Romanian Society of Pharmaceutical Sciences

« Back to Farmacia Journal 5/2024

OLANZAPINE AND FLUOROQUINOLONES ANTIBIOTICS: A NON CLINICAL STUDY OF DRUG-DRUG INTERACTIONS DUE TO CYP1A2 INHIBITION

ANA-ELENA CHIRALI 1, IULIA MARIA CIOCOTIȘAN 1, ANA-MARIA VLASE 2*, DANA MARIA MUNTEAN 1, LAURIAN VLASE 1

1 Department of Pharmaceutical Technology and Biopharmacy, Faculty of Pharmacy, “Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania
2 Department of Pharmaceutical Botany, Faculty of Pharmacy, “Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania

Download Full Article PDF

This study aimed to investigate the pharmacokinetic interaction between olanzapine and two fluoroquinolone antibiotics, known for their inhibitory effects on CYP1A2. The obtained results demonstrated that the concomitant administration of ciprofloxacin or norfloxacin with olanzapine significantly altered the pharmacokinetic parameters of olanzapine and its active metabolite, N-des-methyl olanzapine. Specifically, the maximum plasma concentration of olanzapine (Cmax) increased from 170.52 ± 107.27 ng/mL to 361.03 ± 186.96 ng/mL (after co-administration with ciprofloxacin) and 509.91 ± 259.80 ng/mL (after co-administration with norfloxacin). In addition, the total area under the curve (AUC0-∞) was significantly higher, increasing from 1601.60 ± 890.96 hr*ng/mL to 3589.32 ± 1334.15 hr*ng/mL (after co-administration with ciprofloxacin) and 5555.88 ± 2538.30 hr*ng/mL (after co-administration with norfloxacin). Similar trends were observed for its active metabolite, with a notable increase in Cmax and significant changes in clearance (Cl_F) and volume of distribution (Vz_F). These results confirm that both ciprofloxacin and norfloxacin significantly inhibit CYP1A2, leading to reduced clearance and increased systemic exposure to olanzapine and its active metabolite. This is the first non-clinical study evaluating the impact of these antibiotics on olanzapine metabolism, providing important information on potential drug-drug interactions in clinical practice.