Pharmacodynamics of doxycycline

Cunha, Burke A.; Domenico, Philip; Cunha, Cheston B.

doi:10.1046/j.1469-0691.2000.00058-2.x

Cited by 92 publications

(78 citation statements)

References 7 publications

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“…Whether the higher level of doxycycline in vitro susceptibility is reflected clinically depends on additional PK/PD drug properties. The in vitro antibacterial activity of both doxycycline and tetracycline against S. pseudintermedius is time dependent, which is in agreement with previous findings for Staphylococcus aureus (40). According to the definition by LaPlante et al (24), in which a Ͻ3-log 10 CFU/ml reduction in colony count from that of the initial inoculum defines bacteriostatic activity, while a Ն3-log 10 CFU/ml reduction in colony count from that of the initial inoculum defines bactericidal activity, the activities of both drugs against S. pseudintermedius were regarded as bacteriostatic.…”

Section: Discussionsupporting

confidence: 92%

Pharmacodynamics of Doxycycline and Tetracycline against Staphylococcus pseudintermedius: Proposal of Canine-Specific Breakpoints for Doxycycline

et al. 2013

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Doxycycline is a tetracycline that has been licensed for veterinary use in some countries, but no clinical breakpoints are available for veterinary pathogens. The objectives of this study were (i) to establish breakpoints for doxycycline and (ii) to evaluate the use of tetracycline as a surrogate to predict the doxycycline susceptibility of Staphylococcus pseudintermedius isolates. MICs and inhibition zone diameters were determined for 168 canine S. pseudintermedius isolates according to Clinical and Laboratory Standards Institute (CLSI) standards. Tetracycline resistance genes were detected by PCR, and time-kill curves were determined for representative strains. In vitro pharmacodynamic and target animal pharmacokinetic data were analyzed by Monte Carlo simulation (MCS) for the development of MIC interpretive criteria. Optimal zone diameter breakpoints were defined using the standard error rate-bounded method. The two drugs displayed bacteriostatic activity and bimodal MIC distributions. Doxycycline was more active than tetracycline in non-wild-type strains. MCS and target attainment analysis indicated a certainty of >90% for attaining an area under the curve (AUC)/MIC ratio of >25 with a standard dosage of doxycycline (5 mg/kg of body weight every 12 h) for strains with MICs of <0.125 g/ml. Tetracycline predicted doxycycline susceptibility, but current tetracycline breakpoints were inappropriate for the interpretation of doxycycline susceptibility results. Accordingly, canine-specific doxycycline MIC breakpoints (susceptible, <0.125 g/ml; intermediate, 0.25 g/ml; resistant, >0.5 g/ml) and zone diameter breakpoints (susceptible, >25 mm; intermediate, 21 to 24 mm; resistant, <20 mm) and surrogate tetracycline MIC breakpoints (susceptible, <0.25 g/ml; intermediate, 0.5 g/ml; resistant, >1 g/ml) and zone diameter breakpoints (susceptible, >23 mm; intermediate, 18 to 22 mm; resistant, <17 mm) were proposed based on the data generated in this study.

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Section: Discussionsupporting

confidence: 92%

Pharmacodynamics of Doxycycline and Tetracycline against Staphylococcus pseudintermedius: Proposal of Canine-Specific Breakpoints for Doxycycline

et al. 2013

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“…In the present study, the C ss (8.3 ± 0.9 μg/mL) was above most inhibitory concentrations required for DC to exert a bacteriostatic effect against Staphylococcus aureus (4.8 μg/mL), Streptococcus pneumoniae (1.6 μg/mL), Pasteurella multocida (1.6 μg/mL), and Escherichia coli (8 μg/mL) (Cunha et al, 2000). This C ss was also 42 times higher than the MIC 90 for Mycoplasma gallisepticum (0.125 μg/mL) (Burch and Valks, 2002).…”

Section: Discussionmentioning

confidence: 48%

Pharmacokinetics and tissue depletion of doxycycline administered at high dosage to broiler chickens via the drinking water

Hsiao

Chang

Hsu

et al. 2016

Acta Veterinaria Hungarica

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The recommended use of doxycycline (DC) to broiler chicken is 100 mg/L via the drinking water and a 7-day withdrawal time (WDT). However, study of a higher dosage is desirable because of the possible increase of antimicrobial resistance and disease spectrum. Tissue DC residues exceeding the current maximum residue levels (MRL) was our major concern. Therefore, serum concentration and tissue depletion of DC hyclate after administration of 200 mg/L of DC in the drinking water for five consecutive days were studied. The steady-state DC concentration (8.3 ± 0.9 μg/mL) was reached on the third day of medication. The elimination constant (0.05 ± 0.01 1/h), half-life (14.9 ± 1.4 h), area under concentration versus time curve (81.0 ± 9.9 h·μg/mL) and mean residence time (22.7 ± 2.5 h) were obtained using a non-compartmental pharmacokinetic model. It was determined that the current 7-day WDT regulation was still legitimate for the kidney and liver as well as for the breast and leg muscles, which were estimated by linear regression analysis of the 99% upper distribution limit. The unregulated heart and gizzard were considered safe even when the lowest MRL of muscle (100 ng/g) was applied. While at the present time the extra-label use of drugs is only allowed under specific conditions, in the future it may become necessary to increase the general dosage of DC, and the current results suggest a safe range of DC hyclate in chicken; however, skin/fat tissue residues warrant further studies.

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“…The analysis presented here is the first to explore a population pharmacokinetic model of doxycycline concentrations following oral administration, which is an important step toward a population pharmacokinetic-pharmacodynamic model that could be used to critically examine and optimize doxycycline dose regimens. Although in vitro studies indicate that low concentrations of doxycycline kill in a time-dependent kinetic manner while higher concentrations kill in a concentration-dependent kinetic manner (13), at present this area has been insufficiently explored (2). Albeit this study is a step toward this, it is of note that this study presents a population pharmacokinetic model of doxycycline concentrations following the oral administration of doxycycline concentrations in healthy individuals, and the effect of disease status or sickness on doxycycline pharmacokinetics was not investigated here as all participants were healthy volunteers.…”

Section: Discussionmentioning

confidence: 99%

Population Pharmacokinetic Model of Doxycycline Plasma Concentrations Using Pooled Study Data

Hopkins

Wojciechowski

Abuhelwa

et al. 2017

Antimicrob Agents Chemother

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The literature presently lacks a population pharmacokinetic analysis of doxycycline. This study aimed to develop a population pharmacokinetic model of doxycycline plasma concentrations that could be used to assess the power of bioequivalence between Doryx delayed-release tablets and Doryx MPC. Doxycycline pharmacokinetic data were available from eight phase 1 clinical trials following single/ multiple doses of conventional-release doxycycline capsules, Doryx delayed-release tablets, and Doryx MPC under fed and fasted conditions. A population pharmacokinetic model was developed in a stepwise manner using NONMEM, version 7.3. The final covariate model was developed according to a forward inclusion (P Ͻ 0.01) and then backward deletion (P Ͻ 0.001) procedure. The final model was a twocompartment model with two-transit absorption compartments. Structural covariates in the base model included formulation effects on relative bioavailability (F), absorption lag (ALAG), and the transit absorption rate (KTR) under the fed status. An absorption delay (lag) for the fed status (FTLAG2 ϭ 0.203 h) was also included in the model as a structural covariate. The fed status was observed to decrease F by 10.5%, and the effect of female sex was a 14.4% increase in clearance. The manuscript presents the first population pharmacokinetic model of doxycycline plasma concentrations following oral doxycycline administration. The model was used to assess the power of bioequivalence between Doryx delayed-release tablets and Doryx MPC, and it could potentially be used to critically examine and optimize doxycycline dose regimens.

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Pharmacodynamics of doxycycline

Cited by 92 publications

References 7 publications

Pharmacodynamics of Doxycycline and Tetracycline against Staphylococcus pseudintermedius: Proposal of Canine-Specific Breakpoints for Doxycycline

Pharmacodynamics of Doxycycline and Tetracycline against Staphylococcus pseudintermedius: Proposal of Canine-Specific Breakpoints for Doxycycline

Pharmacokinetics and tissue depletion of doxycycline administered at high dosage to broiler chickens via the drinking water

Population Pharmacokinetic Model of Doxycycline Plasma Concentrations Using Pooled Study Data

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