Transport and lymphatic uptake of biotherapeutics through subcutaneous injection

ABSTRACT The stimulating action of testosterone on the chick's comb can be inhibited by the subcutaneous injection of 0.1 mg of norethisterone or Ro 2-7239 (2-acetyl-7-oxo-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodecahydrophenanthrene), 0.5 mg of cortisol or progesterone, and by 4.5 mg of Mer-25 (1-(p-2-diethylaminoethoxyphenyl)-1-phenyl-2-p-methoxyphenyl ethanol). No dose response relationship could be established. Norethisterone was the most active anti-androgen by this test.

Download Full-text

THE THYMOLYTIC ACTIVITY OF 6- AND 9-HALOCORTICOIDS AND RELATED STEROIDS

Acta Endocrinologica ◽

10.1530/acta.0.0490262 ◽

1965 ◽

Vol 49 (2) ◽

pp. 262-270 ◽

Cited By ~ 2

Author(s):

Ralph I. Dorfman ◽

P. G. Holton ◽

Fred A. Kind

Keyword(s):

Double Bond ◽

Subcutaneous Injection ◽

Fluocinolone Acetonide ◽

Relative Potency ◽

Subcutaneous Route ◽

Adrenalectomized Rats

ABSTRACT Adrenalectomized rats were used for the determination of the relative potency of various 6- and 9-halo substituted corticoids administered subcutaneously or by gavage using thymus weightas the endpoint. By subcutaneous injection, fluocinolone acetonide was the most active corticoid at 700 times that of cortisol. This compound was also the most active corticoid by the gavage route and was judged to be 570 times as active as the standard cortisol. The introduction of the 16,17-acetonide and 16,17-acetone 21-acetate groups into 17α,21-dihydroxy-9α,11β-dichloropregna-1,4-diene-3,20-dione increased the activity by a factor of 42 and 100, respectively. The introduction of the δ1 double bond into 6α-fluoroprogesterone 16,17-acetonide caused an increase of 10-fold in thymolytic activity assessed by the subcutaneous route

Download Full-text

QUANTITATIVE RELATIONS IN THE AQUEOUS FLARE RESPONSE INDUCED BY α-MELANOCYTE STIMULATING HORMONE IN THE RABBIT EYES

Acta Endocrinologica ◽

10.1530/acta.0.0490166 ◽

1965 ◽

Vol 49 (1) ◽

pp. 166-176 ◽

Cited By ~ 2

Author(s):

K. Dyster-Aas ◽

C. E. T. Krakau

Keyword(s):

Subcutaneous Injection ◽

Great Variability ◽

Local Administration ◽

Aqueous Flare ◽

Melanocyte Stimulating Hormone ◽

Flare Response ◽

Stimulating Hormone

ABSTRACT The aqueous flare response (AFR) to MSH is induced in an increasing percentage of animals with increasing age. The great variability of the responses and the fact that local administration of MSH is not more efficient with lower doses than by subcutaneous injection indicate that the AFR is a complex result in which general factors play a part. The analysis of the variation of the responses has led to a procedure for testing the effect of different preparations.

Download Full-text

ANTI-OVULATORY ACTIVITY OF STEROIDS ADMINISTERED BY GAVAGE IN THE ADULT OESTRUS RABBIT

Acta Endocrinologica ◽

10.1530/acta.0.042s017 ◽

1963 ◽

Vol 42 (2_Suppl) ◽

pp. S17-S30

Author(s):

Fred A. Kind ◽

Ralph I. Dorfman

Keyword(s):

Dose Response ◽

Active Compound ◽

Subcutaneous Injection ◽

Response Curve ◽

Parent Compound ◽

Dose Response Curve ◽

Relative Potency ◽

Reference Standard ◽

Highly Active ◽

Dose Levels

ABSTRACT Thirty-seven steroids have been studied as orally effective inhibitors of ovulation in the mated oestrus rabbit. Norethisterone served as the reference standard and a dose response curve was established between the 0.31 and 1.25 mg dose levels. Nine highly active anti-ovulatory compounds are described listed in a decreasing order of potency with norethisterone having the arbitrary value of one: 6-chloro-Δ6-dehydro-17α-acetoxyprogesterone (35), 6α-methyl-Δ1-dehydro-17α-acetoxyprogesterone (≥ 10), 6-fluoro-Δ6-dehydro-17α-acetoxyprogesterone(9), 6-methyl-Δ6-dehydro-17α-acetoxyprogesterone (5), Δ6-dehydro-17α-acetoxyprogesterone (≥ 3), 6α-methyl-17α-acetoxyprogesterone (2.6), 6-chloro-Δ1,6-bisdehydro-17α-acetoxyprogesterone (≥ 2), 2-hydroxymethyl-17α-methyl-17β-hydroxyandrostan-3-one (≥ 2), and 6α-fluoro-16α-methyl-17α-acetoxyprogesterone (≥ 1.25). The anti-ovulatory activity of a compound was not related necessarily to the progestational activity of a compound nor to the anti-gonadotrophic activity as measured in parabiotic rats. 6-Chloro-Δ60dehydro-17-acetoxyprogesterone was as effective by gavage as previously shown by subcutaneous injection. 2-Hydroxymethyl-17α-methyl-17β-hydroxyandrostan-3-one was at least 2.5 times more active by gavage than by injection. While 17α-acetoxyprogesterone was a very weak anti-ovulatory steroid, modifications of the structure by addition of methyl or halogen at the 6α position with or without unsaturation greatly increased the activity. 6-Chloro-Δ6-dehydro-27α-acetoxyprogesterone was the most active compound in this series showing a relative potency of 3500 times that of the parent compound 17α-acetoxyprogesterone.

Download Full-text