Umit Karademir

Effects of carprofen and meloxicam on C-reactive protein, ceruloplasmin, and fibrinogen concentrations in dogs undergoing ovariohysterectomy

OBJECTIVE To evaluate the effects of perioperative oral administration of carprofen and meloxicam on concentrations of 3 acute-phase proteins in dogs undergoing elective ovariohysterectomy (OVH). ANIMALS 18 healthy adult anestrous female dogs undergoing elective OVH. PROCEDURES Dogs were allocated to 3 groups (6 dogs/group). A placebo treatment, carprofen (2.0 mg/kg), or meloxicam (0.2 mg/kg) was orally administered to the dogs of the respective groups. The initial doses were administered 30 minutes before premedication prior to OVH; additional doses were administered once daily for 4 days after surgery. Blood samples were collected 45 minutes before premedication and 4, 8, 12, 24, 36, 48, 72, 96, and 120 hours after the end of OVH; samples were used for measurement of total WBC and neutrophil counts and concentrations of C-reactive protein (CRP), ceruloplasmin, and fibrinogen. RESULTS Values did not differ significantly among groups for WBC and neutrophil counts, serum concentrations of CRP and ceruloplasmin, and plasma concentrations of fibrinogen. Concentrations of all inflammatory markers, except serum ceruloplasmin, increased significantly following OVH, but in a similar manner for each group. No significant changes were detected in serum ceruloplasmin concentrations over time. CONCLUSIONS AND CLINICAL RELEVANCE Perioperative administration of both carprofen and meloxicam did not significantly affect the concentrations of CRP, ceruloplasmin, and fibrinogen in dogs undergoing OVH. Thus, use of carprofen or meloxicam should not affect clinical interpretation of results for these 3 acute-phase proteins.

The effect of sesame and sunflower oils on the plasma disposition of ivermectin in goats

The effect of sesame oil (SSO) and sunflower oil (SFO) (the excipients) on the plasma disposition of ivermectin (IVM) following intravenous (i.v.) and subcutaneous (s.c.) administration at a dosage of 200 microg/kg was investigated in goats. Ten clinically healthy crossbred goats were used in the study. The animals were allocated by weight and sex into two groups of five animals each. Group 1 (n = 5) received the drug and excipient by the i.v. route only and group 2 received drug and excipient by the s.c. route only. The study was designed according to a two-phase crossover design protocol. In the first phase three animals in group 1 were i.v. administered IVM (0.2 mg/kg) + SSO (1 mL) and the other two animals received IVM (0.2 mg/kg) + SFO (1 mL). In the second phase animals were crossed over and received the alternate excipient with IVM at the same dosages. In group 2 during the first phase, three animals were s.c. administered IVM (0.2 mg/kg) + SSO (1 mL) and the other two animals were received IVM (0.2 mg/kg) + SFO (1 mL). In the second phase animals were crossed over and received the alternate excipient with IVM at the same dosages. A 4-week washout period was allowed between the two phases. In group 2 significantly increased dermal thickness was observed at the s.c. injection site of the all animals which received IVM during phase I regardless of the excipient. There was almost no change observed at the injection site of any animal during the second phase of the study following s.c. administration. In group 2 the plasma concentrations of IVM in the second phase for both excipient combinations were much higher than the plasma concentrations following first administration and appeared to be related with the dermal changes. The mean plasma disposition of IVM in combination with SSO or SFO was similar following i.v. administration. Longer terminal elimination half-lives and resultant longer mean resident time were observed after s.c. administration of the both combinations compared with i.v. administration.

Plasma disposition of enrofloxacin following intravenous and intramuscular administration in donkeys

This study was designed to investigate the plasma disposition and systemic availability of enrofloxacin (ENR) following intramuscular and intravenous administrations. Six donkeys (Equus asinus) were used in this study. The animals were allocated into two groups (intramuscular and intravenous groups). After a 2-week washout period, the experiment was repeated with the groups reversed according to a two-phase crossover design. In phase I, group I received intravenously the commercially available injectable solution of ENR at the dose of 5 mg/kg and group II received intramuscularly the same ENR formulation at the same dose rate. Blood samples were collected 1 hour prior to drug administration and various times between 5 minutes and 48 hours post-treatments. The samples were analysed by high performance liquid chromatography with fluorescence detector. The half-life and mean residence time of ENR (12.08 hours and 17.85 hours) after intramuscular route were significantly longer compared with intravenous administration (9.54 hours and 7.46 hours, respectively) and these were associated with a flip-flop phenomenon. A marked proportion of ENR (20–21 per cent) was metabolised to ciprofloxacin (CPR) following both administration routes and the half-life of CPR paralleled that of the parent drug after intramuscular administration. Mean absorption time was relatively long (10.39 hours), and the bioavailability of ENR was 76.56 per cent after intramuscular route in the donkeys. The plasma concentration is lower after intramuscular administration at a dose rate of 5 mg/kg, and may need a higher dose to provide sufficient plasma concentration in donkeys compared with horses.

The effect of fasting on the plasma disposition of triclabendazole following oral administration in goats

This study was designed to investigate the effect of feeding on the plasma disposition of triclabendazole (TCBZ) in goats following oral administration. A total of eight goats, aged 14-16 months and weighing 20-30 kg were used in this study. The animals were allocated into two groups (fasted and fed groups) of four animals each. The goats in fed group were fed ad libitum but the animals in fasted group were not fed 24 h before and 6 h after drug administration. Commercial oral drench formulation of TCBZ (Endex-K, 5%) was administered orally to animals in two groups at dose of 10mg/kg bodyweight. Heparinized blood samples were collected between 1 and 192 h after treatment and the plasma samples were analysed by high performance liquid chromatography (HPLC) for TCBZ, TCBZ sulphoxide (TCBZ-SO), and TCBZ sulphone (TCBZ-SO(2)). Relatively very low concentration of TCBZ parent drug was detected between 2 and 48 h, but TCBZ-SO and TCBZ-SO(2) metabolites were present between 2 and 192 h in the plasma samples of fed and fasted animals. Fasting significantly enhanced the plasma concentration of TCBZ and its metabolites. The availability of TCBZ, TCBZ-SO and TCBZ-SO(2) in the plasma samples of fasted goats were markedly greater compared to those of fed goats. It was concluded that fasting decreases the digesta flow rate and prolongs the retention of the drug into the gastrointestinal tract, resulting in enhanced quantitative gastrointestinal absorption or systemic availability of TCBZ and its metabolites in fasted goats.

Pharmacokinetics of meloxicam in adult goats: a comparative study of subcutaneous, oral and intravenous administration

Abstract AIMS: To determine the plasma disposition of meloxicam in goats following S/C, oral or I/V administration at a single dose of 0.5 mg/kg bodyweight. METHODS: Five healthy Saanen goats, aged 12–14 months and weighing 35–40 kg, were used for a three phase cross-over design with a 10-day washout period, with meloxicam administered I/V, then orally and S/C. Heparinised blood samples (5 mL) were collected from all animals prior to drug administration (0 hours) and subsequently up to 96 hours. Concentrations of meloxicam in plasma were measured using high performance liquid chromatography. Concentration-time curves were fitted and pharmacokinetic parameters were estimated for each administration group. RESULTS: Subcutaneous administration of meloxicam exhibited unique plasma distribution characteristics that differed from oral and I/V administration. Mean peak plasma concentrations were greater (1.91 (SD 0.39) vs. 0.71 (SD 0.17) µg/mL) and the time to reach them shorter (3.20 (SD 1.64) vs. 14.33 (SD 2.19) hours) following S/C compared with oral administration (p<0.05). The terminal half-life was longer (15.16 (SD 4.74) vs. 10.69 (SD 1.49) hours) and the MRT was shorter (15.67 (SD 2.37) vs. 24.33 (SD 3.12) hours) following S/C than oral administration (p<0.05), but bioavailability was similar (98.24 (SD 9.62) vs. 96.49 (SD 10.71)%). CONCLUSION AND CLINICAL RELEVANCE: Subcutaneous administration of meloxicam resulted in long-term presence of drug at high concentration in goat plasma. This unique plasma disposition characteristic may offer an advantage in some clinical cases towards potentially improving the treatment efficacy in goats.

Evaluation of the Effect of Ketoprofen on Haemostatic Parameters in Holstein Heifers Following Dehorning

Aril propiyonik asit turevi olan Ketoprofen (KTP) secici olmayan guclu bir siklooksijenaz (COX) inhibisyonu ile nonsteroidal anti-inflammatuar ilaclar arasindadir. KTP sigirlarda boynuzsuzlastirma agrisini hafifletir. Sigirlarin pihtilasma ozellikleri hemostatik degisiklikler veya fonksiyon bozuklularini onlemek amaciyla ameliyat oncesi dikkate alinmalidir. Bu calismada boynuzsuzlastirma islemi uygulanan duvelerde KTP’nin koagulasyon profillerine olan etkisi degerlendirildi. Duvelere (n=7) boynuzsuzlastirma oncesi KTP (2.2 mg/kg i.v.) tek doz uygulandi. Fibrinojen (F), protrombin zamani (PT) ve active edilmis parsiyel tromboplastin zamani (APTT) uygulama oncesi (0.), 30., 60. ve 90 dakikalarda belirlendi. Ortalama degerler (±SD) dikkate alindiginda, PT degerleri baslangic degerlerinin aksine 30. dakikada belirgin bir artis oldu (PKetoprofen (KTP), an aryl propionic acid derivative, is a nonsteroidal anti-inflammatory drug (NSAID) with the potential of a strong non-selective inhibition of cyclooxygenase (COX). KTP mitigates dehorning pain in cattle. The coagulation status of the cattle has to be taken in to consideration prior to surgery in an attempt to prevent haemostatic alterations or dysfunction. In this study, the effect of administration of KTP on the coagulation profiles of Holstein heifers subjected to dehorning is evaluated. Heifers (n=7) were treated with KTP (2.2 mg/kg i.v.) for a single dose prior to dehorning. Fibrinogen (Fb), prothrombin time (PT), activated partial thromboplastin time (APTT) were determined prior to administration (0.) and 30, 60 and 90 minutes later. Taking into account the mean values (±SD) obtained, the PT was significantly increased on 30. minutes in contrast to initial values (P<0.05). Similarly, Fb concentration showed statistical significance on 60. minutes (P<0.05) in comparison to the initial values. Significant differences were not detected in other coagulation panel parameters at sampling times. In conclusion, i.v. administration of KTP at a single dose in heifers subjected to dehorning causes slight changes of selected haemostatic variables. KTP only caused elevations on PTT and Fb. Based on these results, when KTP is used in cattle before surgery for its analgesic effect, it should cause alterations on the haemostatic properties during the dehorning.