J vet Pharmacol Therap. 2019;42:207–213. wileyonlinelibrary.com/journal/jvp © 2018 John Wiley & Sons Ltd
|
2071 | INTRODUCTION
Danofloxacin is a fluoroquinolone antibiotic used in veterinary medicine, which exerts its bactericidal effect by inhibiting DNA gyrase in bacteria. Danofloxacin is approved for use in chickens by the European Medicines Agency (CVMP, 2002). Danofloxacin is a broad spectrum antibiotic effective against Gram- negative and Gram- positive bacteria and mycoplasma (Nakamura, 1995; Nelson,
Chiller, Powers, & Angulo, 2007; Summa & Guzman, 2017). It has considerable pharmacokinetic (PK) characteristics, including rapid absorption following oral and parenteral administration, long elim-ination half- life, large distribution volume, good tissue penetration, and post antibiotic effect (Walker, 2000). It has a higher oral bioavail-ability in Japanese quails and pheasants than enrofloxacin (Summa & Guzman, 2017). Danofloxacin has been found to be the effective for the treatment of infections caused by Mycoplasma gallisepticum Received: 10 July 2018
|
Revised: 9 October 2018|
Accepted: 25 October 2018DOI: 10.1111/jvp.12737
O R I G I N A L A R T I C L E
Pharmacokinetics and bioavailability of danofloxacin in
chukar partridge (Alectoris chukar) following intravenous,
intramuscular, subcutaneous, and oral administrations
Orhan Corum
1| Duygu Durna Corum
1| Orkun Atik
2| Hatice Eser Faki
3|
Feray Altan
3| Kamil Uney
4 1Department of Pharmacology andToxicology, Faculty of Veterinary Medicine, University of Kastamonu, Kastamonu, Turkey
2Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Afyon Kocatepe, Afyonkarahisar, Turkey
3Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Dicle, Diyarbakir, Turkey
4Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Selcuk, Konya, Turkey
Correspondence
Orhan Corum, Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Kastamonu, Kastamonu, Turkey.
Email: orhancorum46@hotmail.com
Abstract
The aim of the present study was to determine the pharmacokinetics (PKs) and bio-availability of danofloxacin in chukar partridge (Alectoris chukar) following intrave-nous (IV), intramuscular (IM), subcutaneous (SC), and oral (PO) administrations at a dose of 10 mg/kg. A total of eight clinically healthy chukar partridges weighing 480 ± 45 g were used for the investigation. The study was performed in a crossover design (2 × 2 × 2 × 2) with a 15- day washout period between two administrations in four periods. The plasma concentrations of danofloxacin were determined using reversed- phase high- performance liquid chromatography. Noncompartmental PK parameters were also estimated. No local or systemic adverse drug effects were ob-served in any of the chukar partridges. The mean elimination half- life ranged be-tween 8.18 and 12.08 hr and differed statistically among administration routes. The mean peak plasma concentrations of danofloxacin following IM, SC, and PO adminis-trations were 8.05, 9.58, and 3.39 μg/ml at 0.5, 1, and 4 hr, respectively. Following IM, SC, and PO administrations, the mean bioavailability was 86.33%, 134.40%, and 47.62%, respectively. The mean total clearance and volume of distribution at steady- state following IV administration were 0.13 L hr−1 kg−1 and 0.96 L/kg, respectively.
These data, including favorable PKs and the absence of adverse drug effects, suggest that danofloxacin is a useful antibiotic in chukar partridges.
K E Y W O R D S
(M. gallisepticum), Escherichia coli (E. coli), and Pasteurella multocida (P. multocida) (Charleston, Gate, Aitken, Stephan, & Froyman, 1998;
Jordan, Horrocks, Jones, Cooper, & Giles, 1993; Zeng et al., 2011) in chickens. These favorable PK and pharmacodynamics (PD) char-acteristics of danofloxacin suggest that it is preferred for treat-ing infections caused by sensitive pathogens in chukar partridges (Alectoris chukar).
The PKs of danofloxacin in chickens (Yang, Sun, Liu, & Zeng, 2015; Zeng et al., 2011), turkeys (Haritova, Rusenova, Parvanov, Lashev, & Fink- Gremmels, 2006), ducks (Goudah & Mouneir, 2009), pheasants, guinea fowl, and quails (Dimitrova, Haritova, Dinev, Moutafchieva, & Lashev, 2014) have been reported. As no PK investigation on chukar partridges has been reported in the lit-erature review, the present study is considered to be the first PK investigation on chukar partridges. The aims of the study were as follows: (a) to determine the PKs and bioavailability of danoflox-acin following intravenous (IV), intramuscular (IM), subcutaneous (SC), and oral (PO) administrations at a dose of 10 mg/kg dose in chukar partridges and (b) to integrate PD data reported for M.
gal-lisepticum, E. coli, and P. multocida with PK parameters obtained
in this study in order to determine the values of the PK/PD pa-rameters [area under the plasma concentration–time curve (AUC)/ minimum inhibitory concentration (MIC)] and peak plasma concen-tration (Cmax)/MIC.
2 | MATERIALS AND METHODS
2.1 | Chemicals
The analytic standard of danofloxacin (≥98%) was obtained from Sigma- Aldrich (St. Louis, MO, USA). Acetonitrile, triethylamine, and orthophosphoric acid (Merck, Darmstadt, Germany) were used at an appropriate purity for high- pressure liquid chroma-tography (HPLC). The parenteral formulation (Advocin, 25 mg/ml, injectable solution, Zoetis, Turkey) of danofloxacin mesylate was used for the IV, IM, SC, and PO administrations. The danofloxacin formulation was diluted at a concentration of 5 mg/ml in normal saline for PO administration.
2.2 | Animals
A total of eight chukar partridges with a body weight of 480 ± 45 g and that had not been exposed to any medication for the preced-ing 2 months were used in this study. The chukar partridges were purchased from a private farm (Kepez, Antalya, Turkey). The chukar partridges were housed in pairs, with each placed in a wire cage with a clean floor, and the partridges were fed with drug- free standard partridge food (Canoglu Yem, Gaziantep/Turkey). Water was pro-vided ad libitum. The study was performed following a 2- week ac-climatization period. All research protocols were approved by The Ethics Committee of the Faculty of Veterinary Medicine (University of Selcuk, Konya, Turkey).
2.3 | Experimental groups and drug administrations
The study comprised four periods, according to a crossover PK design (2 × 2 × 2 × 2) with a 15- day washout period between treatments. The chukar partridges received danofloxacin mesylate via IV, IM, SC, and PO administration at a dose of 10 mg/kg. For the IV, IM, SC, and PO routes, danofloxacin was administered through the left jugu-lar vein, pectoral muscle, lateral abdominal area, and gavage using a plastic tube, respectively. The partridges were fasted for 12 hr prior to drug administration. Blood samples (0.15–0.2 ml) were collected using an insulin injector previously washed with 0.05 ml of heparin sodium (Nevparin, Mustafa Nevzat, Istanbul, Turkey) from the right jugular vein through a catheter at the 0 hr (pre- administration) and at 0.25, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, and 48 hr following admin-istration. Subsequently, plasma samples were obtained by centrifug-ing 4,000 g of blood samples for 10 min and were preserved under −70°C until the time of analysis.2.4 | Danofloxacin analysis
The plasma concentration of danofloxacin was processed using the HPLC- UV (Shimadzu, Tokyo, Japan) system by modifying the previ-ously defined method (Potter, Illambas, Pelligand, Rycroft, & Lees, 2013; Real et al., 2011). In total, 75 μl of the partridge plasma samples was transferred to 2- ml microcentrifuge tubes, and 150 μl of acetoni-trile was added to them. The mixture was then vortexed for 30 s and centrifuged at 10,000 g for 10 min. The obtained clean supernatant was transferred to autosampler vials, and 10 μl of this was injected into the HPLC- UV system. The HPLC system contained a pump (LC- 20AT), degasser (DGU- 14A), autosampler (SIL- 20A), and column oven (CTO- 10A). Determination of danofloxacin was performed using a UV- VIS (SPD- 10A) detector under 280 nm. The autosampler was maintained under room temperature, whereas the column tem-perature was maintained at 40°C. Chromatographic separation was performed using the Gemini™ C18 column (250 × 4.6 mm; internal
diameter, 5 μm; Phenomenex, Torrance, CA, USA). The mobile phase with at flow rate of 1 ml/min consisted of acetonitrile and 0.4% or-thophosphoric acid containing 0.4% triethylamine (18:82, v/v).
The stock solution (1 mg/ml) of danofloxacin was prepared in water and was stored at −70°C. The stock solution of danofloxa-cin was diluted with water to prepare calibration standards (0.04– 40 μg/ml) and quality control (QC) samples. QC samples at the concentrations of 0.1 μg/ml (low), 1 μg/ml (medium), and 10 μg/ml (high) were prepared by spiking blank partridge plasma and used to determine the intra- and inter day precision, recovery, and accuracy of the assay.
Before performing HPLC analysis of samples, the method was validated with regard to its selectivity, linearity, sensitivity, recovery, precision (intra- and interday), and accuracy. The selectivity of the method was controlled for interference from partridge plasma. The linearity of the method was evaluated by a calibration curve in the range of 0.04–40 μg/ml danofloxacin. Sensitivity was expressed as the limit of detection (LOD), which is the plasma concentration of
danofloxacin that can be quantified by measuring a signal- to- noise ratio of at least 3:1 and the limit of quantification (LOQ), which is defined as the lowest concentration of analyte with acceptable ac- curacy and precision (<15% for each criterion). The recovery was de-termined in six replicate by extracting QC samples at low, medium, and high concentrations. The recovery was calculated by comparing the spiked concentrations with the observed concentration. The intra day and inter day accuracy and precision were determined by six replicate analyses of each level of quality control samples within 1 day or on 6 consecutive days. The precision was determined by the coefficient of variation (CV), and the accuracy is expressed as bias [Bias (%) = 100 × (calculated concentration−theoretical concen-tration)/theoretical concentration].
2.5 | PK calculations
The PK parameters were assigned by non compartmental analysis using Phoenix WinNonlin V 6.1.0.173 software (Pharsight, Certara, St. Louis, MO, USA). Elimination rate constant (λz), terminal elimina-tion half- life (t1/2ʎz), mean residence time (MRT), the area under the plasma concentration–time curve (AUC), volume of distribution at steady- state (Vdss), and total clearance (ClT) were determined. The peak plasma concentration (Cmax) and time to reach Cmax (Tmax) were assigned by direct inspection of the plasma concentration–time curve of each animal. t1/2ʎz was calculated by ln 2/λz. The AUC was estimated by the log- trapezoidal rule. The mean absorption time (MAT) was calculated as MRTIM, SC, PO−MRTIV. The bioavailability (F) following IM, SC, and PO administrations was calculated using the following formula: F = (AUCIM, SC, PO/AUCIV) × 100.
2.6 | PD calculations
The AUC0–24/MIC and Cmax/MIC ratios were calculated using the MIC values reported for M. gallisepticum, E. coli, and P. multocida, as obtained from different species of poultry animals (Cooper, Fuller, Fuller, Whittlestone, & Wise, 1993; Geornaras, Hastings, & von Holy,
2001; Haritova et al., 2006; Zeng et al., 2011; Zhang et al., 2017) and using the PK parameters obtained in present study.
2.7 | Statistical analyses
All values are presented as the mean ± (SD). Statistical differences between the administration routes in PK parameters were analyzed by one- way analysis of variance and the post hoc Tukey test. The harmonic mean was calculated for t1/2ʎz, MRT, and MAT values analyzed using Wilcoxon’s rank- sum test. The statistics software program, SPSS version 22.0 (IBM Corp, Armonk, NY, USA), was used. p < 0.05 was accepted to indicate a statistically significant difference.
3 | RESULTS
3.1 | Method validation
In plasma samples, no interferences from endogenous compounds were shown on chromatograms. The assay of calibration standards for danofloxacin was linear (>0.9997) above the concentration range of 0.04–40 μg/ml. Plasma recovery ranged between 96% and 102%. The LOD and the LOQ were 0.02 and 0.04 μg/ml, respectively. The percent CV calculated for intraday and inter day precision was <7.64% and <4.92%, respectively. The intra assay and interassay bias calculated for the determination of accuracy ranged between −4.07% and 5.28% and between −3.76% and 2.97%, respectively.
3.2 | PKs of danofloxacin
The semi- logarithmic plasma concentration–time curves and PK parameters of danofloxacin following IV, IM, SC, and PO administrations at a dose of 10 mg/kg in the chukar partridges are presented in Figure 1 and Table 1, respectively. The mean
t1/2ʎz ranged between 8.18 and 12.08 hr, which differed sta-tistically among administration routes (p < 0.05). The mean
F I G U R E 1 Semi- logarithmic plasma concentration–time curves of danofloxacin following intravenous (IV), intramuscular (IM), subcutaneous (SC), and oral (PO) administrations at a dose of 10 mg/kg in chukar partridge (n = 8)
Cmax of danofloxacin following IM, SC, and PO administrations
was 8.05, 9.58, and 3.39 μg/ml at 0.5, 1, and 4 hr, respectively. The mean MRT0–∞ significantly differed as follows: SC > IM-
PO > IV (p < 0.05). The mean AUC0–∞ increased significantly in the order of SC > IV > IM > PO (p < 0.05). Following IM, SC, and PO administrations, the mean bioavailability was 86.33%, 134.40%, and 47.62%, respectively. The mean ClT and Vdss
fol-lowing IV administration were 0.13 L hr−1 kg−1 and 0.96 L/kg,
respectively.
3.3 | PK/PD data of danofloxacin
The integration of in vivo PK and MIC values reported for dano-floxacin is presented in Table 2. The AUC0–24/MIC ratio of >125 hr was obtained following IV and SC administration for three bacteria species, following IM administration for E. coli and P. multocida and following PO administration for P. multocida. Danofloxacin exhibited a Cmax/MIC ratio of > 10 following IM and SC administration for the three bacteria species and following PO administration for E. coli and
P. multocida.
4 | DISCUSSION
No local or systemic adverse effects were observed following the 10 mg/kg IV, IM, SC, and PO administrations of danofloxacin on the chukar partridges. Following administration via the different routes at 5–10 mg/kg dose, danofloxacin had no adverse drug ef-fect on chickens (Knoll, Glünder, & Kietzmann, 1999), ducks (Goudah & Mouneir, 2009), pheasants, guinea fowls, and Japanese quails (Dimitrova et al., 2014).
The mean t1/2ʎz, ClT, and Vdss following IV administration of dano-floxacin in the chukar partridges were 8.18 hr, 0.13 L hr−1 kg−1, and
0.96 L/kg, respectively. The mean t1/2ʎz, ClT, and Vdss of danofloxa-cin ranged between 3.31 and 6.81 hr, 0.45 and 1.61 L hr−1 kg−1, and
4.40 and 8.57 L/kg in chickens (Knoll et al., 1999), ducks (Goudah & Mouneir, 2009), Japanese quail, pheasants, and guinea fowl (Dimitrova et al., 2014), respectively. These findings indicate the slow elimination and limited distribution following IV administration of danofloxacin in chukar partridges according to poultry species mentioned above. However, the t1/2ʎz of danofloxacin in chukar
par-tridges was similar to that in turkeys (8.64 hr, Haritova et al., 2006).
Parameter IV IM SC PO t1/2ʎz (hr) HM 8.18 ± 0.22c 10.16 ± 0.82b 12.08 ± 0.59a 9.44 ± 1.39b AUC0–24 (hr*μg/ml) 70.18 ± 2.08b 56.59 ± 5.24c 82.19 ± 4.42a 30.96 ± 2.31d AUC0–48 (hr*μg/ml) 75.09 ± 1.98b 63.87 ± 5.49c 97.05 ± 4.81a 35.27 ± 2.80d AUC0–∞ (hr*μg/ml) 76.14 ± 1.95b 65.73 ± 5.29c 102.33 ± 4.72a 36.26 ± 3.15d MRT0–∞ (hr) HM 7.29 ± 0.26c 11.49 ± 0.61b 14.42 ± 0.86a 12.36 ± 1.32b MAT (hr) - 4.22 ± 0.57b 7.17 ± 0.89a 5.19 ± 1.51b ClT (L hr−1 kg−1) 0.13 ± 0.00 - - - Vdss (L/kg) 0.96 ± 0.06 - - - Tmax (hr) (median) - 0.5c 1b 4a Cmax (μg/ml) - 8.05 ± 0.91b 9.58 ± 0.41a 3.39 ± 0.28c F % - 86.33 ± 6.62b 134.40 ± 5.18a 47.62 ± 3.93c
Notes. AUC: area under the plasma concentration–time curve; ClT: total clearance; Cmax: peak plasma
concentration; F: absolute bioavailability; HM: harmonic means; MAT: mean absorption time; MRT:
mean residence time; t1/2ʎz: elimination half- life; Tmax: time to reach the maximum concentration;
Vdss: volume of distribution at steady- state.
a,b,c,d: Varied characters in the same row are statistically different (p < 0.05).
TA B L E 1 Plasma pharmacokinetic parameters of danofloxacin following intravenous (IV), intramuscular (IM), subcutaneous (SC), and oral (PO) administrations at a dose of 10 mg/kg in chukar partridges (n = 8) TA B L E 2 PK/PD integration following intravenous (IV), intramuscular (IM), subcutaneous (SC), and oral (PO) administrations at a dose of 10 mg/kg in chukar partridges Route Mycoplasma gallisepticum
(MIC ≤ 0.5 μg/ml) Escherichia coli (MIC ≤ 0.25 μg/ml) Pasteurella multocida (MIC ≤ 0.05 μg/ml)
AUC0–24/MIC Cmax/MIC AUC0–24/MIC Cmax/MIC AUC0–24/MIC Cmax/MIC
IV 140.36 - 280.72 - 1403.60 -
IM 113.18 16.10 226.36 32.20 1131.80 161.00
SC 164.38 19.16 328.76 38.32 1643.80 191.6
PO 61.92 6.78 123.84 13.56 619.20 67.8
The distribution volume of danofloxacin is large due to its lipophilic structure and low binding to plasma proteins (Goudah & Mouneir, 2009). The binding ratio of danofloxacin to plasma proteins varies among species, being 17% and 27% in ducks (Goudah & Mouneir, 2009) and turkeys (Haritova et al., 2006), respectively. In the pres-ent study, the binding ratio of danofloxacin to plasma proteins was not determined. The smaller Vdss in chukar partridges compared with that in other poultry species might be related to the differ-ent binding ratio of danofloxacin to plasma proteins. The metabolic pathway of danofloxacin is unclear and also varies among species. It has been reported that danofloxacin is generally metabolized to N- desmethyldanofloxacin, N- oxide, and glucuronide- conjugate me-tabolites (Anonymous, 2018). Although N- desmethyldanofloxacin is detected in chickens (Anonymous, 2018), it has not been detected in Japanese quails (Haritova, Dimitrova, Dinev, Moutafchieva, & Lashev, 2013). Poultry species mainly excrete danofloxacin via the kidneys and liver (Yang et al., 2015). There are various differences among poultry species in nephron numbers and in glomerular and tubular blood flow (Frazier, Jones, & Orosz, 1995). The lower CIT in chukar partridges compared with other poultry species might be due to differences in the metabolic pathway and/or kidney excretion of danofloxacin.
Following IV, IM, SC, and PO administration of danofloxacin, there were significant differences in t1/2ʎz, in the order of SC > IM- PO > IV. The longer t1/2ʎz following SC, IM, and PO administration compared with that following IV administration might be due to the biphasic absorption of danofloxacin and flip- flop kinetics. However, the MAT values obtained in this study do not support the “flip- flop” phenomenon. Danofloxacin has exhibited the biphasic absorption following PO administration in turkeys (Haritova et al., 2006).
The AUC0–∞ of danofloxacin in chukar partridges dif-fered significantly among administration routes in the order of SC > IV > IM > PO. The difference in AUC among administration routes might be associated with changes in the plasma concentra-tion–time curve, which, in turn, results from the slow absorption caused by variable biphasic absorption according to administra-tion routes. The mean bioavailability of danofloxacin follow-ing IM, SC, and PO administration was 86.33%, 134.40%, and 47.62%, respectively. The bioavailability following extravascular administration is determined in comparison with that for IV ad-ministration and is generally ≤100% (Toutain & Bousquet- Mélou, 2004). However, the bioavailability of 134.40% following SC ad-ministration in chukar partridges might be due to the distinct bi-phasic absorption process of danofloxacin in this administration route. Bioavailability following PO administration in chukar par-tridges was 47.62%, which was much lower than that previously reported in turkeys (78.37%, Haritova et al., 2006) and Japanese quail, pheasants, and guinea fowl (79.46%–83.50%, Dimitrova et al., 2014). It has been reported that differences in the diges-tive system affect oral drug absorption in pheasants and chickens (Anadon, 1999). Danofloxacin is a substrate of efflux transporters, such as P- glycoprotein, multidrug resistance- associated protein 2,
and breast cancer resistance protein (Schrickx & Fink- Gremmels, 2007). Efflux transporters contribute to the function of the in-testinal barrier (Haritova, Schrickx, Lashev, & Fink- Gremmels, 2008). Species differences in the expression levels of efflux trans-porters have previously been determined (Zamek- Gliszczynski, Hoffmaster, Nezasa, Tallman, & Brouwer, 2006). In the present study, the low PO bioavailability of danofloxacin in chukar par-tridges compared with that in other poultry species may be asso-ciated with limited absorption of danofloxacin due to a difference in gastrointestinal system organs and in the expression levels of efflux transporters.
The antibacterial activity of danofloxacin is dependent on its concentration and the MIC established for susceptible micro- organisms (Zhang et al., 2017). MIC data of danofloxacin against susceptible micro- organisms isolated from chukar partridges have not been reported to date. However, the reported MIC values for
M. gallisepticum, E. coli, and P. multocida isolated from different
poultry species were reported to be 0.15–0.5 (Cooper et al., 1993; Zhang et al., 2017), 0.125–0.25 (Geornaras et al., 2001; Haritova et al., 2006) and 0.05 μg/ml (Zeng et al., 2011), respectively. For concentration- dependent antibacterial agents, a Cmax/MIC of >10 and AUC0–24/MIC of >125 are suggested to give maximum clinical and bacteriology efficacy and to prevent the emergence of resis-tant organisms (McKellar, Sanchez Bruni, & Jones, 2004; Toutain & Bousquet- Mélou, 2004; Toutain, del Castillo, & Bousquet- Mélou, 2002; Wright, Brown, Peterson, & Rotschafer, 2000). In the present study, a Cmax/MIC ratio of >10 and an AUC0–24/MIC ratio of >125 were obtained for M. gallisepticum, E. coli, and P. multocida following SC administration, E. coli and P. multocida following IM administra-tion, and P. multocida following PO administration from bacteria mentioned the MIC value above. These ratios were higher than those required for efficient treatment. However, it is not possible to predict the actual efficacy of dosage in chukar partridges with-out clinical investigation involving animals with natural disease or disease models.
In conclusion, the favorable PKs including a long half- life and a high bioavailability, following especially SC and IM administration and the absence of adverse drug effects, indicate that danofloxacin may be a potentially useful antibiotic in chukar partridges. On the other hand, PO administration via drinking water or feed in poultry is usually the most suitable route. Therefore, the low absorption of danofloxacin following PO administration in chukar partridges can be improved by the development of its oral formulations and by its administration at a dose of >10 mg/kg. Danofloxacin at a dose of 10 mg/kg in the treatment of infections caused by M.
gallisepti-cum (MIC ≤ 0.5 μg/ml), E. coli (MIC ≤ 0.25 μg/ml), and P. multocida
(MIC ≤ 0.05 μg/ml) in chukar partridges provided different ratios of Cmax/MIC and AUC0–24/MIC according to administration route. Therefore, the administration route of danofloxacin is important in the treatment of infections caused by susceptible bacteria. Further investigation is required for determining the in vitro and in vivo an-tibacterial efficiencies and multiple dosage regimes of danofloxacin against pathogens isolated in chukar partridges.
ACKNOWLEDGMENTS
This study was presented in abstract form as oral presentation to the 4th International Congress on Veterinary and Animal Sciences “(ICVAS),” Nevsehir, Turkey, 12–15 July 2018.
CONFLIC T OF INTEREST
The authors declare no conflict of interests. AUTHORS’ CONTRIBUTION
OC and KU contributed to conception, design, analysis, and acquisi-tion, drafted the manuscript, critically revised the manuscript, gave final approval, and agreed to be accountable for all aspects of work ensuring integrity and accuracy. DDC, OA, HEF, and FA contributed to analysis and agreed to be accountable for all aspects of work en-suring integrity and accuracy.
ORCID
Orhan Corum http://orcid.org/0000-0003-3168-2510 Duygu Durna Corum http://orcid.org/0000-0003-1567-991X Feray Altan http://orcid.org/0000-0002-9017-763X Kamil Uney http://orcid.org/0000-0002-8674-4873
REFERENCES
Anadon, A.. (1999). Bioavailability in birds: physiological basis and clinical consequences. In: Materials of the Training Workshop on Pharmacokinetics, Toulouse, France. 6–10th September 1999. Anonymous. (2018). . http://www.fao.org/docrep/W8338E/w8338e07.
htm
Charleston, B., Gate, J. J., Aitken, I. A., Stephan, B., & Froyman, R. (1998). Comparison of the efficacies of three fluoroquinolone antimicrobial agents, given as continuous or pulsed- water medication, against Escherichia coli infection in chickens. Antimicrobial Agents and
Chemotherapy, 42, 83–87. https://doi.org/10.1128/AAC.42.1.83
Cooper, A. C., Fuller, J. R., Fuller, M. K., Whittlestone, P., & Wise, D. R. (1993). In vitro activity of danofloxacin, tylosin and oxytetracycline against mycoplasmas of veterinary importance. Research in Veterinary Science,
54, 329–334. https://doi.org/10.1016/0034-5288(93)90130-8
CVMP (2002). Danofloxacin (extension to all food producing species) summary report (6). European Agency for the Evaluation of Medicinal Products, EMA/MRL/818/02-FINAL.
Dimitrova, D. J., Haritova, A. M., Dinev, T. D., Moutafchieva, R. G., & Lashev, L. D. (2014). Comparative pharmacokinetics of danofloxacin in common pheasants, guinea fowls and Japanese quails after intra-venous and oral administration. British Poultry Science, 55, 120–125. https://doi.org/10.1080/00071668.2013.871502
Frazier, D. L., Jones, M. P., & Orosz, S. E. (1995). Pharmacokinetic consid-erations of the renal system in birds: Part i. anatomic and physiologic principles of allometric scaling. Journal of Avian Medicine and Surgery,
9, 92–103.
Geornaras, I., Hastings, J. W., & von Holy, A. (2001). Genotypic analysis of
Escherichia coli strains from poultry carcasses and their
susceptibili-ties to antimicrobial agents. Applied and Environmental Microbiology,
67, 1940–1944. https://doi.org/10.1128/AEM.67.4.1940-1944.2001
Goudah, A., & Mouneir, S. M. (2009). Disposition kinetics and tissue res-idues of danofloxacin in Muscovy ducks. British Poultry Science, 50, 613–619. https://doi.org/10.1080/00071660903147416
Haritova, A., Dimitrova, D., Dinev, T., Moutafchieva, R., & Lashev, L. (2013). Comparative pharmacokinetics of enrofloxacin, danofloxa-cin, and marbofloxacin after intravenous and oral administration in Japanese quail (Coturnix coturnix japonica). Journal of Avian Medicine
and Surgery, 27, 23–31. https://doi.org/10.1647/2011-032
Haritova, A. M., Rusenova, N. V., Parvanov, P. R., Lashev, L. D., & Fink-Gremmels, J. (2006). Pharmacokinetic- pharmacodynamic modelling of danofloxacin in turkeys. Veterinary Research Communications, 30, 775–789. https://doi.org/10.1007/s11259-006-3400-7
Haritova, A. M., Schrickx, J., Lashev, L. D., & Fink-Gremmels, J. (2008). Expression of MDR1, MRP2 and BCRP mRNA in tissues of turkeys.
Journal of Veterinary Pharmacology and Therapeutics, 31, 378–385.
https://doi.org/10.1111/j.1365-2885.2008.00968.x
Jordan, F. T., Horrocks, B. K., Jones, S. K., Cooper, A. C., & Giles, C. J. (1993). A comparison of the efficacy of danofloxacin and tylosin in the control of Mycoplasma gallisepticum infection in broiler chicks.
Journal of Veterinary Pharmacology and Therapeutics, 16, 79–86.
https://doi.org/10.1111/j.1365-2885.1993.tb00292.x
Knoll, U., Glünder, G., & Kietzmann, M. (1999). Comparative study of the plasma pharmacokinetics and tissue concentrations of danofloxacin and enrofloxacin in broiler chickens. Journal of
Veterinary Pharmacology and Therapeutics, 22, 239–246. https://doi.
org/10.1046/j.1365-2885.1999.00217.x
McKellar, Q. A., Sanchez Bruni, S. F., & Jones, D. G. (2004). Pharmacokinetic/ pharmacodynamic relationships of anti- microbial drugs used in vet-erinary medicine. Journal of Vetvet-erinary Pharmacology and Therapeutics,
27, 503–514. https://doi.org/10.1111/j.1365-2885.2004.00603.x
Nakamura, S. (1995). Veterinary use of new quinolones in Japan. Drugs, 49, 152–158. https://doi.org/10.2165/00003495-199500492-00025 Nelson, J. M., Chiller, T. M., Powers, J. H., & Angulo, F. J. (2007).
Fluoroquinolone- resistant Campylobacter species and the with-drawal of fluoroquinolones from use in poultry: A public health success story. Clinical Infectious Diseases, 44, 977–980. https://doi. org/10.1086/512369
Potter, T., Illambas, J., Pelligand, L., Rycroft, A., & Lees, P. (2013). Pharmacokinetic and pharmacodynamic integration and modelling of marbofloxacin in calves for Mannheimia haemolytica and Pasteurella
multocida. Veterinary Journal, 195, 53–58. https://doi.org/10.1016/j.
tvjl.2012.08.027
Real, R., Egido, E., Perez, M., Gonzalez-Lobato, L., Barrera, B., Prieto, J. G., & Merino, G. (2011). Involvement of breast cancer resistance protein (BCRP⁄ABCG2) in the secretion of danofloxacin into milk: Interaction with ivermectin. Journal of Veterinary Pharmacology and Therapeutics,
34, 313–321. https://doi.org/10.1111/j.1365-2885.2010.01241.x
Schrickx, J. A., & Fink-Gremmels, J. (2007). Danofloxacin- mesylate is a substrate for ATP- dependent efflux transporters. British Journal of
Pharmacology, 150, 463–469.
Summa, N. M., & Guzman, D. S. (2017). Evidence- based advances in avian medicine. The Veterinary Clinics of North America Exotic Animal
Practice, 20, 817–837. https://doi.org/10.1016/j.cvex.2017.04.002
Toutain, P. L., & Bousquet-Mélou, A. (2004). Bioavailability and its as-sessment. Journal of Veterinary Pharmacology and Therapeutics, 27, 455–466. https://doi.org/10.1111/j.1365-2885.2004.00604.x Toutain, P. L., del Castillo, J. R., & Bousquet-Mélou, A. (2002). The
pharmacokinetic- pharmacodynamic approach to a rational dosage regimen for antibiotics. Research in Veterinary Science, 73, 105–114. https://doi.org/10.1016/S0034-5288(02)00039-5
Walker, R. D. (2000). The use of fluoroquinolones for companion ani-mal antimicrobial therapy. Australian Veterinary Journal, 78, 84–90. https://doi.org/10.1111/j.1751-0813.2000.tb10528.x
Wright, D. H., Brown, G. H., Peterson, M. L., & Rotschafer, J. C. (2000). Application of fluoroquinolone pharmacodynamics. The Journal of
Antimicrobial Chemotherapy, 46, 669–683. https://doi.org/10.1093/
jac/46.5.669
Yang, F., Sun, N., Liu, Y. M., & Zeng, Z. L. (2015). Estimating danofloxacin withdrawal time in broiler chickens based on physiologically based pharmacokinetics modeling. Journal of Veterinary Pharmacology and
Therapeutics, 38, 174–182. https://doi.org/10.1111/jvp.12162
Zamek-Gliszczynski, M. J., Hoffmaster, K. A., Nezasa, K., Tallman, M. N., & Brouwer, K. L. R. (2006). Integration of hepatic drug transporters and phase II metabolizing enzymes: Mechanisms of hepatic excretion of sulfate, glucuronide, and glutathione metabolites. European Journal
of Pharmaceutical Sciences, 27, 447–486. https://doi.org/10.1016/j.
ejps.2005.12.007
Zeng, Z., Deng, G., Shen, X., Rizwan-Ul-Haq, M., Zeng, D., & Ding, H. (2011). Plasma and tissue pharmacokinetics of danofloxacin in healthy and in experimentally infected chickens with Pasteurella multocida. Journal of Veterinary Pharmacology and Therapeutics, 34, 101–114. https://doi.org/10.1111/j.1365-2885.2010.01223.x
Zhang, N., Wu, Y., Huang, Z., Yao, L., Zhang, L., Cai, Q., & Ding, H. (2017). The PK–PD relationship and resistance development of dano-floxacin against Mycoplasma gallisepticum in an in vivo infection model. Frontiers in Microbiology, 8, 926. https://doi.org/10.3389/ fmicb.2017.00926
How to cite this article: Corum O, Durna Corum D, Atik O, Eser Faki H, Altan F, Uney K. Pharmacokinetics and bioavailability of danofloxacin in chukar partridge (Alectoris
chukar) following intravenous, intramuscular, subcutaneous,
and oral administrations. J vet Pharmacol Therap. 2019;42:207–213. https://doi.org/10.1111/jvp.12737
