Table 1.

Pharmacologic Parameters of Integrase Inhibitors

Drug	Formulations	Dosing	Metabolism	Elimination Half-life	Protein Binding	Protein-adjusted Inhibitory Concentration	PK Parameters (CV%)	Food effects	Dosing in renal/ hepatic impairment
Raltegravir1,2,3	400mg tablet 100mg chewtabs 25mg chewtabs	Adults: 400mg bid Children: 6mg/kg bid	UGT1A1	~9 hours	83%	IC95=16 ng/mL	Geometric Mean AUC0–12h= 6900ng*h/mL C12h=68.5ng/mL (212)	Dosed without regard to meals Film-coated tab: AUC increased two-fold with high fat meal Chew tabs: AUC decreased slightly with fat	No dose adjustments warranted in renal or hepatic impairment
Elvitegravir,4, 5,6,7,8,9,10	150mg tablet “Quad” tablet (combination with tenofovir 300mg, emtricitabine 200mg, cobicistat 150mg)	Adults: 150mg daily with 150mg cobicistat daily or 100mg ritonavir daily	CYP3A4 (major) UGT1A1/3 (minor)	~3 hours alone ~9 hours boosted with 100mg ritonavir or 150mg cobicistat	>99%	IC95=45 ng/mL	With ritonavir: AUC0–24h = 22500ng*h/ml (23.4) C24h= 410ng/ml (40.5) Cmax= 2500ng/ml (32.1) With cobicistat: AUC0–24h = 27000ng*h/mL (29.4) C24h = 490ng/mL (52.9) Cmax=2660ng/mL (27.6)	Administer with food. AUC increased 34% with low fat meal and 87% with high fat meal	Severe renal impairment data not yet available, No dose adjustment for mild to moderate hepatic impairment
Dolutegravir11, 12, 13, 14	50mg tablet “572-Tri” tablet (combination with abacavir 600mg and lamivudine 300mg)	Adults: 50mg daily	UGT1A1 (major) CYP3A (minor)	~12–15 hours	>99%	IC90=64 ng/mL	AUC0–24h = 43400ng*h/ml (20) C24h=830ng/ml (26) Cmax=3340ng/ml (16)	Dosed without regard to meals despite increases in tmax, AUC, and Cmax with food	No dose adjustment for severe renal impairment, No dose adjustment for mild-moderate hepatic impairment