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    Effect of ketoprofen and tolfenamic acid on intravenous pharmacokinetics of ceftriaxone in sheep
    (Wiley, 2021) Cetin, Gul; Durna Corum, Duygu; Corum, Orhan; Atik, Orkun; Coskun, Devran; Uney, Kamil
    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 (t(1/2 lambda z)), area under the plasma concentration-time curve from zero (0) hours to infinity (infinity) (AUC(0-infinity)), total clearance (Cl-T), and volume of distribution at steady state were 1.42 h, 182.41 h*mu g/ml, 0.22 L/h/kg, and 0.17 L/kg, respectively. While ketoprofen and tolfenamic acid significantly increased the t(1/2 lambda z) and AUC(0-infinity) of ceftriaxone, they significantly reduced the Cl-T. 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 mu g/mL, respectively, in sheep with an inflammatory condition.
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    Öğe
    Effect of ketoprofen on intravenous pharmacokinetics of ganciclovir in chukar partridges (Alectoris chukar)
    (Wiley, 2022) Corum, Orhan; Uney, Kamil; Corum, Duygu Durna; Atik, Orkun; Coskun, Devran; Zhunushova, Aidai; Elmas, Muammer
    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 (t(1/2 lambda z)), area under the concentration-time curve (AUC(0-infinity)), total body clearance, and volume of distribution at steady state of ganciclovir were 1.63 h, 33.22 h*mu g/ml, 0.30 L/h/kg, and 0.53 L/kg, respectively. Ketoprofen administration increased the t(1/2 lambda z) and AUC(0-infinity) of ganciclovir by 78% and 108%, respectively, and while decreased Cl-T 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.