Pharmacokinetics of pradofloxacin and doxycycline in serum, saliva, and tear fluid of cats after oral administration

The pharmacokinetic properties of pradofloxacin and doxycycline were investigated in serum, saliva, and tear fluid of cats. In a crossover study design, six cats were treated orally with a single dose of pradofloxacin (Veraflox^® Oral Suspension 2.5%) and doxycycline (Ronaxan^® 100 mg) at 5 mg/kg body weight. Following administration, samples of serum, saliva, and tear fluid were taken in regular intervals over a period of 24 h and analysed by turbulent flow chromatography/tandem mass spectrometry. All values are given as mean ± SD. Pradofloxacin reached a mean maximum serum concentration ( C _max) of 1.1 ± 0.5 μg/mL after 1.8 ± 1.3 h ( t _max). In saliva and tear fluid, mean C _max was 6.3 ± 7.0 and 13.4 ± 20.9 μg/mL, respectively, and mean t _max was 0.5 ± 0 and 0.8 ± 0.3 h, respectively. Doxycycline reached a mean C _max in serum of 4.0 ± 0.8 μg/mL after 4.3 ± 3.2 h. Whilst only at two time-points doxycycline concentrations close to the limit of quantification were determined in tear fluid, no detectable levels were found in saliva. The high concentrations of pradofloxacin in saliva and tear fluid are promising to apply pradofloxacin for the treatment of conjunctivitis and upper respiratory tract infections in cats. As doxycycline is barely secreted into these fluids after oral application the mechanisms of its clinical efficacy remain unclear.     

Investigation of pharmacokinetic parameters of tiamulin after intramuscular and subcutaneous administration in normal dogs

Laber, G. Investigation of pharmacokinetic parameters of tiamulin after intramuscular and subcutaneous administration in normal dogs. J. vet. Pharmacol. Therap. 11 , 45–49.
Kinetic variables for tiamulin in the normal dog have been determined. Serum concentrations of tiamulin were compared after intramuscular (i.m.) and subcutaneous (s.c.) administration of a single dose of tiamulin. Following a single i.m. dose of 10 mg/kg body weight, the compound was calculated to have a C_max= 0.61 ± 0.15 μg/ml, a T _max= 6 h and a t _½= 4.7 ± 1.4 h. Tiamulin showed dose-dependent pharmacokinetics when given as a single s.c. dose of either 10 mg or 25 mg/kg body weight. For the lower dose, the values C_max= 1.55 ± 0.11 μg/ml, T _max= 8 h and 1 _max= 4.28 ± 0.18 h were obtained. For the higher dose C _max= 3.14 ± 0.04 μg/ml, T _max= 8 h and t _½= 12.4 ± 3.4 h were calculated. When tiamulin was administered subcutaneously at a dose rate of 10 mg/kg body weight, higher and better maintained serum levels were achieved than those following i.m. administration. After repeated s.c. doses no significant accumulation of tiamulin occurred. Assuming that a continuous effective serum concentration is necessary throughout the course of therapy, these data would indicate that tiamulin should be given every 24 h.     

Effects of Exogenous Tumour Necrosis Factor-α on the Secretory Function of the Bovine Reproductive Tract Depend on Tumour Necrosis Factor-α Concentrations

The aim of study was to correlate tumour necrosis factor-α (TNF) infused doses used with the TNF concentrations achieved and with the secretory function of both the ovary and the uterus in cows. We evaluated the concentrations of progesterone (P4), prostaglandin (PG)F_2α, PGE₂ nitric oxide (NO) and TNF in the jugular vein and vena cava caudalis as parameters of exogenous TNF action on the female reproductive tract. Aortae abdominalis of cows (n = 18) were infused with saline or two doses of TNF (luteolytic – 1 μg or luteotrophic – 10 μg). In the peripheral blood, 1 μg TNF concentrations achieved within the range of 30–45 pg/ml, and 10 μg TNF provoked a sharp increase in achieved concentrations at a range of 250–450 pg/mL). The TNF concentrations achieved in vena cava caudalis were five to six times higher than that in peripheral blood (p < 0.001). One microgram TNF increased PGF_2α and NO (p < 0.001) and decreased P4 (p < 0.05). The higher TNF dose stimulated P4 and PGE₂ (p < 0.01). TNF infusion at luteolytic dose achieved its concentrations at the physiological range previously observed in cows. Luteotrophic TNF dose achieved the concentrations in vena cava caudalis that are much higher than physiological level and were previously noted in pathological circumstances (i.e. mastitis , metritis ).     

Retinol-Binding Protein in Serum and Urine of Hyperthyroid Cats before and after Treatment with Radioiodine

Background: Retinol-binding protein (RBP) is suggested as a clinically useful marker of renal function in cats.
Hypothesis: Serum and urinary RBP concentrations in hyperthyroid (HT) cats differ from those in healthy (H) cats; radioiodine (¹³¹I) treatment influences serum and urinary RBP concentrations in HT cats.
Animals: Ten HT and 8 H cats.
Methods: RBP concentration was evaluated in feline serum and urine samples from a prospective study.
Results: There was a significant ( P = .003) difference in the urinary RBP/creatinine (uRBP/c) ratios of H (−) and untreated HT (1.4 ± 1.5 × 10⁻² μg/mg) cats. Serum total thyroxine concentration (1.8 ± 1.9 μg/dL, 24 weeks) and uRBP/c (0.6 ± 1.0 × 10⁻² μg/mg, 24 weeks) decreased significantly ( P < .001) in HT cats at all time points after treatment with ¹³¹I, and these variables were significantly correlated with one another ( r = 0.42, P = .007). Serum RBP concentrations from HT cats (199 ± 86 μg/L) did not differ significantly ( P = .98) from those of H cats (174 ± 60) and did not change after treatment with ¹³¹I (182 ± 124 μg/L, P = .80).
Conclusion and Clinical Importance: The presence of urinary RBP in HT cats is a potential marker of tubular dysfunction that is correlated to thyroid status, although it is independent of circulating RBP concentrations. The decreased uRBP/c combined with the absence of changes in serum RBP after treatment suggests that the suspected tubular dysfunction was partly reversible with treatment of ¹³¹I.     

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.     

Disposition of human drug preparations in the horse. III. Orally administered alclofenac

Concentrations of the non-steroidal anti-inflammatory drug (NSAID) alclofenac were determined by a sensitive high performance liquid chromatographic procedure in plasma and urine of horses following oral administration of a dose of 3 g. In plasma, alclofenac was present in detectable concentrations for 72 h. The plasma disposition in individual horses was best described by a bi-compartmental model with two successive rate constants ka₁= 0.05 ± 0.06 h^-1 and ka₂= 0.06 ± 0.01 h^-l. Alclofenac half-lives t _½ and t _1/2β were 1.0 ± 0.8 h and 6.9 ± 1.5 h, respectively. Maximal concentrations (38.9 ± 16.2 μg/ml) were obtained after 8.5 ± 2.4 h. Alclofenac was detected in urine for at least 48 h after dosing. The percentage of the dose excreted as unchanged alclofenac in 12 h was very low (0.68 ± 0.19%), total (free + conjugated) alclofenac accounted for 2.16 ± 0.55% of the dose.     

Pharmacokinetics of chloramphenicol in the neonatal horse

Chloramphenicol sodium succinate was administered as an intravenous bolus (50 mg/kg) to eight foals which weighed 49–57 kg (mean ± 1 standard deviation = 53.19 ± 2.66) each, and were 1–9 days (4.5 ± 2.56) of age. The drug was rapidly distributed and followed first-order elimination. Mean pharmacokinetic values were: zero-time serum concentration (C₀) = 36.14 μg/ml (±14.80); apparent specific volume of distribution ( V_d ) = 1.614 1/kg (±0.669); and elimination rate constant ( K ) = 0.7295 h^-1 (±0.3066) which corresponds to a biological half-life ( t _1/2) = 0.95 h. These values do not differ greatly from those reported for adult horses and ponies.
A suspension of chloramphenicol was administered by nasogastric tube (50 mg/kg) to a second group of seven foals which weighed 49 to 57 kg (51.34 ± 2.82) each and were 1 to 7 days (4.43 ± 1.90) of age. A mean peak serum chloramphenicol concentration of 23.97 μg/ml (±7.06) was achieved 1.14h (±0.63) after administration. The bioavailability of this preparation was 83.27 percent.     

Pharmacokinetics of a single bolus intravenous, intramuscular and subcutaneous dose of disodium fosfomycin in horses

Pharmacokinetic parameters of fosfomycin were determined in horses after the administration of disodium fosfomycin at 10 mg/kg and 20 mg/kg intravenously (IV), intramuscularly (IM) and subcutaneously (SC) each. Serum concentration at time zero (C_S0) was 112.21 ± 1.27 μg/mL and 201.43 ± 1.56 μg/mL for each dose level. Bioavailability after the SC administration was 84 and 86% for the 10 mg/kg and the 20 mg/kg dose respectively. Considering the documented minimum inhibitory concentration (MIC₉₀) range of sensitive bacteria to fosfomycin, the maximum serum concentration (Cmax) obtained (56.14 ± 2.26 μg/mL with 10 mg/kg SC and 72.14 ± 3.04 μg/mL with 20 mg/kg SC) and that fosfomycin is considered a time-dependant antimicrobial, it can be concluded that clinically effective plasma concentrations might be obtained for up to 10 h administering 20 mg/kg SC. An additional predictor of efficacy for this latter dose and route, and considering a 12 h dosing interval, could be area under the curve AUC_0-12/MIC₉₀ ratio which in this case was calculated as 996 for the 10 mg/kg dose and 1260 for the 20 mg/kg dose if dealing with sensitive bacteria. If a more resistant strain is considered, the AUC_0-12/MIC₉₀ ratio was calculated as 15 for the 10 mg/kg dose and 19 for the 20 mg/kg dose.     

Plasma and urine disposition and dose proportionality of ceftiofur and metabolites in dogs after subcutaneous administration of ceftiofur sodium

Nine male dogs (10.3–13.5 kg body weight) were randomly assigned to three groups of three dogs each and administered ceftiofur sodium subcutaneously as a single dose of 0.22, 2.2, or 4.4 mg ceftiofur free acid equivalents/kg body weight. Plasma and urine samples were collected serially for 72 h and assayed for ceftiofur and metabolites (derivatized to desfuroylceftiofur acetamide) using high-performance liquid chromatography. Urine concentrations remained above the MIC ₉₀ for Escherichia coll (4.0 μg/mL) and Proteus mirabilis (1.0 μg/mL) for over 24 h after doses of 2.2 mg/kg (8.1 μg/mL) and 4.4 mg/kg (29.6 μg/mL), the interval between treatments for ceftiofur sodium in dogs, whereas urine concentrations 24 h after dosing at 0.22 mg/kg (0.1 mg/Ib) were below the MIC ₉₀ for E.coli and P. mirabills (0.6 μg/mL). Plasma concentrations were dose-proportional, with peak concentrations of 1.66 ± 0.0990 μg/mL, 8.91 ± 6.42 μg/mL, and 26.7 ± 1.07 μg/mL after doses of 0.22, 2.2, and 4.4 mg/kg, respectively. The area under the plasma concentration versus time curve, when normalized to dose, was similar across all dosage groups.     

Pharmacokinetics and tissue residues of norfloxacin and its N-desethyl- and oxo-metabolites in healthy pigs

The pharmacokinetic properties of norfloxacin were determined in healthy pigs after single intramuscular (i.m.) and intravenous (i.v.) dosage of 8 mg/kg body weight After i.m. and i.v. administration, the plasma concentration-time graph was characteristic of a two-compartment open model. After single i.m. administration, norfloxacin was absorbed rapidly, with a t _max of 1.46 ± 0.06 h. The elimination half-life ( t _1/2β) and the mean residence time of norfloxacin in plasma were 4.99 ± 0.28 and 6.05 ± 0.22 h, respectively, after i.m. administration and 3.65 ± 0.16 and 3.34 ± 0.16 h, respectively, after i.v. administration. Intramuscular bioavailability was found to be 53.7 ± 4.4%. Plasma concentrations greater than 0.2 μg/mL were achieved at 20 min and persisted up to 8 h post-administration. Maximal plasma concentration was 1.11 ± 0.03 μg/mL. Statistically significant differences between the two routes of administration were found for the half-lives of both distribution and elimination phases ( t _1/2α, t _1/2β) and apparent volume of distribution (V_d(area)). In pigs, norfloxacin was mainly converted to desethylenenorfloxacln and oxonorfloxacin. Considerable tissue concentrations of norfloxacin, desethylenenorfloxacin, and oxonorfloxacin were found when norfloxacin was administered intramuscularly (8 mg/kg on 4 consecutive days). The concentration of the parent fluoroquinolone in liver and kidney ranged between 0.015 and 0.017 μg/g on day 12 after the end of dosing.     

Alpha-adrenoceptors in equine digital veins: Evidence for the presence of both alpha1 and alpha2-receptors mediating vasoconstriction

Rings of equine digital vein examined under conditions of isometric tension recording constricted to alpha-adrenoceptor agonists with an order of potency of 5-bromo-6-[2-imidazolin-2-yl-amino]-quinoxaline bitartrate (UK 14304) = noradrenaline > 6-Allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo-(4,5-d) azepine (BHT-920) > phenylephrine > dopamine > methoxamine. The maximum force generated was greatest for the non-selective agonist noradrenaline and lowest for the alpha₂-selective agonist BHT-920 with the other agonists between these two extremes. Selective inactivation of alpha₁-adrenoceptors (achieved by treating yohimbine-protected tissues with phenoxybenzamine) reduced the maximum responses of all agonists, the EC₅₀ values of UK 14304, BHT-920 and noradrenaline and increased the EC₅₀ values of phenylephrine and methoxamine. Prazosin (30 n M ) had no inhibitory effect on responses to low concentrations of BHT-920 and UK 14304 and caused competitive inhibition of responses to phenylephrine and noradrenaline giving pK_b values of 8.49 ± 0.18 and 8.23 ± 0.14, respectively. Yohimbine (0.1 μ M ) caused significant competitive inhibition of responses to BHT-920 and noradrenaline with calculated pK_b values of 8.43 ± 0.11 for BHT-920 and 7.43 ± 0.31 for noradrenaline and non-competitive inhibition of responses to UK 14304. 2-[2-methoxy-1,4-benzodioxan-2-yl]-2-imidazoline (RX 821002; 10 n M ) caused competitive inhibition of responses to BHT-920 (pK_b 9.04 ± 0.27) and dopamine (pK_b 8.2 ± 0.2). These data indicate that equine digital veins possess both post-synaptic alpha₁ and alpha₂-adrenoceptors.     

Pharmacokinetics and bioequivalence of parenterally administered doramectin in cattle

Plasma concentrations of doramectin in 40 cattle dosed by subcutaneous (sc) or intramuscular (i.m.) injection (200 μg/kg) were compared to assess the bioequivalence of the two routes of administration. Peak concentration ( C _max), and areas under the concentration curve ( AUC_0– ) were determined from plasma concentrations. Animals treated by the sc route showed a mean AUC_0– of 457 ± 66 ng±day/mL (± SD) and a mean C _max of 27.8 ± 7.9 ng/mL. Results from the i.m. treatment group showed a mean AUC _0– of 475 ± 82 ng-day/mL and a mean C _max of 33.1 ± 9.0 ng/mL Absorption constants ( k _a) determined by modelling were 0.542 ± 0.336 day^-1after sc administration and 0.710 ± 0.357 day^-1after i.m. administration. The 90% confidence limits on the difference between mean AUC _0– values for the sc and i.m. groups fell within 20% of the mean value for the subcutaneous group. C _max was somewhat greater for the i.m. route. The 90% confidence limits on the difference in mean In ( T _max+1) also fell within 20% of the mean sc value. Based on this analysis, bioequivalence of the sc and i.m. formulation has been established.     

The effects of pentoxifylline infusion on plasma 6-keto-prostaglandin F1α and ex vivo endotoxin-induced tumour necrosis factor activity in horses

Pentoxifylline (7.5 mg/kg) was bolused intravenously to eight healthy horses and was immediately followed by infusion (1.5 mg/kg/h) for 3 h. Clinical parameters were recorded and blood samples were collected for 24 h. Plasma was separated and concentrations of pentoxifylline, its reduced metabolite I, and 6-keto-prostaglandin F_1α were determined. Heparinized whole blood was also incubated ex vivo with 1 ng Escherichi coli endotoxin/mL blood for 6 h before determination of plasma tumour necrosis factor activity. The peak plasma concentrations of pentoxifylline and metabolite I occurred at 15 min after bolus injection and were 9.2± 1.4 and 7.8± 4.3 μg/mL, respectively. The half-life of elimination ( t _½β) of pentoxifylline was 1.44 h and volume of distribution ( V d_area) was 0.94 L/kg. The mean plasma concentration of 6-keto-prostaglandin F_1α increased over time, with a significant increase occurring 30 min after the bolus administration. Ex vivo plasma endotoxin-induced tumour necrosis factor activity was significantly decreased at 1.5 and 3 h of infusion. These results indicate that infusion of pentoxifylline will increase 6-keto-prostaglandin F_1α and significantly suppress endotoxin-induced tumour necrosis factor activity in horses during the period of infusion.     

Kinetics and residues after intraperitoneal procaine penicillin G administration in lactating dairy cows

This paper describes the pharmacokinetic profile of procaine penicillin G after intraperitoneal (IP) administration in eight lactating dairy cows. Procaine pencillin G (PPG, 21 000 IU/kg) was deposited into the abdominal cavity of each cow following an incision in the right paralumbar fossa. Blood and milk samples were taken over the following 10 days, at which point the cows were euthanized. Plasma, milk, muscle, liver, and kidney penicillin concentrations were determined by HPLC, with a limit of quantification of 5 ng/mL for plasma and milk and 40 ng/g for tissue samples. A noncompartmental method was used to analyze plasma kinetics. The mean pharmacokinetic parameters (±SD) were: C _max, 5.5 ± 2.6 μg/mL; T _max, 0.75 ± 0.27 h; AUC _0-∞, 10.8 ± 4.9 μg·h/mL; MRT , 2.2 ± 0.9 h. All milk from treated cows contained detectable penicillin residues for a minimum of three milkings (31 h) and maximum of five milkings (52 h) after administration. Concentrations of penicillin in all muscle, liver, and kidney samples taken 10 days postadministration were below the limit of quantification. Necropsy examinations revealed foci of hemorrhage on the rumenal omentum of most cows but peritonitis was not observed. Systemic inflammation as determined by change in leukogram or plasma fibrinogen was noted in one cow. The results of this study demonstrate that IP PPG is absorbed and eliminated rapidly in lactating dairy cows.     

Concentrations of thyroid hormones and iodothyronine binding proteins in serum of the koala (Phascolarctos cinereus)

Objective To examine circulating total and free thyroid hormone (T₃ and T₄) concentrations, determine serum iodothyronine binding characteristics and estimate thyroid stimulating hormone (TSH) activity in sera of coastal and inland koalas.
Design A prospective study.
Procedure Koala serum T₃ and T₄ were measured by radioimmunoassay. T₄ binding parameters were determined by radioligand binding and electrophoresis. Koala TSH values were determined by bioassay.
Results Mean total T₄ concentrations were 3.2 ± 2.1 nM although values were significantly higher in inland-dwelling females in comparison to coastal-dwelling males. Free T₄ was 3.3 ± 2.1 pM. Total and free T₃ were 0.4 ± 0.2 nM and 1.4 ± 0.9 pM respectively, although these values were at the lower end of the assay detection limit and should be viewed with reservation. Electrophoresis of [¹²⁵I]-T₄-labelled serum revealed only two proteins of electrophoretic mobility similar to human transthyretin (TTR) and albumin. Scatchard analysis of T₄ binding to serum gave a curvilinear plot, which could be resolved into two binding sites with affinities identical to that of TTR and albumin but both of low concentration. The bioactivity of the TSH present in the sera was measured using a cell line (JP09) transfected with the human TSH receptor. The mean level of stimulation found in the sera corresponded to a bovine TSH activity of less than 10 mU/L.
Conclusion These results suggest that the serum concentrations of free and total thyroid hormones in koalas are low compared to other marsupials and very low compared to eutherian mammals. The mechanism of maintenance of euthyroidism in this species remains to be determined.     

Cephalothin and Cefazolin In Vitro Antibacterial Activity and Pharmacokinetics in Dogs

The periods of time that cephalothin and cefazolin serum concentration remained above minimum inhibitory concentration (MIC) for beta hemolytic, coagulase positive staphylococcal, and Escherichia coli clinical isolates were compared. Cephalothin and cefazolin were similarly very effective in vitro against staphylococcal isolates, with an MIC₉₀ of 0.12 μg/mL and 0.25 μg/mL, respectively. In contrast, cefazolin was more effective than cephalothin against E coli isolates; the cefazolin MIC₉₀ for E coli was 16 μg/mL and for cephalothin 64 μg/mL. Cefazolin (20 mg/kg intravenously [IV]) serum concentration remained more than MIC₉₀ for E coli isolates significantly longer than serum concentration of cephalothin (40 mg/kg IV) ( P <.001).     

Comparison of Two Doses of the GnRH Antagonist, Acyline, for Pregnancy Termination in Bitches

Gonadotropin-releasing hormone (GnRH) antagonists are particularly useful when a rapid inhibitory effect on the gonadal axis is required. The aim of this study was to test the efficacy and clinical safety of a low and high dose of the third generation GnRH antagonist, acyline, on pregnancy termination in female dogs. The effect of the antagonist on the progesterone (P₄) serum concentration was also described. Twenty-one mid-pregnant bitches were randomly assigned to a single subcutaneous (SC) dose of a placebo (PLACE; n = 7), a low (ACY-L; 110 μg/kg; n = 6) or high (ACY-H; 330 μg/kg; n = 8) dose of acyline. The animals were followed up for 15 days. All ACY treated but no placebo-treated animals terminated their pregnancy by abortion (p < 0.01). The ACY-L and ACY-H groups interrupted their pregnancy 7 ± 1.9 and 6.4 ± 1.3   days after treatment, respectively (p = 0.7). A significant interaction between treatment and day was found (p < 0.01) for P₄ serum concentrations when PLACE was compared with both ACY groups. No difference was found for this hormone between both ACY groups (p > 0.05) where P₄ diminished throughout the study. The decreasing rate varied among animals and was closely related to the time of abortion when P₄ reached basal concentrations. In PLACE animals, gestation progressed normally and P₄ did not change throughout the study (p > 0.05). None of the bitches presented side effects. It was concluded that acyline safely terminated mid-pregnancy by permanently decreasing P₄ serum concentrations.     

Pharmacokinetics and bioavailability of doxycycline in turkeys

The pharmacokinetic parameters of doxycycline (DOX) were determined in 3 day, 3-, 6- and 12-week-old fasted turkeys, after a single intravenous (i.v.) dose of 25 mg doxycycline. HCl/kg body weight. Doxycycline disposition fitted an open two-compartment model. The mean (± SD) elimination half-life was 10.6 ± 0.7, 10.8 ± 1.5, 7.9 ± 1.4 and 10.0 ± 0.9 h in 3 day, 3-, 6- and 12-week-old turkeys, respectively. Mean (± SD) total body clearance was 0.19 (± 0.01), 0.27 (± 0.03), 0.11 (± 0.03) and 0.06 (± 0.01) L/h.kg in 3 day, 3-, 6- and 12-week-old turkeys, respectively. The steady-state volume of distribution was 1.77 (± 0.2), 2.1 (± 0.2), 0.7 (± 0.4) and 0.5 (± 0.2) L/kg in turkeys of the above mentioned ages, respectively. The AUC value significantly increased with the age of the turkeys. An oral doxycycline solution at a single dose of 25 mg/kg of body weight was administered to 3 day, 3-, 6- and 12-week-old turkeys. The maximal plasma concentrations in fasted turkeys were 3.8, 5.6, 7.4 and 5.7 μg/mL, with t _max values of 4.7, 1.5, 2.8 and 5.4 h, for the different ages, respectively. In fed turkeys the C _max values were 2.5, 6.1, 4.8 and 3.0 μg/mL, with t _max values of 4.2, 5.3, 4.5 and 7.5 h, respectively. The absolute bioavailability in fasted turkeys varied between 25.0 ± 9.0% (for 12-week-old birds) and 63.5 ± 7.1% (for 3-week-old birds). The relative bioavailability varied between 40.0 ± 13.0% (for 12-week-old birds) and 83.7 ± 14.3% (for 3-week-old birds).     

Effects of age and indomethacin on response and sensitivity of pulmonary artery to phenylephrine and to histamine in pigs

The vasoconstrictor effects of phenylephrine and histamine were investigated in isolated strips of pulmonary arteries in pigs during ageing. Interactions between phenylephrine-induced responses and arachidonic acid derivatives were also studied by incubating the blood-vessels with indomethacin. Potency (pD2 values) and maximal effects (E_maxx) recorded in 5-week-old piglets (group I, n = 5) with phenylephrine [5.71 ± 0.17 and 0.76 ± 0.22 g/mg of dry tissue respectively (mean ± SEM)] were similar to values found in 12-week-old animals (group 2, n = 5) (5.49 ± 0.30 and 1.06 ± 0.27 g/mg of dry tissue respectively). The sensitivity and responsiveness of tissues to this agonist were significantly reduced in 26-week-old mature pigs (group 3, n = 6) as indicated by the decrease in pD2 (3.91 ± 0.23; P < 0.01) and E_max (0.27 ± 0.13 g/mg of dry tissue; P < 0.05) values observed in this group. Histamine (10^_3M)-induced maximal responses (E_max) were significantly higher in group 2 (2.23 ± 0.49 g/mg) than in group 1 (0.85 ± 0.11 g/mg; P < 0.05) and in group 3 (0.48 ± 0.10 g/mg; P < 0.01). In 5-week-old animals, indomethacin (3.10˜⁵M) significantly ( P < 0.05) shifted the concentration-response curve to phenylephrine to the right (0.28 log. units) and depressed contractions to this drug as shown by the significant decrease of 39.5% ( P < 0.05) in E_max. This cyclo-oxygenase inhibitor had no effect in other groups. These data indicate that phenylephrine is a potent and effective vasoconstrictor agent for the main pulmonary arteries in 5-week-old piglets and that alpha-1-adrenergic-induced contractions are enhanced by cyclo-oxygenase products. These findings can be related with the high reactivity of pulmonary vascular smooth muscles in these animals.     

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.