The Effect of Renal Impairment on the Pharmacokinetics and Safety of Talazoparib in Patients with Advanced Solid Tumors
| Autor: | Anna Plotka, Sunil Babu, Sarina Anne Piha-Paul, Chandrasekar Durairaj, Diane D. Wang, Justin Hoffman, H. Hirte, Cristiano Ferrario, Haihong Shi, Jayeta Chakrabarti |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
Cmax Urology Renal function 030226 pharmacology & pharmacy 03 medical and health sciences 0302 clinical medicine Pharmacotherapy Pharmacokinetics Neoplasms medicine Humans Pharmacology (medical) Dosing Original Research Article Renal Insufficiency Adverse effect Pharmacology business.industry Tolerability 030220 oncology & carcinogenesis Renal physiology Area Under Curve Phthalazines business Glomerular Filtration Rate |
| Zdroj: | Clinical Pharmacokinetics |
| ISSN: | 1179-1926 0312-5963 |
| Popis: | Background Pharmacokinetic (PK) studies suggest that talazoparib is primarily eliminated unchanged via renal excretion. The current study investigated how varying degrees of renal impairment may affect the PK of talazoparib, and evaluated the safety and tolerability of talazoparib, in patients with advanced solid tumors with/without renal impairment. Methods Patients with advanced solid tumors and normal renal function or different degrees of renal impairment measured by estimated glomerular filtration rate (eGFR: mild = 60–89, moderate = 30–59, severe = 15–29 mL/min/1.73 m2) were enrolled in this open-label, non-randomized, phase I study. Talazoparib was administered orally at 0.5 mg/day for 22 days. Primary PK parameters included the area under the plasma concentration-time curve from 0 to 24 h (AUC0–24) and maximum observed plasma concentration (Cmax) at steady state (Day 22). Safety and tolerability were also investigated. Results Thirty-four patients were enrolled. At Day 22, compared with patients with normal renal function (n = 9), patients with mild (n = 9), moderate (n = 8), or severe (n = 8) renal impairment had a 12.2%, 43.0%, and 163.3% increase in talazoparib AUC0–24, and a 11.1%, 31.6%, and 89.3% increase in talazoparib Cmax, respectively. Talazoparib was generally well tolerated, and overall there were no notable differences in the treatment-emergent adverse event profile across renal function groups. Conclusions Exposure to talazoparib increased with worsening renal impairment. Overall, this study confirms current dosing recommendations in patients with mild and moderate renal impairment (1 mg/day and 0.75 mg/day, respectively) and indicates that a lower starting dose of 0.5 mg/day should be considered for patients with severe renal impairment. Clinical Trials Registration NCT02997163. Supplementary Information The online version contains supplementary material available at 10.1007/s40262-020-00983-y. |
| Databáze: | OpenAIRE |
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