Pharmacokinetics of pradofloxacin and doxycycline in serum, saliva, and tear fluid of cats after oral administration

Hartmann, Anja; Krebber, Ralph; Daube, G. W.; Hartmann, Katrin

doi:10.1111/j.1365-2885.2007.00932.x

Cited by 33 publications

(38 citation statements)

References 51 publications

(54 reference statements)

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“…In cats, doxycycline is 99% protein bound and was not detectable in tears following oral administration of a single dose of 5 mg/kg (2.3 mg/lb). 18,19 By contrast, plasma protein binding of doxycycline after oral administration has been reported to be less in horses (82%) and was associated with a relatively high Cmax in tears (9,830 ng/mL) following administration of 20 mg of doxycycline/kg once daily. 3 The Cmax for doxycycline in northern elephant seal tears in the present study (250 ng/mL) was less than has been reported in horses (9,830 ng/mL) 3 but higher than in cats.…”

Section: Discussionmentioning

confidence: 99%

“…The concentration of antimicrobial compounds in tears is influenced by a number of intrinsic properties of the drugs (protein binding, lipophilicity, molecular weight, and degree of ionization), characteristics of the tears themselves (pH and flow rate), and transport mechanisms, such as diffusion and active transport. 18 Of these, plasma protein binding exerts a particularly important influence on a compound' s distribution in interstitial fluids with more highly proteinbound compounds distributing less well into low-protein fluids such as tears than do less highly protein-bound compounds. The degree to which doxycycline is protein bound in northern elephant seals was not measured in the present study; however, data from other studies permit some hypotheses to be made.…”

Section: Discussionmentioning

confidence: 99%

“…3 The Cmax for doxycycline in northern elephant seal tears in the present study (250 ng/mL) was less than has been reported in horses (9,830 ng/mL) 3 but higher than in cats. 18 These prior studies of horses and cats served as the basis for the doses selected for the present study. As-suming other factors are equal, findings from the present study in conjunction with findings from these previous studies suggest that doxycycline binds to plasma proteins in northern elephant seals at a rate intermediate between the rates for cats and horses.…”

Section: Discussionmentioning

confidence: 99%

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Population pharmacokinetics of doxycycline in the tears and plasma of northern elephant seals (Mirounga angustirostris) following oral drug administration

Freeman¹,

Thomasy²,

Stanley³

et al. 2013

javma

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Objective-To assess tear and plasma concentrations of doxycycline following oral administration to northern elephant seals (Mirounga angustirostris). Design-Pharmacokinetic study. Animals-18 juvenile northern elephant seals without signs of ocular disease. Procedures-Study seals were receiving no medications other than a multivitamin and were free from signs of ocular disease as assessed by an ophthalmic examination. Doxycycline (10 or 20 mg/kg [4.5 or 9.1 mg/lb]) was administered orally every 24 hours for 4 days. Tear and plasma samples were collected at fixed time points, and doxycycline concentration was assessed by means of liquid chromatography-tandem mass spectrometry. Concentration-time data were calculated via noncompartmental analysis. Results-Following administration of doxycycline (10 mg/kg/d, PO), maximum plasma doxycycline concentration was 2.2 µg/mL at 6.1 hours on day 1 and was 1.5 µg/mL at 4.0 hours on day 4. Administration of doxycycline (20 mg/kg/d, PO) produced a maximum plasma doxycycline concentration of 2.4 µg/mL at 2.3 hours on day 1 and 1.9 µg/mL at 5.8 hours on day 4. Doxycycline elimination half-life on day 4 in animals receiving doxycycline at a dosage of 10 or 20 mg/kg/d was 6.7 or 5.6 hours, respectively. Mean plasma-to-tear doxycycline concentration ratios over all days were not significantly different between the low-dose (9.85) and high-dose (9.83) groups. For both groups, doxycycline was detectable in tears for at least 6 days following cessation of dosing. Conclusions and Clinical Relevance-Oral administration of doxycycline at the doses tested in the present study resulted in concentrations in the plasma and tears of northern elephant seals likely to be clinically effective for treatment of selected cases of systemic infectious disease, bacterial ulcerative keratitis, and ocular surface inflammation. This route of administration should be considered for treatment of corneal disease in northern elephant seals and possibly other related pinniped species. (J Am Vet

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Population pharmacokinetics of doxycycline in the tears and plasma of northern elephant seals (Mirounga angustirostris) following oral drug administration

Freeman¹,

Thomasy²,

Stanley³

et al. 2013

javma

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“…Hartmann et al . () proposed that P‐gp/MDR1, which is expressed in the respiratory tract, may be responsible for secretion of pradofloxacin into saliva and tear fluid. However, not all fluoroquinolones are substrates for this transporter so that its role in relation to pradofloxacin transport, if any, remains to be elucidated.…”

Section: Pharmacokineticsmentioning

confidence: 99%

Pharmacokinetics, pharmacodynamics and therapeutics of pradofloxacin in the dog and cat

Lees

2013

Vet Pharm & Therapeutics

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Pradofloxacin is a third-generation fluoroquinolone, licensed in the EU for use in a range of indications in the dog and cat and authorized more recently in the USA for one therapeutic indication (skin infections) in the cat. This review summarizes and appraises current knowledge on the physico-chemical, pharmacological [pharmacokinetics (PK) and pharmacodynamics (PD)], safety and therapeutic properties of pradofloxacin in the target species. Pradofloxacin contains two centres of asymmetry and is the pure SS enantiomer. After oral dosing of tablets (dog) or tablets and oral suspension (cat), maximum plasma concentrations (Cmax ) are achieved in less than 3.0 h, and terminal half-life is of the order of 5-10 h. Accumulation is slight or absent with once daily oral dosing. Free drug concentrations in plasma are in the range of 63-71% of total concentration. As for other fluoroquinolones, antibacterial activity is attributable to inhibition of bacterial replication at two sites, subunit A of topoisomerase II and topoisomerase IV. The antimicrobial spectrum includes gram-negative and gram-positive organisms, anaerobes, Mycoplasma spp. and some intracellular organisms (Rickettsia spp. and Mycobacterium spp.). The killing action is of the concentration-dependent type. Pradofloxacin has high potency (low MIC values) in comparison with first- and second-generation fluoroquinolones. Integration of in vivo PK and in vitro PD data provides values of Cmax /MIC and area under plasma concentration-time curve (AUC24 h )/MIC ratios predictive of good clinical efficacy against sensitive organisms, when administered at recommended dose rates. Clinical trial evaluation of pradofloxacin, in comparison with other authorized antimicrobial drugs, has demonstrated either noninferiority or superiority of pradofloxacin. Data indicating clinical and, in some instances, bacteriological cure have been reported: (i) in cats, for wound infections, abscesses, upper respiratory tract infections, conjunctivitis, feline infectious anaemia and lower urinary tract infections and (ii) in dogs, for wound infections, superficial and deep pyoderma, acute urinary tract infections and adjunctive treatment of infections of gingival and periodontal tissues. At clinical dose rates pradofloxacin was well tolerated in preclinical studies and in clinical trials. Among the advantages of pradofloxacin are (i) successful treatment of infections caused by strains resistant to some other fluoroquinolones, as predicted by PK/PD data, but depending on the specific MIC of the target strain and (ii) a reduced propensity for resistance development based on MPC measurements. The preclinical and clinical data on pradofloxacin suggest that this drug should commonly be the fluoroquinolone of choice when a drug of this class is indicated. However, the PK/PD data on pradofloxacin, in comparison with other fluoroquinolones, are not a factor that leads automatically to greater clinical efficacy.

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“…In cats, concentrations of drugs in tears following oral administration vary and range from undetectable (doxycycline) to concentrations that exceed plasma concentrations (pradofloxacin). 28 For the cats of the present study, the penciclovir concentration in tears was approximately 20% of that in plasma. Simply modeling tear drug concentration as a fraction of the plasma drug concentration provided an acceptable fit for the observed data for penciclovir, but provided a poor fit for the BRL42359 data.…”

Section: Discussionmentioning

confidence: 94%

Pharmacokinetic modeling of penciclovir and BRL42359 in the plasma and tears of healthy cats to optimize dosage recommendations for oral administration of famciclovir

Sebbag

Thomasy

Woodward

et al. 2016

ajvr

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TitlePharmacokinetic modeling of penciclovir and brl42359 in the plasma and tears of healthy cats to optimize dosage recommendations for oral administration of famciclovir OBJECTIVESTo determine, following oral administration of famciclovir, pharmacokinetic (PK) parameters for 2 of its metabolites (penciclovir and BRL42359) in plasma and tears of healthy cats so that famciclovir dosage recommendations for the treatment of herpetic disease can be optimized. ANIMALS7 male domestic shorthair cats. PROCEDURESIn a crossover study, each of 3 doses of famciclovir (30, 40, or 90 mg/kg) was administered every 8 or 12 hours for 3 days. Six cats were randomly assigned to each dosage regimen. Plasma and tear samples were obtained at predetermined times after famciclovir administration. Pharmacokinetic parameters were determined for BRL42359 and penciclovir by compartmental and noncompartmental methods. Pharmacokinetic-pharmacodynamic (PK-PD) indices were determined for penciclovir and compared among all dosage regimens. RESULTSCompared with penciclovir concentrations, BRL42359 concentrations were 5-to 11-fold greater in plasma and 4-to 7-fold greater in tears. Pharmacokinetic parameters and PK-PD indices for the 90 mg/kg regimens were superior to those for the 30 and 40 mg/kg regimens, regardless of dosing frequency. Penciclovir concentrations in tears ranged from 18% to 25% of those in plasma. Administration of 30 or 40 mg/kg every 8 hours achieved penciclovir concentrations likely to be therapeutic in plasma but not in tears. Penciclovir concentrations likely to be therapeutic in tears were achieved only with the two 90 mg/kg regimens. CONCLUSIONS AND CLINICAL RELEVANCEIn cats, famciclovir absorption is variable and its metabolism saturable. Conversion of BRL42359 to penciclovir is rate limiting. The recommended dosage of famciclovir is 90 mg/kg every 12 hours for cats infected with feline herpesvirus. (Am J Vet Res 2016;77:833-845)

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Pharmacokinetics of pradofloxacin and doxycycline in serum, saliva, and tear fluid of cats after oral administration

Cited by 33 publications

References 51 publications

Population pharmacokinetics of doxycycline in the tears and plasma of northern elephant seals (Mirounga angustirostris) following oral drug administration

Population pharmacokinetics of doxycycline in the tears and plasma of northern elephant seals (Mirounga angustirostris) following oral drug administration

Pharmacokinetics, pharmacodynamics and therapeutics of pradofloxacin in the dog and cat

Pharmacokinetic modeling of penciclovir and BRL42359 in the plasma and tears of healthy cats to optimize dosage recommendations for oral administration of famciclovir

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