Browsing by Author "Coskun D."

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Effect of ketoprofen and tolfenamic acid on intravenous pharmacokinetics of ceftriaxone in sheep
(2021-11-01) Cetin G.; Durna Corum D.; Corum O.; Atik O.; Coskun D.; Uney K.
In this study, the pharmacokinetics of ceftriaxone (40 mg/kg) was determined following a single intravenous (IV) administration of ceftriaxone alone and co-administration with ketoprofen (3 mg/kg) or tolfenamic acid (2 mg/kg) in sheep. Eight healthy Akkaraman sheep (2.4 ± 0.3 years and 44 ± 4 kg of body weight) were used. The study was carried out according to the longitudinal design in three periods with a 15-day washout period between administrations. In the first period, sheep received ceftriaxone alone via an IV injection. In the second and third periods, the same sheep received ceftriaxone in combination with ketoprofen and tolfenamic acid, respectively. Plasma concentrations of ceftriaxone were assayed by high-performance liquid chromatography and analyzed using non-compartmental analysis. Following the administration of ceftriaxone alone, the elimination half-life (t1/2ʎz), area under the plasma concentration–time curve from zero (0) hours to infinity (∞) (AUC0-∞), total clearance (ClT), and volume of distribution at steady state were 1.42 h, 182.41 h*µg/ml, 0.22 L/h/kg, and 0.17 L/kg, respectively. While ketoprofen and tolfenamic acid significantly increased the t1/2ʎz and AUC0-∞ of ceftriaxone, they significantly reduced the ClT. Ceftriaxone (40 mg/kg, IV) in concurrent use with ketoprofen and tolfenamic acid can be administrated at the 12 h dosing intervals to maintain T> minimum inhibitory concentration (MIC) values above 60% in the treatment of infections caused by susceptible pathogens with the MIC value of ≤0.75 and ≤1 μg/mL, respectively, in sheep with an inflammatory condition.
Effect of ketoprofen on intravenous pharmacokinetics of ganciclovir in chukar partridges (Alectoris chukar)
(2022-01-01) Corum O.; Uney K.; Durna Corum D.; Atik O.; Coskun D.; Zhunushova A.; Elmas M.
The aim of the study was to determine the effect of ketoprofen (2 mg/kg) on the intravenous pharmacokinetics of ganciclovir (10 mg/kg) in chukar partridges (Alectoris chukar). Eight clinically healthy partridges were used in the study. The study was performed in two periods using a cross-over design following a 15-day drug washout period. Plasma concentrations of ganciclovir were determined using the high-pressure liquid chromatography-ultraviolet detector and analyzed by non-compartmental analysis. The elimination half-life (t1/2ʎz), area under the concentration-time curve (AUC0-∞), total body clearance, and volume of distribution at steady state of ganciclovir were 1.63 h, 33.22 h*μg/ml, 0.30 L/h/kg, and 0.53 L/kg, respectively. Ketoprofen administration increased the t1/2ʎz and AUC0-∞ of ganciclovir by 78% and 108%, respectively, and while decreased ClT by 53%. The increased plasma concentration and prolonged elimination half-life of ganciclovir caused by ketoprofen may result in the prolonged duration of action and therapeutic effect of ganciclovir. However, the concomitant use requires determination of the pharmacokinetics of ketoprofen and the safety of both drugs.
Effect of supportive therapy on the pharmacokinetics of intravenous marbofloxacin in endotoxemic sheep
(2020-05-01) Coskun D.; Corum O.; Yazar E.
The purpose of this study was to determine the influences of supportive therapy (ST) on the pharmacokinetics (PK) of marbofloxacin in lipopolysaccharide (LPS)-induced endotoxemic sheep. Furthermore, minimum inhibitory concentration (MIC) of marbofloxacin against Escherichia coli, Mannheimia haemolytica, Pasteurella multocida, Klebsiella pneumoniae, Salmonella spp., and Staphylococcus aureus was determined. The study was performed using a three-period cross PK design following a 15-day washout period. In the first period, marbofloxacin (10 mg/kg) was administered by an intravenous (IV) injection. In the second and third periods, marbofloxacin was co-administered with ST (lactated ringer + 5% dextrose + 0.45% sodium chloride, IV, 20 ml/kg, dexamethasone 0.5 mg/kg, SC) and ST + LPS (E. coli O55:B5, 10 µg/kg), respectively. Plasma marbofloxacin concentration was measured using HPLC-UV. Following IV administration of marbofloxacin alone, the (Formula presented.), AUC0–∞, ClT, and Vdss were 2.87 hr, 34.73 hr × µg/ml, 0.29 L hr−1 kg−1, and 0.87 L/kg, respectively. While no change was found in the MBX + ST group in terms of the PK parameters of marbofloxacin, it was determined that the ClT of marbofloxacin decreased, AUC0–∞ increased, and (Formula presented.) and MRT prolonged in the MBX + ST + LPS group. MIC values of marbofloxacin were 0.031 to >16 µg/ml for E. coli, 0.016 to >16 µg/ml for M. haemolytica, 0.016–1 µg/ml for P. multocida, 0.016–0.25 µg/ml for K. pneumoniae, 0.031–0.063 µg/ml for Salmonella spp., and 0.031–1 µg/ml for S. aureus. The study results show the necessity to make a dose adjustment of marbofloxacin following concomitant administration of ST in endotoxemic sheep. Also, the PK and pharmacodynamic effect of marbofloxacin needs to be determined in naturally infected septicemic sheep following concomitant administration of single and ST.
Effects of Temperature on the Pharmacokinetics, Tissue Residues, and Withdrawal Times of Doxycycline in Rainbow Trout (Oncorhynchus mykiss) following Oral Administration
(2023-06-01) Corum O.; Uney K.; Terzi E.; Durna Corum D.; Coskun D.; Altan F.; Elmas M.
The purpose of this study was to compare the pharmacokinetics, tissue residues, and withdrawal times of doxycycline after oral administration in rainbow trout reared at 10 and 17 °C. Fish received a 20 mg/kg oral dose of doxycycline after a single or 5-day administration. Six rainbow trout were used at each sampling time point for plasma and tissue samples, including liver, kidney, and muscle and skin. The doxycycline concentration in the samples was determined using high-performance liquid chromatography with ultraviolet detector. The pharmacokinetic data were evaluated by non-compartmental kinetic analysis. The WT 1.4 software program was used to estimate the withdrawal times. The increase of temperature from 10 to 17 °C shortened the elimination half-life from 41.72 to 28.87 h, increased the area under the concentration–time curve from 173.23 to 240.96 h * μg/mL, and increased the peak plasma concentration from 3.48 to 5.50 μg/mL. At 10 and 17 °C, the doxycycline concentration was obtained in liver > kidney > plasma > muscle and skin. According to the MRL values stated for muscle and skin in Europe and China (100 μg/kg) and in Japan (50 μg/kg), the withdrawal times of doxycycline at 10 and 17 °C were 35 and 31 days, respectively, for Europe and China and 43 and 35 days, respectively, for Japan. Since temperature significantly affected pharmacokinetic behavior and withdrawal times of doxycycline in rainbow trout, temperature-dependent dosing regimens and withdrawal times of doxycycline might be necessary.
Pentoxifylline may restore kanamycin-induced renal damage in rats
(2018-01-01) Corum O.; Ozdemir O.; Hitit M.; Corum D.D.; Coskun D.; Er A.
Background: Kidney damage can be caused by many factors, such as using certain drugs in high doses or over the long term. The use of one such group of drugs, aminoglycosides, which act as Gram-negative antibacterial therapeutic agents, can lead to nephrotoxicity. It has been hypothesized that aminoglycoside-induced nephrotoxicity might be prevented by using pentoxifylline, which has antioxidant and anti-inflammatory effects and improves microcirculation. The objective of this present research was to determine the protective effects of pentoxifylline on kanamycin-induced kidney damage. Materials, Methods & Results: Thirty-two male Wistar rats were divided into four groups as follows: control, pentoxifylline, kanamycin, and kanamycin + pentoxifylline. The control group received intraperitoneal (IP) injections of 0.5 mL normal saline solution once a day (d) (SID) for 20 d; the pentoxifylline group received IP injections of 50 mg/kg pentoxifylline twice a day (BID) for 20 d, the kanamycin group received subcutaneous (SC) injections of 500 mg/kg kanamycin SID for 20 d, and the kanamycin + pentoxifylline group received both SC injections of 500 mg/kg kanamycin SID and IP injections of 50 mg/kg pentoxifylline BID for 20 d. At the end of 20 d, blood samples were taken from the heart by cardiac puncture under general anesthesia. After euthanizing the rats by cervical dislocation under anesthesia, the kidneys were immediately removed, relative kidney weights were calculated, and routine pathologic evaluations were conducted. Hemogram parameters were measured using a blood cell count apparatus and serum biochemical parameters were measured using an autoanalyzer. Kanamycin also caused (P < 0.05) tubular degeneration and tubular dilatation. Although pentoxifylline significantly reduced the level of kanamycin-induced tubular degeneration (P < 0.05), it did not significantly reduce tubular dilatation. Increases in relative kidney weights (P < 0.05) and in interstitial mononuclear cell (MNC) infiltrates were observed in the kanamycin and kanamycin + pentoxifylline groups compared to those in the control and pentoxifylline groups. Statistically significant changes were determined in the levels of some hemogram and biochemical parameters within reference ranges (P < 0.05). Discussion: In this study, both tubular degeneration and dilatation were observed in the kanamycin group. Pentoxifylline inhibited (P < 0.05) kanamycin-induced tubular degeneration and appeared to also reduce tubular dilatation, although this reduction was not significant. Tubular necrosis, epithelial edema of proximal tubules, tubular fibrosis, and perivascular inflammation might also be observed in aminoglycoside-induced nephrotoxicity. In current research, pentoxifylline prevented tubular damage induced by kanamycin, but did not inhibit infiltration by MNCs. Pentoxifylline also ameliorated amikacin- or gentamycin-induced histopathologic changes, especially those associated with tubular structures. The protective effects of pentoxifylline on kanamycin-induced tubular nephrotoxicity in this research might be a result of its stimulating the production of prostaglandin, a vasodilator, and of its improving microcirculation. Although the anti-inflammatory effects of pentoxifylline have been reported, these did not inhibit kanamycin-induced infiltration by interstitial MNCs in the present study. These results could indicate that the anti-inflammatory effects of pentoxifylline are not obvious and/or are dose dependent. Statistically significantly changes were determined in the levels of some hemogram and biochemical parameters in reference ranges. However, these changes were within the reference ranges for rats. These results suggested that kanamycin-induced tubular degeneration and dilatation might be prevented by administering pentoxifylline.
Pharmacokinetics of cefquinome in rainbow trout (Oncorhynchus mykiss) after intravascular, intraperitoneal, and oral administrations
(2022-11-01) Durna Corum D.; Corum O.; Terzi E.; Coskun D.; Bilen S.; Cetin G.; Uney K.
This study aimed to determine the pharmacokinetics and bioavailability of cefquinome in rainbow trout (Oncorhynchus mykiss) following intravascular (IV), intraperitoneal (IP), and oral (PO) administrations at 14 ± 1°C. In this study, three hundred and six clinically healthy rainbow trout (110–140 g) were used. The fish received single IV, IP, and PO injections of cefquinome at 10 mg/kg dose. The plasma concentrations of cefquinome were measured using HPLC-UV and were evaluated using non-compartmental analysis. Cefquinome was measured up to 96 h for PO route and 144 h for IV and IP routes in plasma. Following IV administration, t1/2ʎz, ClT, and Vdss were 18.85 h, 0.037 L/h/kg, and 0.84 L/kg, respectively. The Cmax of IP and PO routes was 9.75 and 1.64 μg/ml, respectively. The bioavailability following IP and PO administrations was 59.46% and 12.33%, respectively. Cefquinome at 10 mg/kg dose may maintain T > MIC above 40% at 72 and 96 h intervals, respectively, following the IP and IV routes for bacteria with MIC values of ≤2 μg/ml and at 24 h intervals following the PO route for bacteria with MIC value of ≤0.75 μg/ml. However, further studies are needed to determine in vitro and in vivo antibacterial efficacy and multiple dosage regimens of cefquinome against pathogens isolated from rainbow trout.