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Pharmacokinetics and Safety of Olaparib in Patients with Advanced Solid Tumours and Renal Impairment
- Source :
- Clinical Pharmacokinetics, 58(9), 1165-1174. Adis International Ltd, Clinical Pharmacokinetics, 58(9), 1165. Adis International Ltd
- Publication Year :
- 2019
-
Abstract
- BACKGROUND: Olaparib, a potent oral poly(ADP-ribose) polymerase inhibitor, is partially renally cleared. We investigated the pharmacokinetics and safety of olaparib in patients with mild or moderate renal impairment to provide dosing recommendations. METHODS: This phase I open-label study assessed the pharmacokinetics, safety and tolerability of single-dose, oral 300-mg olaparib tablets in adults (aged 18-75 years) with solid tumours. Patients had normal renal function, or mild or moderate renal impairment (estimated creatinine clearance ≥ 81, 51-80 or 31-50 mL/min, respectively). Blood was collected for 96 h, and urine samples collected for 24 h post-dose. Patients could continue taking olaparib 300 mg twice daily for a long-term safety assessment. RESULTS: Overall, 44 patients received one or more doses of olaparib and 38 were included in the pharmacokinetic assessment. Patients with mild renal impairment had an area under the curve geometric least-squares mean ratio of 1.24 (90% confidence interval 1.06-1.47) and a geometric least-squares mean maximum plasma concentration ratio of 1.15 (90% confidence interval 1.04-1.27) vs. those with normal renal function. In patients with moderate renal impairment, the geometric least-squares mean ratio for the area under the curve was 1.44 (90% confidence interval 1.10-1.89) and for the maximum plasma concentration was 1.26 (90% confidence interval 1.06-1.48) vs. those with normal renal function. No new safety signals were detected in patients with mild or moderate renal impairment. CONCLUSIONS: In patients with mild renal impairment, the small increase in exposure to olaparib was not considered clinically relevant. In patients with moderate renal impairment, exposure to olaparib increased by 44%; thus, these patients should be carefully monitored and the tablet dose should be adjusted to 200 mg twice daily. CLINICAL TRIALS REGISTRATION: NCT01894256.
- Subjects :
- Adult
Male
medicine.medical_specialty
PHARMACOKINETICS
No-observed-adverse-effect level
Metabolic Clearance Rate
Urology
Renal function
Administration, Oral
Poly(ADP-ribose) Polymerase Inhibitors
Kidney
olaparib
Piperazines
Olaparib
03 medical and health sciences
chemistry.chemical_compound
polymerase inhibitor
0302 clinical medicine
Pharmacokinetics
Neoplasms
Medicine
Advanced Solid Tumours
Humans
Pharmacology (medical)
030212 general & internal medicine
Dosing
Renal Insufficiency
Renal impairment
Aged
Pharmacology
Medicine(all)
No-Observed-Adverse-Effect Level
business.industry
Area under the curve
INHIBITOR
Middle Aged
CANCER
Confidence interval
chemistry
Tolerability
030220 oncology & carcinogenesis
Phthalazines
Female
Safety
business
Subjects
Details
- ISSN :
- 11791926 and 03125963
- Volume :
- 58
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Clinical pharmacokinetics
- Accession number :
- edsair.doi.dedup.....0675a310cb6b40430804a775331f8fcc