A 45-year-old male with schizoaffective disorder has been stable on clozapine 500 mg daily for three years, with consistent trough levels between 380-420 ng/mL. He smokes approximately one pack of cigarettes per day. During a recent hospitalization for pneumonia, he was unable to smoke for 10 days. On hospital day 8, he develops marked sedation, orthostatic hypotension, excessive sialorrhea, and a new-onset seizure. An emergent clozapine level returns at 1,180 ng/mL. Which of the following best explains the pharmacokinetic mechanism underlying this clinical scenario?