Changes in serum C-reactive protein levels in dogs with various disorders and surgical traumas

The serum levels of C-reactive protein (CRP) produced as an inflammatory response in dogs with various disorders and surgical traumas were measured by enzyme-linked immunoabsorbent assay and slide reversed passive latex agglutination test (RPLA). The CRP levels were greatly increased 1–2 days after surgery in most of the dogs (n=29) subjected to surgery. These levels had markedly decreased by the time the sutures were removed. In dogs with various disorders (n=58), the serum CRP levels at first diagnosis were high in infectious diseases. In dogs from which paired serum samples were examined, the serum CRP usually showed a decrease with improvement in the condition (n=11) or a terminal increase (n=4) but, conversely, some showed an increase with improvement in the condition (n=3).Abbreviations CRP C-reactive protein - ELISA enzyme-linked immunoabsorbent assay - Latex soap free latex - RPLA reversed passive latex agglutination     

Evaluation of intravenous administration of meloxicam for perioperative pain management following stifle joint surgery in dogs

OBJECTIVE: To compare preoperative administration of meloxicam and butorphanol to perioperative administration of butorphanol alone for control of postoperative signs of pain in dogs. ANIMALS: 40 client-owned dogs scheduled for surgical repair of a cranial cruciate ligament rupture. PROCEDURE: Group-1 dogs received butorphanol (0.2 mg/kg, IV) and meloxicam (0.2 mg/kg, IV) just prior to surgery. Group-2 dogs received butorphanol just prior to surgery (0.2 mg/kg, IV) and at incision closure (0.1 mg/kg, IV). Pain assessment began 1 to 2 hours before surgery and from extubation until 24 hours after surgery by obtaining the following measurements: the visual analog scale (VAS) score, cumulative pain score (CPS), adjusted cumulative pain score, modified cumulative pain score, and the adjusted modified cumulative pain score (AMCPS). Serum cortisol concentration was measured between 12 to 24 and between 1 to 2 hours prior to surgery, and at 30 minutes, and 1, 2, 4, 8, 18, and 24 hours after extubation. RESULTS: No significant differences between treatment groups were observed in CPS or VAS score. At 8, 9, 10, and 11 hours after extubation, meloxicam-butorphanol-treated dogs had a significantly lower AMCPS, compared with butorphanol-alone-treated dogs. Total serum cortisol concentration (area under the curve) during the measurement period was significantly lower in meloxicam-butorphanol-treated dogs, compared with butorphanol-alone treated dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Preoperative single dose administration of meloxicam-butorphanol is equivalent to or slightly better than the administration of 2 perioperative doses of butorphanol for the control of postoperative signs of pain in dogs.     

Serum C-reactive protein concentration as an indicator of remission status in dogs with multicentric lymphoma

BACKGROUND: The acute-phase protein C-reactive protein (CRP) is used as a diagnostic and prognostic marker in humans with various neoplasias, including non-Hodgkin's lymphoma. OBJECTIVE: To evaluate if CRP could be used to detect different remission states in dogs with lymphoma. ANIMALS: Twenty-two dogs with untreated multicentric lymphoma. METHODS: Prospective observational study. Blood samples were collected at the time of diagnosis, before each chemotherapy session, and at follow-up visits, resulting in 287 serum samples. RESULTS: Before therapy, a statistically significant majority of the dogs (P = .0019) had CRP concentrations above the reference range (68%, 15/22). After achieving complete remission 90% (18/20) of the dogs had CRP concentrations within the reference range, and the difference in values before and after treatment was statistically significant (P < .001). CRP concentrations of dogs in complete remission (median, 1.91; range, 0.2-103) were significantly different (P = .031) from those of dogs with partial remission (median, 2.48; range, 0-89), stable disease (median, 1.77; range, 1.03-42.65), or progressive disease (median, 8.7; range, 0-82.5). There was profound variation of CRP measurements within each dog. CONCLUSIONS: CRP is useful in determining complete remission status after treatment with cytotoxic drugs. However, the individual variation between dogs means CRP concentration is not sufficiently different in other remission states to permit its use in monitoring progression of the disease. Greater reliability in determining remission status might be achieved by combining CRP concentration with other serum markers.     

Serum C-reactive protein and immune responses in dogs inoculated withBordetella bronchiseptica (phase I cells)

Eight Beagle dogs were inoculated intrabronchially with 5×10⁹ live, avirulent cells ofBordetella bronchiseptica L-414 strain (phase I cells) (B. bronchiseptica) to investigate the serum levels of their C-reactive protein, the white blood cell counts, the antibody responses toB. bronchiseptica in the sera and tracheal secretions, and the effects of prednisolone given to four of the dogs on C-reactive protein (CRP), white blood cells (WBC) and immune responses. In two Beagle dogs inoculated intrabronchially with sterile physiological saline, the concentrations of CRP and the WBC counts did not increase. CRP was markedly increased one day after inoculation in the dogs inoculated withB. bronchiseptica to 385.0–720.0 µg/ml (mean 498±132 µg/ml) in the group given theB. bronchiseptica inoculation only, and to 372.0–649.0 µg/ml (mean 551±106 µg/ml) in the group treated with prednisolone following inoculation ofB. bronchiseptica, as determined by an enzyme-linked immunosorbent assay (ELISA). The CRP levels were 23–95 times the pre-inoculation values, which indicated that prednisolone had no effect on the production of CRP. In the prednisolone-treated group, the WBC count increased and stayed at an increased level for approximately 12 days. An indirect fluorescent antibody test led to the detection of anti-B. bronchiseptica IgM and IgG antibodies in the sera from 5 days afterB. bronchiseptica inoculation and S-IgA and IgG anti-B. bronchiseptica antibodies in the tracheal secretions on the day after the challenge exposure toB. bronchiseptica. The increase in CRP after challenge exposure toB. bronchiseptica was significantly (p<0.05) smaller than that found after the first inoculation ofB. bronchiseptica.Abbreviations CRP C-reactive protein - ELISA enzyme-linked immunosorbent assay - FHA filamentous haemagglutinin - IFA indirect fluorescent antibody - WBC white blood cell(s)     

Pharmacokinetics of ibafloxacin following intravenous and oral administration to healthy Beagle dogs

The pharmacokinetics of ibafloxacin, a new veterinary fluoroquinolone antimicrobial agent, was studied following intravenous (i.v.) and oral administration to healthy dogs. The mean absolute bioavailability of ibafloxacin after oral doses of 7.5, 15 and 30 mg/kg ranged from 69 to 81%, indicating that ibafloxacin was well absorbed by dogs. Ibafloxacin was also absorbed rapidly [time of maximum concentration (t(max)) 1.5 h], reaching a mean maximum concentration (C(max)) of 6 microg/mL at 15 mg/kg, well distributed in the body [large volume of distribution at steady state (V(ss)) and V(area) of 1.1 L/kg and 4 L/kg, respectively], and exhibited an elimination half-life of 5.2 h and a low total body clearance (8.7 mL/min/kg). Both C(max) and area under the concentration-time curve (AUC) showed dose proportionality over the dose range tested (7.5-30 mg/kg). The pharmacokinetics of ibafloxacin was similar following single and repeated dosage regimens, implying no significant accumulation in plasma. Food promoted the absorption of ibafloxacin by increasing C(max) and AUC, but did not change t(max). High amounts of the metabolites, mainly 8-hydroxy- and, 7-hydroxy-ibafloxacin were excreted in urine and faeces, either unchanged or as glucuronide conjugates. Following oral administration of 15 mg ibafloxacin/kg, the total recovery of ibafloxacin, its metabolites and conjugates in urine and faeces was 61.9-99.9% of the dose within 48 h.     

Acute response of urine pH following ammonium chloride administration to dogs

To test the acidifying ability of the distal portion of the nephrons in healthy dogs, 0.2 g of NH4Cl/kg of body weight was given PO. Samples for venous blood gas analysis and urine pH were taken hourly for 6 hours. Systemic acidemia developed, as evidenced by a statistically significant (P less than 0.05) decrease in blood pH 1 hour after NH4Cl administration. Four hours after administration, mean urine pH decreased to a low of 5.16 +/- 0.1 and was less than 5.5 3 hours after administration. Changes in urine pH 2 hours after administration were statistically significant (P less than 0.05). In human beings, NH4Cl loading is used to detect patients with distal renal tubular acidosis (defective hydrogen ion secretion by the distal nephrons) and normal acid/base values. Distal renal tubular acidosis is diagnosed if urine pH fails to decrease to less than 5.5 after NH4Cl administration. On the basis of the findings of this study, a similar value would be valid for dogs.     

Pharmacokinetics and preliminary observations of behavioral changes following administration of midazolam to dogs

The pharmacokinetics of midazolam were investigated following intravenous and intramuscular administration of 0.5 mg of midazolam hydrochloride/kg of body weight to five healthy mixed-breed dogs. One dog also received the same dose of midazolam by oral and rectal routes. The disposition of midazolam following intravenous administration was characterized by very rapid and relatively extensive distribution followed by rapid elimination. Mean (+/- SD) apparent volume of distribution was 3.0 +/- 0.9 l/kg, mean elimination half-life was 77 +/- 18 min, and clearance was 27 +/- 3 ml/kg/min. Following intramuscular administration, absorption was rapid and complete. A mean peak midazolam concentration of 549 +/- 121 ng/ml was reached within 15 min, and systemic availability was over 90% in each dog. Oral administration to one dog resulted in peak midazolam concentrations within 10 min and a systemic availability of 69%. Rectal administration to the same dog yielded very low systemic availability. Midazolam was extensively bound to canine plasma proteins, with the unbound fraction representing less than 4% of the total plasma midazolam concentration. Plasma samples were also assayed for the presence of the major metabolites, 1-OH and 4-OH midazolam. Neither metabolite were detected, probably as a result of rapid elimination of these compounds by hepatic glucuronidation. Behavioral responses to administration of midazolam included initial signs of profound weakness, ataxia and transient agitation followed by a period of quiesence. A normal behavior pattern returned within 2 h of midazolam administration.     

Serum levels and pharmacokinetics of ticarcillin and clavulanic acid in dog following parenteral administration of Timentin®

The serum concentration-time data for ticarcillin (TICAR) and clavulanic acid (CLA) following intravenous and intramuscular administration of Timentin (TICAR, 50 mg/kg with CLA, 1.7 mg/kg) indicated that absorption of CLA following intramuscular injection and its overall elimination from the body was faster than that of TICAR. This is supported by comparison of certain pharmacokinetic parameters for TICAR and CLA. These include the shorter value of Tmax for CLA (11.45 +/- 1.60 min) than that for TICAR (29.93 +/- 1.94 min) and significant variation in the elimination rate constants (0.183 +/- 0.0018 min -1 for CLA vs. 0.0097 +/- 0.0006 min -1 for TICAR) for the intravenous group of animals. The biological half-life of CLA (approximately 39 min) was significantly shorter (P less than 0.01) than that of TICAR (approximately 73 min). In spite of initial faster absorption, the intramuscular bioavailability of CLA (65.02%) was less than that of TICAR (91.37%). Though the pharmacokinetic behaviour of TICAR and CLA is not similar, yet based on the therapeutically optimal concentrations of CLA and TICAR reached in serum, Timentin at the dose used in the present study should be effective in treating most TICAR-resistant Enterobacteriaceae infections in dogs. Timentin is not likely to be effective in the treatment of infections caused by TICAR-resistant pseudomonads, at the dose used in the present study.     

Serum feline trypsin-like immunoreactivity following administration of ceruletide to healthy cats

OBJECTIVE: To determine changes in serum feline trypsin-like immunoreactivity (fTLI) in response to administration of ceruletide to healthy cats. ANIMALS: 11 healthy cats. PROCEDURES: Serum fTLI was determined, using a radioimmunoassay, before and 10, 20, 30, 40, and 50 minutes after IM administration of ceruletide (0.3 mg/kg [0.14 mg/lb]). RESULTS: Mean +/- SD baseline serum fTLI was 23.1 +/- 4.1 mg/L. There was a statistically significant, but clinically unimportant, increase in serum fTLI 10 and 30 minutes after ceruletide administration. CONCLUSIONS AND CLINICAL RELEVANCE: In healthy cats, administration of ceruletide induced a statistically significant, but clinically unimportant, increase in serum fTLI. Whether responses in cats with exocrine pancreatic disorders would be different is unknown, but results suggest that a ceruletide stimulation test would likely not be useful for differentiating between healthy cats and cats with subclinical chronic exocrine pancreatic disorders.     

Drug plasma levels following administration of trimethoprim and sulphonamide combinations to broilers

Trimethoprim (TMP) was administered in combination with either sulphadiazine or sulphadimidine to broilers, and plasma concentrations were determined simultaneously by newly developed thin-layer and/or high-performance liquid-chromatographic procedures, which also allowed quantification of the N4-acetyl metabolites of the sulphonamides. After i.v. injection of TMP (20 mg/kg body wt) and sulphadiazine (100 mg/kg body wt), both compounds were rapidly eliminated from plasma with half-lives of 1 and 2.7 h, respectively. Apparent volumes of distribution (3.3 and 0.96 l/kg, respectively) indicated that the tissue distribution of TMP was more extensive than that of the sulphonamide. After oral administration of the same dosages, elimination appeared to be slower compared to the i.v. injection, but this was obviously related to delayed absorption. Bioavailability after oral administration was approximately 100% of sulphadiazine, but only about 60% for TMP. Oral dosing of TMP in combination with sulphadimidine yielded similar maximum plasma concentrations of both compounds to those obtained with the combination of TMP with sulphadiazine, but the plasma concentration decline of sulphadimidine appeared to be more rapid than that of sulphadiazine after oral administration. During prolonged administration of different dosages of TMP-sulphadiazine combinations via drinking water, only low plasma concentrations were attained by the recommended dosage of the combination. Up to 10-fold higher dosages were tolerated by the animals without side-effects. In view of the fact that the sensitivity of bacterial strains to TMP-sulphonamide combinations differs widely, the plasma concentrations determined in the present study during prolonged drinking-water medication with different dosages of a TMP-sulphadiazine combination can be used to select effective doses for treatment of different poultry diseases.     

Serum leptin and ghrelin levels in response to methylprednisolone injection in healthy dogs

The aim of this study was to investigate the effects of methylprednisolone treatment on serum leptin and ghrelin levels in healthy dogs (n=40). After 14 h of fasting, the dogs were injected intramuscularly with saline (control group) or methylprednisolone (1, 5 or 10mg/kg). Blood samples were collected prior to (baseline) and 2, 3, 4, 8, 12 and 24h subsequent to the treatments. Serum leptin and ghrelin were measured by radioimmunoassay. The mean baseline serum leptin and ghrelin were 2.5+/-0.1 ng/mL (n=40) and 35.0+/-2.1 pg/mL (n=40), respectively. In the control dogs, serum leptin, but not ghrelin levels showed a significant fluctuation during the 24h observation period. Serum leptin increased significantly (p<0.05-0.01) between 2 and 12h after 1mg/kg of methylprednisolone. Serum leptin levels showed biphasic response to 5mg/kg of methylprednisolone: its level decreased to 1.9+/-0.1 ng/mL (p<0.01) at 2h and increased at 12h (2.6+/-0.1 ng/mL) (p<0.01). In response to 10mg/kg of methylprednisolone, serum leptin levels decreased significantly (p<0.01) for 24h. Serum ghrelin levels decreased to 19+/-5 pg/mL at 2-3h (p<0.01) or increased to 87+/-18 pg/mL at 3-8h (p<0.05-0.01) after 1mg/kg of methylprednisolone or 10mg/kg of methylprednisolone, respectively. Serum ghrelin levels did not change at any time point during 24h observation period after 5mg/kg of methylprednisolone. There was a significant (p<0.001) inverse correlation (r=-0.635) between serum leptin and ghrelin levels. In conclusion, we found that methylprednisolone increases or decreases serum leptin and ghrelin levels depending upon its dose and there is a negative correlation between serum leptin and ghrelin levels after methylprednisolone administration.     

Comparison of plasma benzodiazepine concentrations following intranasal and intravenous administration of diazepam to dogs

OBJECTIVE: To determine whether plasma concentrations of benzodiazepines (BDZ) in dogs following intranasal (IN) administration of diazepam are comparable to concentrations following IV administration. ANIMALS: 6 (4 male, 2 female) healthy adult Greyhounds. PROCEDURE: Dogs were randomly assigned to 2 groups of 3 dogs in a crossover design. Diazepam (0.5 mg/kg of body weight) was administered intravenously to dogs in group 1 and intranasally to dogs in group 2. Blood was collected from the jugular vein of each dog into tubes containing lithium heparin before and 3, 6, 9, 12, 15, 20, 30, 60, 120, 240, and 480 minutes following diazepam administration. After a 4-day washout period, dogs in group 1 received diazepam intranasally, dogs in group 2 received diazepam intravenously, and blood was again collected. Plasma concentration of BDZ was determined by use of a fluorescence polarization immunoassay. RESULTS: Mean (+/- SD) peak plasma concentration of BDZ following IV administration (1,316 +/- 216 microg/L) was greater than that following IN administration (448 +/- 41 microg/L). Time to peak concentration was < or = 3 minutes following IV administration and 4.5 +/- 1.5 minutes following IN administration. Mean bioavailability of BDZ following IN administration was 80 +/- 9%. CONCLUSIONS AND CLINICAL RELEVANCE: Diazepam is rapidly and efficiently absorbed following IN administration of the parenteral formulation. Plasma concentrations match or exceed the suggested therapeutic concentration (300 microg/L). Intranasal administration of diazepam may be useful for treatment of seizures in dogs by owners or when intravenous access is not readily available.     

Serum and tissue fluid norfloxacin concentrations after oral administration of the drug to healthy dogs

Norfloxacin, a 4-quinolone antibiotic, was administered orally to 4 healthy dogs at dosages of 11 and 22 mg/kg of body weight, every 12 hours for 4 days, with a 4-week interval between dosing regimens. Serum and tissue cage fluid (TCF) norfloxacin concentrations were measured at 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hours after the first and seventh dose of each dosing regimen. When administered at a dosage of 11 mg/kg, the mean peak serum concentration (Cmax) was 1.0 microgram/ml at 1 hour, the time of mean peak concentration (Tmax) after the first dose. After the seventh dose, the Cmax was 1.4 micrograms/ml at Tmax of 1.5 hours. The Tmax for the TCF concentration was 5 hours, with Cmax of 0.3 microgram/ml and 0.7 microgram/ml after the first and seventh dose, respectively. When administered at a dosage of 22 mg/kg, the serum Tmax was 2 hours after the first dose, with Cmax of 2.8 micrograms/ml. After the seventh dose, the serum Tmax was 1.5 hours, with Cmax of 2.8 micrograms/ml. The Tmax for the TCF concentration was 5 hours after the first and seventh doses, with Cmax of 1.2 micrograms/ml and 1.6 micrograms/ml, respectively. After the seventh dose, the serum elimination half-life was 6.3 hours for a dosage of 11 mg/kg and was 6.7 hours for a dosage of 22 mg/kg. For serum concentration, the area under the curve from 0 to 12 hours (AUC0----12) was 8.77 micrograms.h/ml and 18.27 micrograms.h/ml for dosages of 11 mg/kg and 22 mg/kg, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma levels following administration of sodium meclofenamate by various routes.

Sodium meclofenamate, an anti-inflammatory and anti-anaphylactic agent, was administered to cattle intravenously, orally and by intraruminal injection. Plasma levels of the free drug were estimated fluorimetrically at intervals after administration by each route. Levels fell rapidly, particularly during the first hour after intravenous injection. Differences between those plasma levels resulting from oral administration and those following intraruminal injection indicated that direct passage into the abomasum was achieved by the former method. Simultaneous intravenous and intrauminal injections achieved immediate high plasma levels and maintained levels adequate for efficacy for 24 h.     

C-reactive protein as an indicator of inflammatory responses to experimentally induced cystitis in dogs

The aim of this study was to demonstrate and assess C-reactive protein (CRP) changes in dogs with induced bacterial cystitis with or without antibiotics. We also evaluated availability of CRP levels to serve as an indicator for monitoring or diagnosing bacterial cystitis. Serial CRP concentrations in dogs with induced bacterial cystitis were higher than those of controls (p < 0.001). CRP concentrations peaked on day 7 and gradually decreased thereafter. In the treatment group, CRP concentrations decreased after medication compared to the untreated group (p = 0.032). CRP levels had a linear correlation with urine white blood cell counts among all groups (r = 0.837, p < 0.001, n = 140). Compared to the negative urine culture group, dogs with positive urine culture results had higher CRP concentrations (median 43.8 mg/L vs. 5.9 mg/L; p < 0.001). Area under the receiver operating characteristic curve was 0.955; when cut-off value was 12.2 mg/L, CRP measurements were found to have a sensitivity of 92.3% and specificity of 86.4%. This result indicates that rapid increases of CRP occurred after inducing bacterial cystitis and CRP may be a useful indicator for monitoring or diagnosing canine bacterial cystitis together with sediment urinalysis and urine bacterial culture.     

Pharmacokinetics of buprenorphine following intravenous and oral transmucosal administration in dogs

Pharmacokinetic analysis of buprenorphine administered to six healthy dogs via the oral transmucosal (OTM) route at doses of 20 and 120 microg/kg was conducted using liquid chromatography-electrospray ionization-tandem mass spectroscopy (LC-ESI-MS/MS). Bioavailability was 38% plus or minus 12% for the 20 microg/kg dose and 47%+/-16% for the 120 microg/kg dose. Maximum plasma concentrations were similar for buprenorphine doses of 20 microg/kg IV and 120 microg/kg OTM. Sedation and salivation were common side effects, but no bradycardia, apnea, or cardiorespiratory depressive effects were seen. When the two OTM dosing rates were normalized to dose, LC-ESI-MS/MS analysis of buprenorphine and its metabolites detected no significant difference (P>.05), indicating dose proportionality. The results of this study suggest that OTM buprenorphine may be an alternative for pain management in dogs.