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

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 2538.30hr*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. RezumatAcest studiu a avut drept obiectiv investigarea interaciunii farmacocinetice dintre olanzapin i dou antibiotice din clasa fluorochinolonelor, cunoscute pentru efectele lor inhibitoare asupra CYP1A2.Rezultatele obinute au demonstrat c administrarea concomitent de ciprofloxacin sau norfloxacin cu olanzapin a modificat semnificativ parametrii farmacocinetici ai olanzapinei i ai metabolitului su activ, N-desmetil olanzapina.Mai precis, concentraia plasmatic maxim a olanzapinei (Cmax) a crescut de la 170,52 107,27 ng/mL la 361,03 186,96 ng/mL (dup co-administrarea cu ciprofloxacin) i 509,91 259,80 ng/mL (dup co-administrarea cu norfloxacin).n plus, aria total sub curb (AUC0-) a fost semnificativ mai mare, crescnd de la 1601,60 890,96 hr*ng/mL la 3589,32 1334,15 hr*ng/mL (dup co-administrarea cu ciprofloxacin) i 5555,88 2538,30 hr*ng/mL (dup co-administrarea cu norfloxacin).Tendine similare au fost observate pentru metabolitul su activ, cu o cretere notabil a Cmax i modificri semnificative ale clearance-ului (Cl_F) i volumului de distribuie (Vz_F).Aceste rezultate confirm faptul c att ciprofloxacina, ct i norfloxacina inhib semnificativ CYP1A2, ducnd la reducerea clearance-ului i la creterea expunerii sistemice la olanzapin i metabolitul su activ.Acesta este primul studiu non-clinic care evalueaz impactul acestor antibiotice asupra metabolismului olanzapinei, oferind informaii importante privind potenialele interaciuni medicamentoase n practica clinic.