Determinação da penetração prostática de clindamicina por microdiálise em ratos Wistar

Abstract

The prostatitis is considered a set of disease which assails the prostate, which can be caused by infectious microbial agents such pathogen evolved with the vulgar acne. This microorganism has been identified in prostatitis and related to the development of prostatic tumors. The clindamycin was the subject of study due to its effects on this microorganism. The microorganisms combated by the presence of antimicrobials free concentrations which can penetrate the infectious site and reach sufficient concentrations in this biophase, better related to the pharmacological effect than the employment of total plasmatic concentrations. In this way, our study previously performed the development of a bioanalytical method by high performance liquid chromatography coupled to tandem mass spectrometry, to the clindamycin determination in the plasmatic matrix as much as the prostate microdialysate, substantiating to comply with the analytical performance requirements. The microdialysis probes were previously calibrated, in vitro by dialysis and retrodialysis (flow of 1.0 and 2.0 µL/min) and in vivo throughout retrodialysis (1.0 µL/min). The clindamycin was administered in Wistar rats with doses of 80 mg/kg by intravenous route. Plasma samples and from the prostate microdialysate were obtained for 8 hours. Pharmacokinetic parameters were determined by non-compartmental and compartmental analysis employing the Phoenix (WinNolin) software. The relation prostate/plasma was obtained considering the area under the curve (AUC) from the free concentration profile versus tissue and AUC from the total plasma profile versus tissue, corrected by the free fraction of clindamycin [AUC free tissue/(fu.AUCplasma, total)], where fu is the clindamycin free fraction in the rat plasma (fu = 0.325). The developed analytical methodology has been validated and presented itself as selective, linear, precise, and accurate, without matrix effect and with analytical stability within the established standards. The recovery rates of microdialysis probes in vitro employing dialysis and retrodialysis for the flow of 1.0 ?L/min ranged from 42.87 ± 1.94% to 45.13 ± 1.27%, and in the flow at 2.0 ?L/min of 32.30 ± 1.54% to 35.87 ± 2.04%. In vivo recovery was 38.11 ± 1.14%. The plasmatic pharmacokinetic was modeled by the pharmacokinetic model of two compartments. The AUC was 58.53 ±14.78 h.mg/L and 19.40 ±4.40 h.mg/L for plasma and prostate microdyalisate. The penetration factor of clindamycin at prostate microdyalisate was 1.02. Concentration of free clindamycin exceeded the minimum inhibitory concentrations to P. acnes described in the literature for prostate isolates. Clindamycin could have been suggested as an option for studies evolving prostatitis with the presence of P.acnes. [resumo fornecido pelo autor]