Physiologically-based modeling and simulation helped a drug sponsor anticipate the impact of smoking cessation on drug exposure levels and toxicity risk, avoiding the need for a costly clinical trial.
Schizophrenics are often heavy smokers, which can affect the metabolism of other drugs. With smoking prohibited in hospitals across most countries, a global pharmaceutical company developing a new anti-schizophrenia drug faced concerns about potential increases in drug exposure and ensuing toxicity should there be a need for hospitalization.
Elimination of the new drug candidate was mediated almost exclusively by the enzyme cytochrome P450 1A2 (CYP1A2). Cigarette smoking induces CYP1A2 in a dose-dependent manner; heavy smoking has been shown to dramatically increase the clearance of drugs metabolized by that pathway, such as caffeine (Tantcheva-Poór et al. 1999).