4 ml kg⁻¹ hour⁻¹ and 0·18 litre kg⁻¹, for the normal greyhounds, and 6·4 hours, 19·5 ml kg⁻¹ hour⁻¹ and 0·18 litre kg⁻¹, for the febrile greyhounds. There were no significant differences between the pharmacokinetic parameters describing the distribution and elimination of phenylbutazone, or between the quantities of phenylbutazone, oxyphenbutazone and hydroxyphenylbutazone excreted in the urine. In the febrile greyhounds, there were significant decreases in the hepatic microsomal concentrations of cytochromes P-450 and b₅ and in the activities of aniline p-hydroxylase and aminopyrine n-demethylase.     

Effect of chronic hypocortisolaemia on plasma cortisol concentrations during intravenous infusions of hydrocortisone sodium succinate in dogs

Intravenous infusions of hydrocortisone sodium succinate (HSS) were given at 0·625 mg kg⁻¹ hour⁻¹ and 0·312 mg kg⁻¹ hour⁻¹ to six dogs. Plasma cortisol concentrations were measured by radioimmunoassay at 0, 15, 30, 45 and 60 minutes and then every 30 minutes for a further five hours. Chronic hypocortisolaemia was induced and maintained with mitotane and the HSS infusions were repeated after 31 and 50 days. No statistically significant difference was observed in the plasma cortisol concentrations after either period of hypocortisolaemia, but the plasma cortisol concentrations tended to be higher in most of the dogs.     

Effect of dietary chloride content on the elimination of bromide by dogs

The effect of dietary chloride content (0·2, 0·4 and 1·3 per cent chloride on a dry matter basis) on the disposition of a single oral dose of bromide (14 mg kg⁻¹ was evaluated in normal beagles. Increasing the dietary chloride content from 0·2 to 1·3 per cent resulted in a significant decrease in the mean apparent elimination half-life from 69 ± 22 days to 24 ± 7 days. The mean area under the concentration curve ( ) for dogs fed 1·3 per cent chloride was significantly smaller than the for dogs fed 0·2 per cent chloride. Dietary chloride had no effect on the maximum serum concentrations (C_max) or on the time (T_max) to reach the maximum concentrations. The steady-state serum bromide concentrations predicted from the single dose data for daily doses of 14 mg kg⁻¹ of bromide were significantly lower in dogs fed 1·3 per cent chloride (310 ± 150 mg litre⁻¹) than in dogs fed 0·2 per cent chloride (1950 ± 1140 mg litre⁻¹). The predicted mean daily doses of bromide necessary to maintain serum levels within the therapeutic range for dogs fed 1·3 per cent chloride (43 ± 13 mg kg⁻¹) were almost twice as high as the dose estimated for dogs fed 0·4 per cent chloride (22 ± 3 mg kg⁻¹) and nearly three times as high as the dose estimated for dogs fed 0·2 per cent chloride (15 ± 4 mg kg^−l). These differences were statistically significant (P=0·002).     

Epidermal and hepatic glucocorticoid receptors in cats and dogs

Low capacity, high affinity [³H] dexamethasone binding receptors were identified in cytosolic preparations of liver (mean number 45±10·1 fmol mg⁻¹ protein, apparent dissociation constant 0·4±0·1 nM) and skin (mean number 46·4±23·8 fmol mg⁻¹ protein, apparent dissociation constant 1 ± 0·2 nM) of clinically normal dogs. For clinically normal cats, approximately half these numbers of receptors with a lower affinity, were detected in liver (mean number 23·1±10·4 fmol mg⁻¹ protein, apparent dissociation constant 3·2±0·9 nM) and skin (mean number 23·90±10·9 fmol mg⁻¹ protein, apparent dissociation constant 2·2±1·5 nM). This difference between dogs and cats in [³H] dexamethasone binding receptors may contribute to the relative glucocorticoid resistance observed in cats.     

Comparison of carprofen and flunixin meglumine asadjunctive therapy in bovine respiratory disease

In an open, controlled, multi-centre clinical field trial, seven ‘naturally occurring’ outbreaks of acutefebrile (rectal temperature ≥ 39·5°C) respiratory disease in housed calves were treated with a single antimicrobial agent, and either the non-steroidal anti-inflammatory drug (NSAID) carprofen (n=95) or flunixin meghunine (n=92) on an alternate basis. Carprofen was administered as a single subcutaneous injection at a mean dosage of 1·4 mg kg⁻¹ (range 1·2 to 1·9 mg kg⁻¹) body weight on the first day and flunixin meglumine by intravenous injection at a mean dosage of 2·0 mg kg⁻¹ (range 1·2 to 2·6 mg kg⁻¹) body weight on the first 3 consecutive days. All calves were examined clinically immediately prior to initial treatment and on three occasions up to 1 week after the end of treatment. There were no statistically significant differences between NSAID groups in reduction of clinical parameters between examinations, or in overall efficacy. This trial demonstrated that a single dose of carprofen was equally effective as three daily closes of flunixin meglumine as adjunctive therapy to antimicrobial treatment in acute respiratory disease in calves.     

Penetration of amoxycillin to the respiratory tract tissues and secretions in Actinobacillus pleuropneumoniae infected pigs

The pharmokinetic properties of amoxycillin, and its penetration into respiratory tract tissue, were determined in 18 Actinobacillus pleuropneumoniae infected pigs, after a single i.v. dose of 8·6 mg amoxycillin kg⁻¹ bodyweight. Pleuropneumoniae was produced experimentally in pigs by an aerosol infection model. The infection created a homogenous response, characterised by depression of breathing and increased body temperature. The clinical symptoms were accompanied by increased haptoglobin levels and circulating white blood cell counts. At necropsy the findings were characterised by a bilateral fibrinous pleuropneumonia. Twenty hours after infection, the pigs were administered amoxycillin i.v. The plasma concentration-time curve was described by a three compartment open model. The mean residence time and the elimination half-life were l·5 and 3·4 hours, respectively. The steady-state volume of distribution was 0·67 litres kgl, and the clearance was 0·46 litres kg⁻¹ hour⁻¹. There were no significant differences between these values and those reported previously for healthy pigs. The concentration of amoxycillin in bronchial secretions, lung tissue and diseased lung tissue peaked two hours after intravenous drug administration, while amoxycillin concentration in pleural fluid, lymph nodes and tonsil tissue peaked at the first sampling point one hour after drug administration. The concentration of amoxycillin in secretions and tissue decreased by a slower rate than amoxycillin concentration in plasma, resulting in an increasing tissue-to-plasma concentration ratio. The distribution ratios (AUC_tissue/JAUC_plasma) was 0·53 for bronchial secretions, 0·44 for pneumonic lung tissue, 0·42 for lung tissue, 1·04 for pleural fluid, 0·58 for lymph nodes and 0·37 for tonsil tissue. The distribution of amoxycillin to secretions was increased compared with that previously reported for healthy pigs, while only minor changes were observed in lung tissue.     

Effects of inhibition of nitric oxide synthase on systemic arterial pressure and renal vascular resistance in cats

These studies were undertaken to examine the systemic and renal effects of the pharmacological inhibition of endothelium-derived nitric oxide (EDNO) in cats. In six healthy cats, the intravenous infusion of nitro-L-arginine at a dose of 100 μg kg⁻¹ bodyweight min⁻¹ resulted in a marked increase (P<0·001) in mean arterial pressure from the control value of 116·7 ± 4·6 mmHg to 154·2 ± 6·8 mmHg and an increase (P<0·05) in renal vascular resistance from the control value of 3·69 ± 0·33 mmHg min ml⁻¹ to 6·83 ± 1·15 mmHg min ml⁻¹. The increase in renal vascular resistance was generalised, with comparable increments in preglomerular and postglomerular vascular resistance. Mean values for glomerular capillary pressure (61·1 ± 61·9 vs 1·9 ± 1·6 mmHg), calculated from the sum of arterial colloid osmotic pressure plus proximal tubule stop-flow pressure, did not change in response to the infusion of nitro-L-arginine. However, there was a marked reduction in renal blood flow (29·4 ± 3·1 to 16·9 ± 2·3 ml min⁻¹, P<0·01) and glomerular filtration rate (5·22 ± 0·57 to 3·52 ± 0·45 ml min⁻¹, P<0·01). These results provide evidence that EDNO plays an important role in the basal regulation of systemic arterial blood pressure and renal haemodynamics in cats.     

Lincomycin and spectinomycin in the treatment of breeding rams with semen contaminated with ureaplasmas

Ureaplasma species were isolated from semen samples collected sequentially from one Awassi and three Assaf breeding rams. Each ram was injected subcutaneously with an aqueous solution of lincomycin and spectinomycin for five consecutive days at a dose equivalent to 4·5 mg kg⁻¹ lincomycin and 9·0 mg kg⁻¹ spectinomycin daily. Serum and semen samples were collected at intervals during the treatment and assayed for lincomycin. No Ureaplasma species were isolated from semen samples collected during the course of the treatment and at intervals for 17 days after the last treatment. The concentration of lincomycin in semen ranged from 0·51 μg ml⁻¹ four hours after treatment to 0·08 μg ml⁻¹ 24 hours after treatment, and these levels were three to nine times higher than the corresponding serum concentrations.     

Blood lactate disappearance after maximal exercise in trained and detrained horses

The influence of training on blood lactate concentrations during treadmill exercise and a 40-minute inactive recovery period was examined in seven trained and seven detrained thorough-bred horses. Lactate concentrations were measured in venous blood collected at the end of each exercise state, and at intervals for 40 minutes afterwards. Measurements were made of maximum oxygen uptake (V̇O_2max, ml kg⁻¹ min⁻¹), VLA4 (velocity at which blood lactate concentration was 4 mmol litre⁻¹); LA8 (lactate concentration [mmol litre⁻¹] during exercise at 8 m sec⁻¹), peak lactate (highest lactate concentration after exercise), LA40 (lactate concentration 40 minutes after exercise), the time of peak lactate concentration (minutes after exercise) and the rate of disappearance of blood lactate (Rt_d). The trained horses had a significantly lower LA8 (2·1 ± 0·1 vs 6·5 ± 1 mmol litre⁻¹, P<0·01), higher VLA4 (9·8 ± 0·2 vs 5·8 ± 0·6 m sec⁻¹, P<0·01) and higher V̇0_2max (156·3 ± 3·8 vs 107·1 ± 3·9 ml kg⁻¹ min⁻¹, P<0·001). The value of Rt_d and the time of peak lactate concentration were not significantly different.     

Effects of reducing dietary ([Na + K − [Cl + SO4]) on bone in dairy cows at parturition

The effects of feeding diets with different milliequivalents (mEq) of dietary ([Na⁺ + K⁺] − [Cl⁻ + SO₄⁼]) to dairy cows during the last seven weeks of pregnancy on bone morphology at parturition were studied. Nine monozygotic twin pairs of pregnant cows (five pairs of parity 1 or 2 and four pairs of parity 3 or more) were allocated to two diets which were formulated to provide either −4 mEq (anion diet) or +572·5 mEq (cation diet) of ([Na⁺ + K⁺] − [Cl⁻ + SO₄⁼]) kg⁻¹ dietary dry matter. Bone biopsies were taken from the tuber coxae between three and eight hours after parturition. The plasma concentrations of calcium and inorganic phosphorus, the total plasma alkaline phosphatase activity and the urinary hydroxyproline:creatinine ratio were not significantly affected by diet during the experimental period. In low parity (2 or less) cows the percentage trabecular bone volume, the percentage osteoclast surface and the mean number of osteoclasts per microscopic field (identified by Goldner staining) were lower on the anion diet than on the cation diet (P<0-02). In the high parity cows, the percentage osteoid volume (P<0·05) and the ratio of percentage osteoid volume to percentage osteoid surface (P<0·001) were greater in the cows fed the anion diet than in the cows fed the cation diet. The results show that reducing the mEq of dietary ([Na⁺ + K⁺] − [Cl⁻ + SO₄⁼]) to −4 mEq kg⁻¹ dietary dry matter affected some of the parameters of bone formation but did not enhance bone resorption.     

Comparison of the disposition of carbimazole and methimazole in clinically normal cats

The oral disposition of the antithyroid drugs methimazole and carbimazole were compared in nine clinically normal cats. After the administration of 5 mg of methimazole, serum concentrations of methimazole increased in all the cats, with mean drug concentrations reaching peak values (1·37 μg ml⁻¹) at 30 minutes. After administration of 5 mg carbimazole, serum concentrations of carbimazole remained low, but serum methnnazole became readily measurable, with mean drug concentrations reaching peak values (0·79 μg ml⁻¹) at 120 minutes. When serum concentrations of methimazole attained after administration of the two antithyroid drugs were compared, the mean maximum serum methimazole concentration achieved after administration of methimazole was approximately two-fold higher than peak concentrations measured after administration of carbimazole. In addition, the mean area under the serum concentration curve (AUC) after administration of methimazole was approximately two-fold higher than the mean AUC determined after administration of carbimazole. When the differences in molecular weight between the two drugs was taken into consideration, however, these methimazole:carbimazole ratios of 2:1 were nearly equivalent to the molar ratio of the 5 mg doses of the drugs given (1·63). Results of this study indicate that carbimazole is nearly totally converted to methimazole after oral administration to cats, similarly to the findings in man. The finding of less available serum methimazole after administration of a 5 mg tablet of carbimazole than after methimazole is also consistent with published antithyroid drug dosages needed to control hyperthyroidism in cats.     

Evaluation of free and liposome-encapsulated gentamycin for intramuscular sustained release in rabbits

Gentamycin sulphate ( ) and gentamycin oleate ( ) were encapsulated in liposomes composed of phosphatidylcholine ( ) and cholesterol ( ) (molar ratio 7:7:2 and 5:5:l, respectively), and were administered via intramuscular injection to rabbits, to evaluate their potential use as sustained release formulations. Five groups of five animals each were used for the pharmacokinetic study, and treatments were established as follows: 3 mg kg⁻¹ of i.v., 3 mg kg⁻¹ of i.m., 3 mg kg⁻¹ of liposome-containing gentamycin sulphate ( ) i.m., 3 mg kg⁻¹ of i.m., and 3 mg kg⁻¹ of liposome-containing gentamycin oleate ( ) i.m. Gentamycin plasma concentrations after i.m. administration of LGS were extremely low compared with those obtained after the i.m. administration of ; the peak plasma concentration ( _max) showed an eight-fold decrease with , and the area under the concentration-time curve ( ) was four-fold lower for the liposomal form. The apparent elimination half-life estimated after administration of showed a three-fold increase compared with values calculated for free . After the administration of the same dose of , _max obtained showed a 2·5-fold decrease in relation to peak concentrations of free , and the apparent β-half life of encapsulated showed a three-fold increase compared with i.m. . Large-size liposomes containing gentamycin administered i.m. to rabbits gave sustained drug release from the injection site, providing prolonged plasma concentrations of the drug in the body.     

Carnosine, anserine and taurine contents in individual fibres from the middle gluteal muscle of the camel

High muscle camosine and anserine contents contribute significantly to intra-cellular physico-chemical buffering. Our aim was to measure carnosine, anserine and taurine contents directly in individual type I, HA and IIB fibres from the middle gluteus muscle of the camel. Mean carnosine contents in type I, IIA and IIB were 24·6 ±9·2, 39·4 ±11·4 and 42·8 ±18·8 mmol kg⁻¹ dry weight (dw), respectively. Mean anserine contents in type I, HA and IIB fibres were 30·0 ±8·4, 37·3 ±10·1 and 34·5 ±9·7 mmol kg⁻¹ dw, respectively. Mean taurine contents in type I, IIA and HB fibres were 42·4 ±15-9, 203 ±12·9 and 24·7 ±15·9 mmol kg⁻¹ dw, respectively. Higher carnosine contents in type II fibres emphasise the importance of carnosine to intra-muscular acid-base regulation. A specific role for taurine in type I fibres is unclear.     

Pharmacodynamics and enantioselective pharmacokinetics of carprofen in the cat

The pharmacodynamics and enantioselective pharmacokinetics of the arylpropionic acid non-steroidal anti-inflammatory drug, carprofen, were investigated in cats after administration of the racemic mixture (rac-carprofen) at dose rates ranging from 0·7 to 4·0 mg kg⁻¹ intravenously and subcutaneously. A low dose of rac-carprofen (0·7 mg kg⁻¹) partially inhibited the rise in skin temperature at a site of acute inflammation but had no effect on the ex vivo synthesis of serum thromboxane (Tx) B₂. A higher dose (4·0 mg kg⁻¹) inhibited oedematous swelling, although the response was statistically significant at only one time, and also reduced the ex vivo synthesis of serum TxB₂ for 12 hours after intravenous injection or 24 hours after subcutaneous injection. The main features of carprofen pharmacokinetics were a low distribution volume, a relatively long elimination half-life, the predominance of the R(−) enantiomer and a bioavailability (after subcutaneous dosing) of 100 per cent and 92 per cent, respectively, after doses of 0·7 and 4·0 mg kg⁻¹. On the basis of these data, it is suggested that a dose of 4·0 mg kg⁻¹ by both intravenous and subcutaneous routes should be evaluated in clinical subjects.     

Pharmacokinetics of marbofloxacin after a single oral dose to loggerhead sea turtles (Caretta caretta)

The single-dose disposition kinetics of marbofloxacin (MBX) were determined in clinically healthy loggerhead sea turtles (n = 5) after oral (PO) administration of 2 mg kg⁻¹ bodyweight. Marbofloxacin plasma concentrations were determined by DAD–HPLC (LOD/LOQ 0.015/0.05 μg ml⁻¹). Data were subjected to non-compartmental analysis. Following PO administration, marbofloxacin achieved maximum plasma concentrations of 11.66 ± 2.53 mg L⁻¹ at 15.00 ± 3.00 h. The absence of general adverse reactions in the turtles of the study, and the favourable pharmacokinetic properties (long half-life and high maximum plasma concentration) of MBX administered PO at the single-dose of 2 mg kg⁻¹ suggest the possibility of its safe and effective clinical use in loggerhead sea turtles.     

Effects of oral ursodeoxycholic acid in healthy cats on clinicopathological parameters, serum bile acids and light microscopic and ultrastructural features of the liver

A blind, placebo-controlled study evaluated the effects of ursodeoxycholic acid (UDCA) given orally, at a dose of 15 mg kg⁻¹ per day for eight weeks, on the physical condition, haematological and serum biochemical profiles, urinalysis, total serum bile acids ( ) and hepatic histology of four healthy cats. There were no clinically important significant differences between the groups or within the treatment groups in clinicopathological parameters, concentrations or histology. A significant lower concentration/proportion of taurochenodeoxycholic acid was observed in the treated cats (P=0·05). Only one treated cat accumulated measurable quantities of , and the compound appeared to be non-toxic. It did not, increase the concentration of , and accumulated minimally in the serum. It should be investigated for therapeutic use in cats with hepatobiliary disease.     

Effect of stage of gestation and foetal number on plasma concentrations of a pregnancy serum protein (PSP-60) in cattle

This study characterised the peripheral plasma concentration of PSP-60 throughout gestation, and examined the effect of stage of gestation and foetal number on this protein in Holstein cows after non-surgical embryo transfer. Cows (n=12) were divided into two groups; Group 1 contained single embryo recipient cows (n=5), Group 2 contained twin-embryo recipient cows (n=7). Blood was collected approximately every third day from day 0 (first day of standing oestrus), then daily for the last 10 days of gestation and until one day post-partum. Two of the twin-embryo recipient cows had abnormal pregnancies, consequently data from them was considered separately. In both groups PSP-60 increased progressively from about day 20 post-oestrus to 20 days pre-partum (from 0·9 ± 0·2 to 49·7 ± 8·7 ng ml⁻¹, and from 1·3 ± 0·6 to 115 ± 34·9 ng ml⁻¹ (mean ± SEM), in singleton and twin-bearing groups, respectively). The mean concentrations between 20 and 10 days pre-partum increased dramatically by about six-fold (P<0·001) in singleton-bearing cows (from 49·7 ± 8·7 ng ml⁻¹ to 2838 ± 73·7 ng ml⁻¹) to over two-fold in twin-bearing cows (from 115 ± 34·9 ng ml⁻¹ to 284 ± 98·2 ng ml^-1). The mean concentrations of the two groups were indistinguishable between 10 days pre-parturn and parturition. Cows giving birth prematurely to stillborn calves or to a schistosomus reflexus calf exhibited abnormal PSP-60 profiles. Our findings indicate that peripheral plasma PSP-60 concentrations are correlated to the stage of gestation and foetal number, and assist in predicting foeto-placental viability.     

Rumen degradation characteristics of sweet potato foliage and performance by local and crossbred calves fed milk and foliage from three cultivars

The study investigated rumen dry matter (DM) degradability characteristics in a completely randomized design and the effects of milk, sweet potato foliage (SPF) from three cultivars (A = TIS-87/0087; B = TIS-8164; C = TIS-2532.OP.1.13), dried brewers' grains (DBG) and cottonseed meal (CSM) as supplements to Panicum maximum (Panicum) for pre-weaned calves in randomized complete block designs. Diet 1 = milk + SPF-A foliage + Panicum, Diet 2 = milk + SPF-B foliage + Panicum, Diet 3 = milk + SPF-C foliage + Panicum, and Diet 4 = milk + DBG & CSM + Panicum (as control). Dry matter (130 ± 0.4 to 864 ± 3.9 g kg^− 1), ash (54 ± 4.2 to 173 ± 2.8 g kg^− 1 DM), OM (827 ± 4.2 to 946 ± 5.7 g kg^− 1 DM), N (7.4 ± 0.6 to 38.6 ± 1.4 g kg^− 1 DM), and NDF (439 ± 1.4 to 774 ± 8.5 g kg^− 1 DM) contents were highly significant (P < 0.01). In Trial I, 16 pre-weaned calves were used over 70 d with milk intake (34.8 ± 4.4 ml kg W^− 0.75 d^− 1), Panicum DMI (22.3 ± 2.77 g kg W^− 0.75 d^− 1), total DMI (35.7 ± 2.83 g kg W^− 0.75 d^− 1), and LWG (198 ± 44.6 g d^− 1) not significantly different (P > 0.05). Supplement DMI varied (P < 0.05) from 11.6 g kg W^− 0.75 d^− 1 in Diet 3 to 16.6 g kg W^− 0.75 d^− 1 in Diet 4. In Trial II, 16 pre-weaned local and crossbred calves were involved over 77 d with initial age of calves, Panicum intake, metabolic DMI, and LWG similar (P > 0.05) among crosses. Birthweight varied (P < 0.05) from 17.3 kg for N'Dama × Jersey crosses to 21.2 kg for White Fulani × Brown Swiss crosses. Supplement and total DMI ranged (P < 0.05) from 172 to 483 g d^− 1 for N'Dama × Jersey crosses to 233 and 674 g d^− 1 for non-inseminate or purebred calves, respectively. The LWG in the White Fulani × Brown Swiss and the N'Dama × Jersey calves were respectively 30% and 24% better, though not significantly, than purebred calves. In Trial III, rumen DM degradability characteristics of feeds in three N'Dama steers showed no significant differences (P > 0.05) in slowly degradable fraction (b) and rate of degradation of b (c). Soluble fraction (a), 48-h degradation, potential degradability (PD) and effective degradability (ED) varied significantly (P < 0.05) and were lowest in Panicum, but similar for foliage among the three sweet potato cultivars. Panicum fodder showed improvements in degradation characteristics with supplementation.     

Plasma glucose and cortisol responses to exogenous insulin in fasted donkeys

Susceptibility to equine hyperlipaemia is increased by poor food intake. To assess the contribution of changes in insulin sensitivity, plasma glucose and cortisol responses to an intravenous insulin challenge (0·4 kg⁻¹ bodyweight) were compared with those observed after saline administration in six donkeys fasted either overnight or for three days. Three days of fasting decreased both the rate of insulin-induced hypoglycemia and the maximal hypoglycemic response. A transitory increase in plasma cortisol which peaked within one to four hours of insulin administration was observed in three of the six overnight-fasted donkeys and in all of the three-day fasted donkeys; inter-animal variation appeared to exist in the responsiveness of the hypothalamic-pituitary-adrenocortical ( ) axis to stimulation by insulin-induced hypoglycemia. Fasting is likely to present a risk of equine hyperlipaemia, at least in part, by the reduction in tissue sensitivity to the glucoregulatory action of insulin.     

Pharmacokinetic, metabolism and withdrawal time of orphenadrine in camels (Camelus dromedarius) after intravenous administration

The pharmacokinetics of orphenadrine (ORPH) following a single intravenous (i.v.) dose was investigated in six camels (Camelus dormedarius). Orphenadrine was extracted from the plasma using a simple sensitive liquid–liquid extraction method and determined by gas chromatography/mass spectrometry (GC/MS). Following i.v. administration plasma concentrations of ORPH decline bi-exponentially with distribution half-life (t_1/2α) of 0.50 ± 0.07 h, elimination half-life (t_1/2β) of 3.57 ± 0.55 h, area under the time concentration curve (AUC) of 1.03 ± 0.10 g/h l⁻¹. The volume of distribution at steady state (Vd_ss) 1.92 ± 0.22 l kg⁻¹, volume of the central compartment of the two compartment pharmacokinetic model (V_c) 0.87 ± 0.09 l kg⁻¹, and total body clearance (Cl_T) of 0.60 ± 0.09 l/h kg⁻¹. Three orphenadrine metabolites were identified in urine samples of camels. The first metabolite N-desmethyl-orphenadrine resulted from N-dealkylation of ORPH with molecular ion m/z 255. The second N,N-didesmethyl-orphenadrine, resulted from N-didesmethylation with molecular ion m/z 241. The third metabolite, hydroxyl-orphenadrine, resulted from the hydroxylation of ORPH with molecular ion m/z 285. ORPH and its metabolites in camel were extensively eliminated in conjugated form. ORPH remains detectable in camel urine for three days after i.v. administration of a single dose of 350 mg orphenadrine aspartate.