テトラメチルピラジンの経皮パッチにおける薬物動態および組織分布に対するボルネオールの影響

Tetramethylpyrazine (TMP), a potent coronary vasodilator, enhances myocardial perfusion and shows promise for treating cardiovascular disorders. Its clinical utility is limited, however, by the short half-life of conventional tablets and injections, which necessitates frequent dosing. To overcome this drawback, we developed a transdermal patch that co-loadsTMP and borneol (BO-TMP). After optimization, patches containing 3% borneol as a permeation enhancer, exhibiting the highest cumulative penetration amount of TMP (6.80 mg·cm^-2 over 24 h) in vitro. Pharmacokinetic profiling revealed that borneol markedly improved TMP exposure. C_max rose from (1.96 ± 0.27) to (2.88 ± 0.72) mg/L, and AUC_0-t expanded from (47.73 ± 6.93) to (73.18 ± 13.86) mg/L*h in plasma; C_max rose from (12.99 ± 2.28) to (15.33 ± 4.24) mg/L, and AUC_0-t expanded from (220.86 ± 53.88) to (374.55 ± 111.84) mg/L*h in skin, C_max rose from (0.87 ± 0.12) to (6.20 ± 0.84) mg/L, and AUC_0-t expanded from (13.08 ± 3.35) to (79.80 ± 16.31) mg/L*h in heart when BO-TMP patches were administrated compared with TMP patches. Tissue distribution studies demonstrated that borneol redirected TMP distribution, shifting the order of tissue abundance from liver > kidney > brain > spleen > heart > lung to liver > kidney > heart > brain > spleen > lung, and thus enriched the drug at its therapeutic site. By selectively heightening cardiac exposure, the BO-TMP patch transform TMP into a cardiovascular-focused therapy, offering a convenient, long-acting dosage from with the potential to enhance efficacy and improve patient outcomes.