Pharmacokinetics and tissue distribution of 3,4-diaminopyridine in rats.

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Ishida N, Kondo Y, Chikano Y, Kobayashi-Nakade E, Suga Y, Ishizaki J, Komai K, Matsushita R

Pharmacokinetics and tissue distribution of 3,4-diaminopyridine in rats.

Biopharm Drug Dispos. 2019 Sep;40(8):294-301. doi: 10.1002/bdd.2203.

PubMed ID
31419315 [ View in PubMed
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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.

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