Pharmacokinetics of a peroral single dose of two long-acting formulations and an aqueous formulation of doxycycline hyclate in horses

Zozaya, Heidi; Gutiérrez, Lilia; Bernad, María Josefa Bernad; López, Héctor Sumano

doi:10.1186/1751-0147-55-21

Cited by 18 publications

(24 citation statements)

References 30 publications

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“…Pharmacokinetic analysis of STD-doxy and previous LE-doxy formulations using different loading methodologies has been described by a number of investigators (Blanchard et al, 1975;Saivin and Houin, 1988;Kelly et al, 1992;Sangaré et al, 2001a,b;Selliah and Ravaoarinoro, 2004;Rolain et al, 2005;Agwuh and MacGowan, 2006;Zozaya et al, 2013;Gutierrez et al, 2014). We obtained lower values of AUC, C max , and MRT for STD-doxy when compared with the LE-doxy formulations.…”

Section: Discussionmentioning

confidence: 99%

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A Novel Loading Method for Doxycycline Liposomes for Intracellular Drug Delivery: Characterization of In Vitro and In Vivo Release Kinetics and Efficacy in a J774A.1 Cell Line Model ofMycobacterium smegmatisInfection

et al. 2015

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Doxycycline (doxy) is used in treating intracellular and extracellular infections. Liposomal (LE) antibiotics allow low-frequency dosing and extended efficacy compared with standard (STD) formulations. We developed a novel sulfuric acid-loading method for doxycycline liposomes (LE-doxy). We hypothesized that a single s.c. injection of LE-doxy would be detectable in serum for at least 2 weeks at concentrations equal to or better than STD-doxy and would be bactericidal in an in vitro Mycobacterium smegmatis infection of J774A.1 macrophage cells. Liposomes were encapsulated by sulfuric acid gradient loading, and release kinetics were performed in vitro and in vivo. LE-doxy made using 8.25 mg/ml doxycycline loaded for 24 hours achieved 97.77% capture in 1,2-dipalmitoyl-snglycero-3-phosphocholine (DPPC) and 43.87% in sphingomyelin (sphing). Rats were injected s.c. with 50 mg/kg LE-doxy or 5 mg/kg STD-doxy, and serial blood samples were collected. Pharmacokinetics were analyzed using high-performance liquid chromatography. Liver and injection site skin samples were collected at euthanasia (4 weeks postinjection). Minimal histologic tissue reactions occurred after injection of STD (nonliposomal), DPPC, or sphing-doxy. DPPC-doxy had slightly faster in vitro leakage than sphing liposomes, although both were detectable at 264 hours. The mean residence time for DPPC was the highest (111.78 hours), followed by sphing (56.00 hours) and STD (6.86 hours). DPPC and sphing-doxy were detectable at 0.2 mg/ml in serum at 336 hours postadministration. LE-doxy was not toxic to J774A.1 cells in vitro and produced inhibition of viable Mycobacterium smegmatis at 24 and 48 hours. LE-doxy will require further testing in in vivo infection models.

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Section: Discussionmentioning

confidence: 99%

“…STD-doxy has a pH between 1.8 and 3.3 and is not recommended for i.m. or s.c. use due to the potential for injection site pain, irritation, and tissue necrosis (Zozaya et al, 2013). A nonpainful injection site bulge was reported in dogs receiving a long-acting formulation, although histology was not performed (Gutierrez et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

A Novel Loading Method for Doxycycline Liposomes for Intracellular Drug Delivery: Characterization of In Vitro and In Vivo Release Kinetics and Efficacy in a J774A.1 Cell Line Model ofMycobacterium smegmatisInfection

et al. 2015

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“…The PK/PD parameter of AUC/MIC (area under the curve to MIC ratio) was commonly used as the preferred target to estimate the therapeutic efficacy for tetracycline antibiotics (Embers, Hasenkampf, Embers, & Doyle, 2013;Zozaya, Gutierrez, Bernad, & Sumano, 2013), and an AUC 0-24 hr /MIC of ≥25 hr was utilized for minocycline against Staphylococcus pseudintermedius infections in dogs (Maaland et al, 2014). The MIC data of minocycline against crucian carp bacterial isolates have not been reported until now.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of minocycline in crucian carp (Carassius auratus ) after intravenous and oral administration

Yang

et al. 2018

Aquac Res

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The pharmacokinetic of minocycline was studied after a single intravenous as well as oral dose (5 mg/kg body weight) in crucian carp (Carassius auratus) reared in freshwater at 10°C. Plasma samples were randomly collected from six fish at each sampling time. Plasma concentrations were determined by high-performance liquid chromatography and further subjected to noncompartmental analysis. Initial concentration of minocycline just after intravenous administration was calculated as 7.320 lg/ml, while the other parameters after intravenous injection were determined as flows: apparent elimination rate constant (k z ) of 0.064 per hr, apparent elimination half-life (t 1=2kz ) of 10.82 hr, total body clearance (Cl) of 142.72 ml/hr/kg, volume of distribution (Vz) of 2,227.38 ml/kg and volume of distribution at steadystate (Vss) of 1,937.08 ml/kg. While after oral administration, the k z , t 1=2kz , mean absorption time (MAT), absorption half-life (t 1/2ka ) and bioavailability were determined as 0.059 per hr, 11.74, 5.55, 3.84 hr, and 81.98%, respectively, and the peak concentration was observed as 1.474 AE 0.362 lg/ml at 8 hr. It was shown that minocycline was slowly but relatively completely absorbed, extensively distributed, and slowly eliminated in crucian carp. Based on the ratios of AUC 0-24 hr /MIC90, a minocycline dosage of 5 mg/kg body weight administered intravenously or orally would be only effective to successfully treat crucian carp infected by bacterium with MIC values ≤0.25 lg/ml. K E Y W O R D S bioavailability, crucian carp, minocycline, oral administration, pharmacokinetic wileyonlinelibrary.com/journal/are Aquaculture Research. 2018;49:2782-2787.

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“…Compared with other tetracyclines, doxycycline has better pharmacokinetics characteristics in mammals, including superior absorption rate following oral administration and the increased distribution to various body tissues (Aronson, ; Riond & Riviere, ). Pharmacokinetics of doxycycline in different species have been studied, such as in dogs (Gutierrez et al ., ), cats (Hartmann et al ., ), chicken (Yang et al ., ), pigs (Yang et al ., ), horses (Zozaya et al ., ), sheep (Castro Robles et al ., ), goats (Vargas et al ., ), and calves (Vargas‐Estrada et al ., ). However, pharmacokinetics profiles of doxycycline in fish species, especially its oral bioavailability, are very limited.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of doxycycline in tilapia (Oreochromis aureus × Oreochromis niloticus) after intravenous and oral administration

Yang

et al. 2014

Vet Pharm & Therapeutics

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The pharmacokinetics of doxycycline was studied in plasma after a single dose (20 mg/kg) of intravenous or oral administration to tilapia (Oreochromis aureus × Oreochromis niloticus) reared in fresh water at 24 °C. Plasma samples were collected from six fish per sampling point. Doxycycline concentrations were determined by high-performance liquid chromatography with a 0.005 μg/mL limit of detection, then were subjected to noncompartmental analysis. Following oral administration, the double-peak phenomenon was observed, and the first (Cmax1 ) and second (Cmax2) peaks were 1.99 ± 0.43 μg/mL at 2.0 h and 2.27 ± 0.38 μg/mL at 24.0 h, respectively. After the intravenous injection, a Cmax2 (12.12 ± 1.97 μg/mL) was also observed, and initial concentration of 45.76 μg/mL, apparent elimination rate constant (λz) of 0.018 per h, apparent elimination half-life (t1/2λz) of 39.0 h, systemic total body clearance (Cl) of 41.28 mL/h/kg, volume of distribution (Vz) of 2323.21 mL/kg, and volume of distribution at steady-state (Vss) of 1356.69 mL/kg were determined, respectively. While after oral administration, the λz, t1/2λz, and bioavailability of doxycycline were 0.009 per h, 77.2 h, and 23.41%, respectively. It was shown that doxycycline was relatively slowly and incompletely absorbed, extensively distributed, and slowly eliminated in tilapia, in addition, doxycycline might undergo enterohepatic recycling in tilapia.

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Pharmacokinetics of a peroral single dose of two long-acting formulations and an aqueous formulation of doxycycline hyclate in horses

Cited by 18 publications

References 30 publications

A Novel Loading Method for Doxycycline Liposomes for Intracellular Drug Delivery: Characterization of In Vitro and In Vivo Release Kinetics and Efficacy in a J774A.1 Cell Line Model ofMycobacterium smegmatisInfection

A Novel Loading Method for Doxycycline Liposomes for Intracellular Drug Delivery: Characterization of In Vitro and In Vivo Release Kinetics and Efficacy in a J774A.1 Cell Line Model ofMycobacterium smegmatisInfection

Pharmacokinetics of minocycline in crucian carp (Carassius auratus ) after intravenous and oral administration

Pharmacokinetics of doxycycline in tilapia (Oreochromis aureus × Oreochromis niloticus) after intravenous and oral administration

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