Table 2 Pharmacological characteristics of CDK4/6 inhibitors
From: Are all cyclin-dependent kinases 4/6 inhibitors created equal?
Palbociclib (pd-0332991; ibrance, pfizer) | Abemaciclib (ly2835219; verzenio, lilly) | Ribociclib (lee011; kisquali, novartis) | |
|---|---|---|---|
Chemical structure |
|
|
|
Ic50 (nm) | |||
Cdk4-cyclin d1 | 11 | 2 | 10 |
Cdk6-cyclin d1-2-3 | 15 | 10 | 39 |
Absorption | Increased with high-fat, high-calorie food | NR | NR |
Distribution | 2583 L | 690.3 L | 1090 L |
Metabolism | Liver (cyp3a and sult2a1) | Liver (cyp3a4) | Liver (cyp3a4) |
Excretion | Feces (~74%) | Feces (~81%) | Feces (~69%) |
Urine (~18%) | Urine (~3%) | Urine (~23%) | |
Bioavailability | 46% | 45% | NR |
Time to peak (hours) | 6–12 | 8 | 1–4 |
Half-life elimination (hours) | 29 ± 5 | 18.3 | 30–55 |
Protein binding | ~85% | 93–98% | ~70% |
Mtd/rp2d | 125/125 mg/day on a 21-of-28-day schedule | 200 mg twice daily | 900/600 mg/day on a 21-of-28-day schedule |
Dlts | Neutropenia | Fatigue | Neutropenia, asymptomatic thrombocytopenia, mucositis, pulmonary embolism, hyponatremia, QTcF, prolongation (> 500 ms), increased creatinine |
Route of administration | Oral | Oral | Oral |
Recommended dose | 125 mg once daily for 21 days, followed by 7 days off, repeat every 28 days | 150 mg twice daily | 600 mg once daily for 21 days, followed by 7 days off, repeat every 28 days |
Dose modifications | |||
Renal impairment | |||
Crcl > 15 ml/min | No dosage adjustament | No dosage adjustament | No dosage adjustament |
Crcl ≤ 15 ml/min | NR | NR | NR |
Esrd | NR | NR | NR |
Hepatic impairment* | |||
Mild/moderate | No dosage adjustament | No dosage adjustament | No dosage adjustament |
Severe | Reduce dose to 75 mg | Reduce dose to once daily | Reduce dose to 400 mg |
