• Journal of Veterinary Science
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• v.21 no.6
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• pp.87.1-87.11
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• 2020

Background: A new, extended long-acting tilmicosin (TLAe) preparation was tested against intramammary ceftiofur (CEF) using a non-inferiority trial model during dry-cow therapy (DCT) in a farm with high bovine population density and deficient hygiene application. Objectives: To evaluate the possibility that TLAe administered parenterally can achieve non-inferiority status compared to CEF administered intramammary for DCT. Methods: Cows were randomly assigned to TLAe (20 mg/kg subcutaneous; n = 53) or CEF (CEF-HCl, 125 mg/quarter; n = 38 cows) treatment groups. California mastitis testing, colony-forming unit assessment (CFU/mL), and number of cases positive for Staphylococcus aureus were quantified before DCT and 7 d after calving. A complete cure was defined as no bacteria isolated; partial cure when CFU/mL ranged from 150 to 700, and cure-failure when CFU/mL was above 700. Results: TLAe and CEF had overall cure rates of 57% and 53% (p > 0.05) and S. aureus cure rates of 77.7% and 25%, respectively (p < 0.05). The pathogens detected at DCT and 7 days after calving were S. aureus (62.71% and 35.55%), Staphylococcus spp. (22.03% and 35.55%), Streptococcus uberis (10.16% and 13.33%), and Escherichia coli (5.08% and 15.55%). Non-inferiority and binary logistic regression analyses revealed a lack of difference in overall efficacies of TLAe and CEF. Apart from S. aureus, S. uberis was the predominant pathogen found in both groups. Conclusions: This study is the first successful report of parenteral DCT showing comparable efficacy as CEF, the gold-standard. The extended long-term pharmacokinetic activity of TLAe explains these results.

• Translational and Clinical Pharmacology
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• v.26 no.4
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• pp.160-165
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• 2018

Indobufen ($Ibustrin^{(R)}$), a reversible inhibitor of platelet aggregation, exists in two enantiomeric forms in 1:1 ratio. Here, we characterized the anti-platelet effect of S- and R-indobufen using response surface modeling using $NONMEM^{(R)}$ and predicted the therapeutic doses exerting the maximal efficacy of each enantioselective S- and R-indobufen formulation. S- and R-indobufen were added individually or together to 24 plasma samples from drug-naïve healthy subjects, generating 892 samples containing randomly selected concentrations of the drugs of 0-128 mg/L. Collagen-induced platelet aggregation in platelet-rich plasma was determined using a Chrono-log Lumi-Aggregometer. Inhibitory sigmoid $I_{max}$ model adequately described the anti-platelet effect. The S-form was more potent, whereas the R-form showed less inter-individual variation. No significant interaction was observed between the two enantiomers. The anti-platelet effect of multiple treatments with 200 mg indobufen twice daily doses was predicted in the simulation study, and the effect of S- or R-indobufen alone at various doses was predicted to define optimal dosing regimen for each enantiomer. Simulation study predicted that 200 mg twice daily administration of S-indobufen alone will produce more treatment effect than S-and R-mixture formulation. S-indobufen produced treatment effect at lower concentration than R-indobufen. However, inter-individual variation of the pharmacodynamic response was smaller in R-indobufen. The present study suggests the optimal doses of R-and S-enantioselective indobufen formulations in terms of treatment efficacy for patients with thromboembolic problems. The proposed methodology in this study can be applied to the develop novel enantio-selective drugs more efficiently.

• Korean Journal of Clinical Pharmacy
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• v.8 no.1
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• pp.13-18
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• 1998

The purpose of this study was to determine pharmacokinetic parameters of vancomycin using the compartment model dependent and compartment model independent analysis in 6 Korean normal volunteers and 8 ovarian cancer patients. Vancomycin was administered 1.0 g bolus by IV infusion over 60 minutes. The elimination rate constant ($\beta$), volume of distribution (Vd), total body clearance (CLt), and area under the plasma level-time curve (AUC) of vancomycin in normal volunteers using the compartment model dependent analysis were $0.150\pm0.030\;hr^{-1},\;32.9\pm2.81\;L/kg,\;5.36\pm0.63\;L/hr,\;and\;186.5\pm20.5\;{\mu}g/ml{\cdot}hr$, respectively. The $\beta$, Vd, CLt, and AUC of vancomycin in ovarian cancer patients using the compartment model dependent analysis were $0.109\;0.008\;hr^{-1},\;41.5\pm3.01\;L/kg,\;4.58\pm0.57\;L/hr\;and\;218.3\pm22.9\;{\mu}g/ml{\cdot}hr$, respectively. There were significant differences (p<0.05,\;p<0.01) in $\beta$, Vd, CLt, and AUC between normal volunteers and ovarian cancer patients. The elimination rate constant (Kel), CLt, and AUC of vancomycin in normal volunteers using the compartment model independent analysis were $0.152\pm0.022\;hr^{-1},\;5.77\pm0.75\;L/hr,\;and\;173.2\pm22.5;{\mu}g/ml{\cdot}hr$, respectively. The Kel, CLt, and AUC of vancomycin in ovarian cancer patients using the compartment model independent analysis were $0.126\pm0.012\;hr^{-1},\;4.96\pm0.55\;L/hr,\;and\;201.7\pm25.6;{\mu}g/ml{\cdot}hr$, respectively. There were significant differences (p<0.05, p<0.01) in Kel, CLt, and AUC between normal volunteers and ovarian cancer patients. And also, there was significant difference (p<0.05) in Kel of vancomycin in ovarian cancer patients between the compartment model dependent and independen analysis. It is necessary for effective dosage regimen of vancomycin in ovarian cancer patient to use these population parameters.