Table 2.

Pharmacological characteristics of CDK4/6 inhibitors

	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

Chemical structures are available online at: https://pubchem.ncbi.nlm.nih.gov. Data about pharmacological characteristics of the three drugs are available online at: https://www.drugs.com

DLT dose-limiting toxicity, ESRD end-stage renal disease, IC50 half maximal inhibitory concentration, MTD maximum tolerated dose, NR not reported, RP2D recommended phase II dose

*Mild, moderate, and severe hepatic impairment refers to Child-Pugh classes A, B, and C, respectively