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1.
APMIS ; 130(4): 197-205, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34978745

RESUMEN

Cutibacterium acnes has been associated with chronic prostatitis, which can potentially favor the appearance of tumors in the prostate. Prostatitis is difficult to treat, and the drug needs to be able to penetrate the prostate. The aim was to investigate the pharmacokinetics of clindamycin in the interstitial fluid of rat prostate using microdialysis. Microdialysis probes were recovered in vitro and in vivo. Clindamycin was administered at 80 mg/kg iv bolus for plasma and tissue pharmacokinetic experiments. A microdialysis probe was implanted in the prostate gland for collections over an 8-hour period. The pharmacokinetic parameters were determined by both compartmental and non-compartmental approaches. Penetration was determined as the ratio between the area under the curve and the time of the clindamycin measurement in the prostate. The recovery of the in vivo probes was 38.11 ± 1.14%. The plasma profile was modeled by a two-compartment pharmacokinetic model. Clindamycin presented a prostate/plasma ratio of 1.02, with free concentrations above the minimum inhibitory concentration for Cutibacterium acnes isolates. This was the first study that determined clindamycin free concentrations in the prostatic fluid of rats. These findings suggest that clindamycin may be an effective alternative for the treatment of prostatitis caused by Cutibacterium acnes.


Asunto(s)
Clindamicina , Prostatitis , Animales , Antibacterianos/farmacología , Clindamicina/farmacología , Clindamicina/uso terapéutico , Masculino , Pruebas de Sensibilidad Microbiana , Próstata , Prostatitis/tratamiento farmacológico , Ratas
2.
Biomed Chromatogr ; 34(11): e4977, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32852079

RESUMEN

Clindamycin is used for infections caused by Gram-positive and Gram-negative anaerobic pathogens and Gram-positive aerobes. Propionibacterium acnes is an important opportunistic microorganism of the human skin and is related to prostatitis. An LC-electrospray ionization-quadrupole time-of-flight-MS method was validated for determining clindamycin concentrations in plasma and prostate microdialysate. Clindamycin separation was carried out on a C18 column at 0.5 mL/min. The mobile phase employed gradient elution of formic acid and methanol. A mass spectrometer was operated in positive electrospray ionization mode to monitor ion 425.1784 and 253.1152 for clindamycin and cimetidine (internal standard), respectively. Linearity was obtained at 0.5-10.0 µg/mL (plasma) and 0.05-1.0 µg/mL (microdialysate) with coefficients of determination ≥0.999. The intra- and inter-day precision (coefficient of variation - CV%) values were ≤13.83% and 12.51% for plasma, respectively, and ≤10.90% and 9.35% for microdialysate, respectively. The accuracy was between 90.82% and 108.25% for plasma, and 96.97% and 106.98% for microdialysate. The present method was fully validated and applied to investigate clindamycin concentrations in both plasma and prostate by microdialysis in Wistar rats (80 mg/kg, intravenous). Because the penetration of antibiotics into the prostate may be restricted, this method allows us to investigate the prostate concentrations of clindamycin for the first time.


Asunto(s)
Cromatografía Liquida/métodos , Clindamicina/análisis , Próstata/química , Espectrometría de Masa por Ionización de Electrospray/métodos , Animales , Clindamicina/química , Clindamicina/farmacocinética , Límite de Detección , Modelos Lineales , Masculino , Microdiálisis , Próstata/metabolismo , Ratas , Ratas Wistar , Reproducibilidad de los Resultados
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