Table 2.

Brain exposure to xenobiotics combined with Pgp inhibitors in preclinical studies.

Pgp Inhibitor (Mechanism of Action)	Dose	Time Lapse before Drug Administration	Drug Tested	Dose	Time Lapse before Brain Analysis	Increased Brain Parenchyma Penetration	Species	Reference
Cyclosporin A (Calcineurin inhibitor)			Anticancer drug
	50 mg/kg p.o	1 h	Paclitaxel	10 mg/kg i.v	24 h	3 times	Mice	[93]
	50 mg/kg p.o	1 h	Docetaxel	33 mg/kg i.v	24 h	2.3 times	Mice	[94]
			Antidepressant
	20 mg/kg i.p	1 h	Escitalopram	0.1 mg/kg i.p	30 min	>2 times	Mice	[95]
	20 mg/kg i.p	1 h	Escitalopram	1 mg/kg i.p	30 min	>1.75 times	Mice	[95]
	200 mg/kg i.p	1 h	Nortriptyline	10 mg/kg i.p	1 h	1.5 times	Rats	[96]
	25 mg/kg i.v	30 min	Imipramine	5 mg/kg i.v	4 h	1.84 times	Rats	[97]
			Opioid
	100 mg/kg i.p	1 h	Oxycodone	1 mg/kg s.c	2 h	1.4 times	Mice	[98]
Zosuquidar (MDR1 inhibitor)			Anticancer drug
	25–80 mg/kg p.o	1 h	Paclitaxel	10 mg/kg i.v	24 h	2.1–5.6 times	Mice	[99]
	25 mg/kg i.p	30 min	Imatinib	25 mg/kg p.o	1 h	2–3 times	Mice	[100]
Elacridar (MDR1 and BRCP inhibitor)			Anticancer drug
	25 mg/kg p.o	2 h	Paclitaxel	10 mg/kg i.v	24 h	5 times	Mice	[94]
	25 mg/kg p.o	2 h	Docetaxel	33 mg/kg i.v	24 h	3.6 times	Mice	[93]
	100 mg/kg p.o	2 h	Sunitinib	10 mg/kg p.o	1 h	12 times	Mice	[101]
	100 mg/kg p.o	15 min	N-desethyl sunitinib	5 mg/kg i.v	1 h	3.3 times	Mice	[102]
	5 mg/kg i.p	30 min	Lapatinib	100 mg/kg p.o	24 h	1.5 times	Rats	[103]
	100 mg/kg p.o	2 h 30 min	Vemurafenib	5 mg/kg p.o	4 h	3–5 times	Mice	[104]
	100 mg/kg p.o	2 h	Crizotinib	5 mg/kg p.o	4 h	2.2 times	Mice	[105]
	10 mg/kg i.v	30 min	Gefitinib	25 mg/kg p.o	2 h	4 times	Mice	[106]
Valspodar (MDR1 inhibitor)			Anticancer drug
	25 mg/kg p.o	1 h	Paclitaxel	10 mg/kg i.v	24 h	6.5 times	Mice	[93]
	25 mg/kg p.o	1 h	Docetaxel	33 mg/kg i.v	24 h	3.5 times	Mice	[94]
	10 mg/kg i.v	5 min	Vinblastine	brain perfusion	20 s	9.1 times	Rats	[107]
			Anti-inflammatory
	10 mg/kg i.v	5 min	Colchicine	brain perfusion	20 s	8.4 times	Rats	[107]
Verapamil (Calcium channel inhibitor)			Anticancer drug
	1 mg/kg i.v	5 min	Vinblastine	brain perfusion	20 s	3.7 times	Rats	[107]
			Anti-inflammatory
	1 mg/kg i.v	5 min	Colchicine	brain perfusion	20 s	3.7 times	Rats	[107]
			Antidepressant
	20 mg/kg i.p	1 h 30 min	Imipramine	5 mg/kg i.v	4 h	1.44 times	Rats	[97]
			Opioid
	3 mg/kg i.p	1 h	Oxycodone	1 mg/kg s.c	2 h	1.3 times	Mice	[98]

per os (p.o); intravenous (i.v); intraperitoneal (i.p); subcutaneous (s.c).