home > drugs a-z list > loxitane (loxapine) drug center > loxitane (loxapine) drug - clinical pharmacology

Pharmacodynamics

Pharmacologically, loxapine is a tranquilizer for which the exact mode of action has not been established. However, changes in the level of excitability of subcortical inhibitory areas have been observed in several animal species in association with such manifestations of tranquilization as calming effects and suppression of aggressive behavior.

In normal human volunteers, signs of sedation were seen within 20 to 30 minutes after administration, were most pronounced within 1 1/2 to three hours, and lasted through 12 hours. Similar timing of primary pharmacologic effects was seen in animals.

Absorption, Distribution, Metabolism, and Excretion

After administration of LOXITANE (loxapine) as an oral solution, systemic bioavailability of the parent drug was only about one third that after an equivalent intramuscular dose (25 mg base) in male volunteers. C _max for the parent drug was similar for the IM and oral administrations, whereas T _max was significantly longer for the IM administration than the oral administration (approximately 5 vs 1 hour). The lower systemic availability of the parent drug after oral administration as compared to the IM administration may be due to first pass metabolism of the oral form.

This is supported by the finding that two metabolites found in serum (8-hydroxyloxapine and 8-hydroxydesmethylloxapine) were formed to a lesser extent after IM administration of loxapine as compared to oral administration.

The apparent half-life of loxapine after oral and IM administration is approximately four hours (range, 1 to 14 hours) and 12 hours (range, 8 to 23 hours), respectively. The extended half-life for the IM administration as compared to the oral administration may be explained by prolonged absorption of loxapine from the muscle during the concurrent elimination process.

Loxapine is extensively metabolized, and urinary recovery over 48 hours resulted in recoveries of approximately 30% and 40% of an IM and orally administered loxapine dose as five metabolites.

Last reviewed on RxList: 12/8/2004
This monograph has been modified to include the generic and brand name in many instances.