RESUMEN
This study aimed to compare the pharmacokinetic (PK) and safety profiles of 2 fenofibric acid formulations under fasting and fed conditions. The reference was a 135 mg capsule, while the test was a 110 mg enteric-coated tablet. This randomized, open-label, two-sequence, two-period crossover phase 1 clinical trial was conducted in healthy Korean men. Sixty participants were enrolled in each of the fasting and feeding groups. Blood samples were collected 72 hours after drug administration. PK parameters were calculated using a non-compartmental method with Phoenix WinNonlin®. A total of 53 and 51 participants from the fasting and feeding groups, respectively, completed the study. The geometric mean ratio and 90% confidence intervals of the maximum concentration (Cmax) and area under the concentration-time curve to the last measurable plasma concentration were 0.9195 (0.8795-0.9614) and 0.8630 (0.8472-0.8791) in the fasting study and 1.0926 (1.0102-1.1818) and 0.9998 (0.9675-1.0332) in the fed study, respectively. The time to reach Cmax of the enteric-coated tablet compared to that of the capsule was extended by 1 and 3 hours under fasting and fed conditions, respectively. In conclusion, enteric-coated tablets have a higher bioavailability than capsules. In addition, the enteric-coated tablet was smaller than the capsule, making it easier for patients to swallow. Trial Registration: Clinical Research Information Service Identifier: KCT0007177, KCT0003304.
Asunto(s)
Antibacterianos/aislamiento & purificación , Enoil-ACP Reductasa (NADH)/antagonistas & inhibidores , Inhibidores Enzimáticos/aislamiento & purificación , Compuestos Heterocíclicos de 4 o más Anillos/aislamiento & purificación , Penicillium/química , Staphylococcus aureus/efectos de los fármacos , Antibacterianos/química , Antibacterianos/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Compuestos Heterocíclicos de 4 o más Anillos/química , Compuestos Heterocíclicos de 4 o más Anillos/farmacología , Concentración 50 Inhibidora , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Modelos Moleculares , Estructura Molecular , Staphylococcus aureus/enzimologíaRESUMEN
An highly quaternary and unprecedented dispiro compound, verrulactone C, with the known compound, altenuisol, were isolated from a culture broth of the fungal strain Penicillium verruculosum F375 and their structures were established by various spectral analysis. Verrulactone C and altenuisol showed FabI-selective inhibition. Especially altenuisol had the high correlation between FabI-inhibition and whole cell antibacterial activity against Staphylococcus aureus and MRSA with MICs of 8-32µg/mL.
Asunto(s)
Antibacterianos/farmacología , Enoil-ACP Reductasa (NADH)/antagonistas & inhibidores , Inhibidores Enzimáticos/farmacología , Lactonas/farmacología , Penicillium/química , Compuestos de Espiro/farmacología , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/enzimología , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Enoil-ACP Reductasa (NADH)/metabolismo , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/aislamiento & purificación , Lactonas/química , Lactonas/aislamiento & purificación , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Compuestos de Espiro/química , Compuestos de Espiro/aislamiento & purificación , Relación Estructura-ActividadRESUMEN
New dimeric compounds of alternariol class, verrulactones A and B, were isolated from a culture broth of the fungal strain Penicillium verruculosum F375 and their structure were established by various spectral analysis. Verrulactones A and B strongly inhibited Staphylococcus aureus enoyl-ACP reductase with IC(50) of 0.92 and 1.41 µM, respectively, and also showed antibacterial activity against S. aureus and MRSA with MICs of 8 and 16 µg/mL, respectively.