SUMMARY

• Following once daily oral administration of CAPLYTA, lumateperone steady state is reached in about 5 days. Lumateperone steady-state exposure is approximately dose-proportional in the range of 3.5 mg to 56 mg (0.08 to 1.3 times the approved recommended daily dosage).¹
• A large inter-subject variability in lumateperone pharmacokinetic (PK) parameters was observed, with coefficients of variation for peak plasma concentration (C_max) and area under the concentration vs time curve (AUC) ranging from 68% to 97% at steady state.¹
• After CAPLYTA dosing, the absolute bioavailability of lumateperone capsules is about 4.4%. C_max of lumateperone is reached approximately 1-2 hours after CAPLYTA dosing.¹
• Protein binding of lumateperone is 97.4% at 5 μM (about 70-fold higher than therapeutic concentrations) in human plasma.¹
• The clearance of lumateperone is approximately 27.9 L/hour and the terminal half-life is about 18 hours after intravenous administration.¹

PRODUCT LABELING

Pharmacokinetics

Following once daily oral administration of CAPLYTA, lumateperone steady state is reached in about 5 days. Lumateperone steady-state exposure is approximately dose-proportional in the range of 3.5 mg to 56 mg (0.08 to 1.3 times the approved recommended daily dosage). A large inter-subject variability in lumateperone PK parameters was observed, with coefficients of variation for C_max (peak plasma concentration) and AUC (area under the concentration vs time curve) ranging from 68% to 97% at steady state.¹

Absorption

After CAPLYTA dosing, the absolute bioavailability of lumateperone is about 4.4%. C_max of lumateperone is reached approximately 1-2 hours after CAPLYTA dosing.¹

Effect of Food

Ingestion of a high-fat meal with CAPLYTA lowers lumateperone mean C_max by 33% and increased mean AUC by 9%. Median T_max was delayed about 1 hour (from 1 hour at fasted state to 2 hours in the presence of food).¹

Distribution

Protein binding of lumateperone is 97.4% at 5 μM (about 70-fold higher than therapeutic concentrations) in human plasma. The volume of distribution of lumateperone following intravenous administration is about 4.1 L/kg.¹

Elimination

The clearance of lumateperone is approximately 27.9 L/hour and the terminal half-life is about 18 hours after intravenous administration.¹

Metabolism

Lumateperone is extensively metabolized with more than twenty metabolites identified in vivo. After a single ¹⁴C-labeled oral dose, lumateperone and glucuronidated metabolites represent about 2.8% and 51% of the total plasma radioactivity, respectively. In vitro studies show that multiple enzymes, including but not limited to uridine 5'-diphospho-glucuronosyltransferases (UDP-glucuronosyltransferase, UGT) 1A1, 1A4, and 2B15, aldoketoreductase (AKR)1C1, 1B10, and 1C4, and cytochrome P450 (CYP) 3A4, 2C8, and 1A2, are involved in the metabolism of lumateperone.¹

Excretion

In a human mass-balance study, 58% and 29% of the radioactive dose was recovered in the urine and feces, respectively. Less than 1% of the dose was excreted as unchanged lumateperone in the urine.¹

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 7 October 2025.