Table 2.
Pharmacokinetic characteristics of PARP inhibitors.
| Olaparib | Niraparib | Rucaparib | |
|---|---|---|---|
| Posology | 300 bid | 300 mg | 600 bid |
| Bioavailability | NA | 73% | 30–45% |
| AUC 0-24 | 42,000 h ng/mL | NA | 1690 h ng/mL |
| Cmax | 58,000 ng/mL | 3 h | 1940 ng/mL |
| Tmax | 1–3 h | NA | 1.9 h |
| Plamatic Clearence | 8.6 L/h | 16.5 L/h | 13.9–18.4 L/h |
| Volume of Distribution | 167 L | 1311 L | 113–262 L |
| Half-life | 11.9 h | 48-51 h | 25.9 h |
| Co-Administration with Food | Food assumption delays Tmax of about 2 h |
No influence | After a highly lipidic meal, Cmax is increased by 20% and AUC of 38%, while Tmax is delayed by 2.5 h |
| Plasmatic Protein Binding | Dose-dependent: bound fraction decreases from 91% at 1 microg/mL concentration to 82% to qo microg/mL and to 70% at 40 microg/mL | 83% | 70.2% |
| Metabolism | CYP3A4/5 are enzymes primarily responsible for metabolism | Carboxilestherasis are the enzymes primarily responsible for metabolism | CYP2D6 and CYP1A2 e CYP3A4 are the enzymes primarily involved in metabolism |
| Substrate of | P-gp (clinically non-significant) | P-gp, BRCP, MATE1/2 (clinically non-significant) | P-gp and BCRP |
| Cytochromes and Transporters Inhibition | Induction of CYP1A2, 2B6 e 3A4 | Inhibition of MATE1/2 e and mild inhibition of OCT1 | Moderate inhibition of CYP1A2 |
| Cytochromes and Transporters Inhibition | Moderate inhibition of CYP3A, P-gp, BCRP, OATP1B1, OCT1, OCT2, OAT3, MATE1, MATE2K | None | Mild inhibition of CYP2C9, CYP2C19, CYP3A E P-gp |
| Renal Impairment | Severe renal impairment (ClCr < 30 mL/min): not recommended | Severe renal impairment (ClCr < 30 mL/min): not recommended | Severe renal impairment (ClCr < 30 mL/min): not recommended |
| Moderate renal impairment (CrCl 31–50 mL/min): dose reduction to 300 mg × 2 | Moderate renal impairment (CrCl 31–50 mL/min): no dose adjustment | Moderate renal impairment (CrCl 31–50 mL/min): no dose adjustment | |
| Mild renal impairment (ClCr 51–80 mL/min): no dose adjustment | Mild renal impairment (ClCr 51–80 mL/min): no dose adjustment | Mild renal impairment (ClCr 51–80 mL/min): no dose adjustment | |
| Hepatic Impairment | Mild or moderate hepatic impairment (child pug A or B): no dose adjustment | Mild or moderate hepatic impairment (child pug A or B): no dose adjustment | Mild or moderate hepatic impairment (child pug A or B): no dose adjustment |
| Severe hepatic impairment (child pug C): not recommended | Severe hepatic impairment (child pug C): not recommended | Severe hepatic impairment (child pug C): not recommended |