. Author manuscript; available in PMC: 2021 Mar 15.

Published in final edited form as: Science. 2020 Jul 24;369(6502):403–413. doi: 10.1126/science.aaz9906

Table 4. Pharmacokinetics parameters of excipients.

Shown are pharmacokinetic parameters in rats of excipients after i.v. (1 mg/kg) and oral administration (cetylpyridinium chloride, 1 mg/kg; butylparaben, 10 mg/kg; FD&C Red No. 3, 1 mg/kg; D&C Red No. 6, 1 mg/kg; propyl gallate, 10 mg/kg). Diethyl phthalate and thimerosal pharmacokinetic data were obtained from the literature, as noted. MDCK-LE P_app is the apparent permeability measured in the Madin-Darby canine kidney permeability assay. AUC, area under curve; %F, bioavailability; N.D., not determined; d.n., dose normalized.

Excipient	Target	IC₅₀ (μM)	MDCK-LE P_app (×10⁻⁶ cm/s)	t_1/2 from i.v. dose (hours)	i.v. AUC (nM-hour) 0–24 (d.n.)	Oral AUC (nM-hour) 0–last (d.n.)	Oral C_max (nM)	%F
Butylparaben	TBXA2R	19	8.3	N.D.^*	N.D.^*	N.D.^*	<2.6	N.D.^*
CetyIpyridinium chloride	DRD3	0.55	<0.5	9.7	15,972	4,052	260	5.4
FD&C Red No. 3	PDE3A	0.092	<0.5	3.4	4,826	32	16.9	0.7
D&C Red No. 6	SLCO1B1	3.1	<1.2	6.9	30,511	776	164	2.5
Diethyl phthalate	PDE4D2	16	–	1.0^†	553^†	350^†	253^†	N.D.^†
Propyl gallate	COMT	0.015	11.7	4.9	6908	N.D.^*	<8.9	N.D.^*
Thimerosal	DRD3	0.32	–	24.2^‡	N.D.	N.D.	30 to 40 ng/g^‡ (70 to 105 nM)	N.D.

Only a single time point had values above the LOQ, so a t_1/2 and an AUC cannot be calculated.

^†

From (66).

^‡

From (42). In the case of thimerosal, Hg concentration was measured in the primate brain (ng/g) after intramuscular injection.