Table 2. Excipient-target activities determined in vitro.

The targets are drawn from safety profiling assays generally used for determining off-target effects of drug candidates and marketed drugs. Functions are drawn from the Handbook of Pharmaceutical Excipients (64) except as noted. Examples of marketed drugs containing the excipient, and maximal excipient dosages occurring in any single formulation, are shown. Biochemical and radioligand binding data (IC₅₀) are unformatted; functional data (antagonism/inhibition, IC₅₀; agonism, half maximal effective concentration EC₅₀) are in bold in the Target column. Activity values are accurate to ±20%.

Excipient	Function	Structure	Example marketed drug	Highest excipient amount/dose	Target	Ki/IC50 Or EC50 (μM)
Aspartame	Sweetener		Purixan	450 mg†	NR1I2	13
Benzethonium chloride	Antimicrobial preservative; antiseptic; disinfectant		Ketalar/ketamine hydrochloride§	0.1%‡	ADORA3 ADRA1A DRD1 DRD3 ESR1 HRH3 PRG OPRM PDE4D PTGS2 ABCB11 SLC18A2 KCNH2	5.3 4.7 3.8 1.6 11 27 6.2 6.0 14 24 29 0.18 1.9
Benzoic acid	Antimicrobial preservative; therapeutic agent		Excedrin Migraine	25 mg/5 ml†	ABCB11 SLC18A2	260 18
Butylparaben	Antimicrobial preservative		Fexofenadine (children’s allergy)	8 mg/5 ml†	SLCO2B1 ADRA1A SLC6A2 SLC6A3 TBXA2R SLC18A2 SCN5A	39 16 20 18 19 6.6 33
Cetylpyridinium chloride	Antimicrobial preservative; antiseptic; surfactant; disinfectant; solubilizer; wetting agent		Dyazide	1.5 mg†	ADRA1A DRD1 DRD3 ESR1 HRH3 PRG OPRM1 PDE4D PTGS1 PTGS2 TBXA2R SLC18A2 KCNH2 SCN5A	6.4 4.8 0.55 18 13 4.5 5.1 13 7.5 2.5 3.4 0.73 1.3 34
Chloroxylenol	Antimicrobial preservative; antiseptic; disinfectant		Miconazole nitrate	0.1%‡	CHRM1 ADRA1A SLC18A2	9.9 14 0.79
Cysteine	Antioxidant*		Zyban	16.2 mg†	PTGS2	4.7
D&C Red No. 28	Colorant		Nexium 24HR	2.5 mg/5 ml†	SLCO2B1 ADRA1A DRD1 ADORA3 CHRM2 OPRM1 PDE3A PDE4D	0.60 0.48 0.59 0.48 0.68 0.82 0.13 0.94
Ethylparaben	Antimicrobial preservative		Clindamycin (pediatric)	2 mg/5 ml†	SLC18A2	22
FD&C Red No. 3	Colorant		Esomeprazole	2 mg/5 ml†	ACHE PDE3A PDE4D	0.42 0.092 0.32
FD&C Yellow No. 5 (Tartrazine)	Colorant		Pepcid Complete (tropical flavor)	652 mg†	DRD1 OPRM1 GABRA1	23 16 13
Methylene Blue	Colorant		Diurex Water Pills†	1%§	ACHE CHRM2 HRH3 KCNH2	0.090 0.19 0.88 27.5
Oleic acid	Emulsifying agent; skin penetrant		Verapamil	598.6 mg†	PTGS1 PTGS2 SLC18A2	6.7 3.5 4.7
Palmitic acid	Emulsifying agent; skin penetrant; tablet and capsule lubricant		Captopril	6 mg†	PDE3A PDE4D SLC18A2	4.1 6.6 4.4
Phenylmercuric acetate	Antimicrobial preservative; antiseptic		-	0.01%¶	DRD1 DRD3 SLC6A2 SLC6A3 CHRM1** SLC18A2 KCNH2	2.2 0.024 1.7 1.8 8.1 0.36 6.2
Propyl gallate	Antioxidant		Janumet XR	2 mg†	ALOX5 PTGS2 TY3H KDM4C FTO	0.43 7.2 1.9 39 3.0
Propylparaben	Antimicrobial preservative		Keppra	200 mg/5 ml†	SLC6A2 KDR LTA4H	30 24 260
Sodium lauryl sulfate	Anionic surfactant; detergent; emulsifying agent; skin penetrant; lubricant; wetting agent		Cetirizine	96 mg†	HTR1A ADORA3 CHRM1 ADRA1A DRD3 PRG PDE4D	15 15 29 15 18 15 23
Stearic acid	Emulsifying agent; solubilizing agent; tablet and capsule lubricant		Kariva	1203 mg/5 ml†	PDE3A PDE4D	3.1 6.7
Thimerosal	Antimicrobial preservative; antiseptic		Influenza vaccines multidose packaging	0.03%§	ADORA3 ADRA2A SLC18A2 DRD1 DRD3 5HT2b**	1.6 3.8 0.97 2.4 0.32 15
Ethyl mercury	Thimerosal major metabolite		NA	NA	DRD3 DRD5	0.21 0.15
Thymol	Antioxidant; antiseptic; cooling agent; disinfectant; flavoring agent; skin penetrant		Listerine†	0.01%#	CHRM1 ADRA1A SLC6A2 SLC18A2	14 26 28 25

^*From (65).

^†Oral.

^‡Auricular.

^§Intravenous.

^¶Topical.

^#Inhalation.

^**An agonist effect was observed.