PD29 Systematic Review With Meta-analysis Of Pharmacokinetic Parameters Of Tyrosine Kinase Inhibitors Used In Chronic Myeloid Leukemia

Introduction Therapeutic drug monitoring (TDM) is a cost-effective tool to increase treatments’ efficacy and safety. Analyses of pharmacokinetics proprieties tyrosine kinase inhibitors (TKI) used for chronic myeloid leukemia (CML) can contribute towards effective TDM, development tailored treatments new dosing regimens. We aimed synthesize the available evidence on pharmacokinetic parameters imatinib, nilotinib, bosutinib, ponatinib in healthy individuals vs. CML patients. Methods Systematic searches were conducted PubMed, Scopus Web Science. included vivo studies addressing TKIs’ pharmacokinetics, including maximum observed concentration (Cmax), time (Tmax) half-life (t1/2). Meta-analyses event rates (mixed-effect models) performed interest: area under concentration-time curve from zero last measurable (AUC0-t) infinity (AUC 0-∞). Results presented as with 95 percent confidence intervals. Heterogeneity was assessed using chi-square I2 statistical tests considered significant when p<0.05 high I2>75 (Comprehensive Meta-Analysis v.2 Biostat-Englewood, NJ). Overall, 50 articles analyses (n=26 n=11 n=8 n=5 ponatinib). Most United States (46.0%), designed open-label trials (70.0%). Several interactions between TKI enzyme (ketoconazole, midazolam, aprepitant, metoprolol, grapefruit juice), proton pump (esomeprazole, lanzoprazole, omeprazole), antacids, H2 antagonists (famotidine) inducers (St. John’s, rifampicin) found (p<0.001). Given AUC Cmax patients hepatic/liver impairments currently TKI, strict therapeutic paramount maintain The study heterogeneity rated moderate (I2=75-90%) due limited number some drugs, different design, populations. Conclusions co-administration hepatic or inhibitors, antagonists, well failures requires caution additional monitoring. Further well-designed are needed strengthen this TKIs, namely bosutinib ponatinib.