| Abstract: | Lambert‐Eaton myasthenic syndrome (LEMS) is characterized by muscle weakness, amyotrophy, easy fatigability, and depressed tendon reflexes. 3,4‐Diaminopyridine (3,4‐DAP) is the recommended therapy for the treatment of LEMS. However, estimations of 3,4‐DAP pharmacokinetics in human and animals, such as rats, are rarely reported because 3,4‐DAP is an orphan drug for the treatment of a very rare disease (LEMS). In particular, little is known about its tissue distribution. Therefore, the pharmacokinetics of 3,4‐DAP were studied, with particular focus on tissue distribution, in rats. After intravenous administration of 3,4‐DAP to rats, the half‐life of 3,4‐DAP was 15.9 ± 3.9 min and the volume of distribution at steady‐state was 2.8 ± 0.7 L/kg. The tissue‐to‐plasma partition coefficient (Kp) was high in the kidney, heart, and muscle. In addition, with increased steady state plasma concentration (Css), a tendency toward increased Kp was found in most tissues. In the muscle, a likely target region of 3,4‐DAP in LEMS patients, the Kp was higher than in the plasma. Furthermore, more than 68% of 3,4‐DAP was distributed to the muscle as determined by the ratio of 3,4‐DAP distribution calculated from the apparent volumes of distribution. Hence, 3,4‐DAP may provide for more effective and long‐lasting effects. |
