Pharmacokinetics and pharmacodynamics of alirocumab and evolocumab

	Alirocumab	Evolocumab
Pharmacokinetics
Absorption	Median Tmax: 3 to 7 days	Median Tmax: 3 to 4 days
	Estimated absolute bioavailability: 85%	Estimated absolute bioavailability: 72%
	Cmax: 1.54±1.02 ng/mL following 150 mg dose	Cmax: 18.6±7.3 ug/mL following 140 mg dose 59.0±17.2 ug/mL following 420 mg dose
	AUC: 129±35.7 mg • day/L following 75 mg dose	AUC: 188±98.6 day • ug/mL following 140 mg dose 924±346 day • ug/mL following 420 mg dose
Distribution	0.04 to 0.05 L/kg	3.3 (0.5)* L
Metabolism and elimination	Specific metabolism studies were not conducted, because the antibodies are proteins. The antibodies are expected to degrade to small peptides and individual amino acids.	Specific metabolism studies were not conducted, because the antibodies are proteins. The antibodies are expected to degrade to small peptides and individual amino acids.
	At low concentrations, the elimination is predominately through saturable binding to target (PCSK9), while at higher concentrations the elimination is largely through a nonsaturable proteolytic pathway.	At low concentrations, the elimination is predominately through saturable binding to target (PCSK9), while at higher concentrations the elimination is largely through a nonsaturable proteolytic pathway.
	Effective half-life of 17 to 20 days. When coadministered with a statin, the half-life is 12 days.	Effective half-life of 11 to 17 days.
Pharmacodynamics
	Following a single subcutaneous administration of 75 or 150 mg, maximal suppression of free PCSK9 occurred within 4 to 8 hours.	Following single subcutaneous administration of 140 or 420 mg, maximum suppression of circulating unbound PCSK9 occurred by 4 hours. A mean nadir in LDL-C lowering response occurs by 14 and 21 days following 140 or 420 mg dose, respectively. Subcutaneous regimens of 140 mg every 2 weeks and 420 mg once monthly were equivalent in average LDL-C lowering. LDL-C lowering efficacy was sustained with continued use, in measurements made over 112 weeks.
	Unbound PCSK9 concentrations returned toward baseline when antibody concentrations decreased below the limit of quantitation.	Unbound PCSK9 concentrations returned toward baseline when antibody concentrations decreased below the limit of quantitation. No rebound in PCSK9 or LDL-C above baseline was observed during the washout of evolocumab.

AUC: exposure as measured by the area under the concentration × time curve; Cmax: maximum plasma concentration; PCSK9: proprotein convertase subtilisin/kexin type 9; Tmax: time to maximum plasma concentration.

* Standard deviation.

References:

Chung JE. Clinical pharmacology review PRALUENT (Alirocumab). U.S. Food and Drug Administration 2014.
Suryanarayana Sista JE. Clinical phramacology review REPATHA (Evolocumab). U.S. Food and Drug Administration 2014.
Evolocumab injection. US Food & Drug Administration (FDA) approved product information. Revised July, 2016. Available on-line at http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm.
Alirocumab injection. US Food & Drug Administration (FDA) approved product information. Revised October, 2015. Available on-line at http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm.
Evolocumab (Repatha) Summary of Product Characteristics; European Medicines Agency. Revised March 3, 2017. Available on-line at http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003766/WC500191398.pdf.
Alirocumab (Praluent) Summary of Product Characteristics; European Medicines Agency. Revised November 18, 2016. Available on-line at http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003882/WC500194521.pdf.

Graphic 109030 Version 3.0

خرید پکیج

Pharmacokinetics and pharmacodynamics of alirocumab and evolocumab