TABLE 3.

Plasma D-4F levels were dramatically different after oral or subcutaneous (SQ) administration but the concentration of D-4F in the feces and the total amount of D-4F excreted in the feces were similar regardless of whether the peptide was administered SQ or orally

D-4F Dose μg/mouse/day	Route of Administration	Plasma D-4F Levels	D-4F in Feces μg/gram feces	μg D-4F in Feces per 24 Hours per Mouse	% Dose Excreted
3	Oral	3.7 ± 2 ng/ml	0.14 ± 0.01	0.075 ± 0.019	2.5 ± 0.6
3	SQ	0.59 ± 0.1 μg/ml	0.27 ± 0.12	0.093 ± 0.06	3.1 ± 2
9	Oral	8.8 ± 8 ng/ml	5.5 ± 2.9	0.71 ± 0.79	7.9 ± 8.8
9	SQ	0.99 ± 05 μg/ml	7.8 ± 2.8	0.94 ± 0.48	10 ± 5
90	Oral	13 ± 4 ng/ml	24.3 ± 9.6	3.5 ± 1.5	3.9 ± 1.7
90	SQ	13.3 ± 0.6 μg/ml	20.0 ± 6.6	3.5 ± 1.5	3.9 ± 1.7
900	Oral	46 ± 1 ng/ml	252 ± 14	47 ± 8.3	5.2 ± 0.9
900	SQ	63.3 ± 4 μg/ml	315 ± 128	52 ± 36	5.8 ± 4.0

ApoE null female mice, 6–8 months of age were placed on a Western diet. After 2 weeks, the Western diet was continued and the mice were transferred to metabolic cages (n = 8–10 mice for each dose group and for each route of administration) and administered D-4F SQ or by addition to the drinking water (Oral) to give a dose of 3, 9, 90, or 900 μg of peptide per day. Feces and urine were discarded from the first 24 h of treatment. Feces and urine were collected from the second 24 h of treatment and analyzed for D-4F concentration and content as described in Materials and Methods. Immediately following the second 24 h period in the metabolic cages, the mice receiving the peptide in drinking water were deprived of water for 3 h and then allowed access to water containing peptide. The mice were allowed to drink the water containing their daily dose of peptide over a period of 3 h and were bled. Similarly, immediately following the second 24 h period in the metabolic cages, the SQ groups were injected with their daily dose of peptide and bled 2–3 h later. Plasma D-4F levels were determined as described in Materials and Methods. The values shown for plasma D-4F levels are the mean ± SD of three plasma samples randomly selected from each dose and each route of administration. The values shown for the fecal analyses are the mean ± SD.