ABSTRACT
The pharmacokinetics and bioavailability of hydrocortisone after rectal administration of a hydrocortisone acetate foam were determined after single and multiple dosing in healthy subjects as well as in patients with inflammatory bowel disease. Endogenous hydrocortisone was suppressed by dexamethasone administration. Plasma levels were compared with those observed after intravenous administration of hydrocortisone. Only a very small part of the rectal dose (100 mg) was absorbed; the mean absolute bioavailability was 3.1% in healthy volunteers and 4.5% in patients. There was substantial intersubject variability. Although maximum hydrocortisone levels after single or multiple doses were significantly higher (about 70%) in the patient group, the systemic bioavailability is very low so that the risk of systemic side effects after rectal administration of hydrocortisone acetate foam has to be considered very low.
Subject(s)
Hydrocortisone/analogs & derivatives , Hydrocortisone/administration & dosage , Hydrocortisone/pharmacokinetics , Rectum/metabolism , Administration, Rectal , Adult , Aged , Area Under Curve , Biological Availability , Drug Administration Schedule , Half-Life , Humans , Hydrocortisone/blood , Inflammatory Bowel Diseases/drug therapy , Intestinal Absorption , Metabolic Clearance Rate , Middle AgedABSTRACT
The commercially available betamethasone suspensions for injection used in this study have clearly shown quantitative differences in the combination of their easily hydrosoluble betamethasone esters and those difficult to dissolve in water, as well as in the shapes and sizes of their crystals. With regard to their influence on the endogenous cortisol production the two preparations have shown a highly deviating pharmaco-dynamic duration of action-corresponding to their different galenic composition (betamethasone phosphate/acetate approx. 7-8 days; betamethasone phosphate/dipropionate approx. 16-18 days). During the phase of suppression the reduced endogenous cortisol is largely compensated by the pharmaco-dynamic activity of the exogenous steroid.
Subject(s)
Betamethasone/pharmacology , Adolescent , Betamethasone/administration & dosage , Crystallization , Esters , Humans , Hydrocortisone/biosynthesis , Particle Size , SolubilityABSTRACT
The ultrastructural distribution of 14-C- and the 3-H-carbocromene in monkeys and rats showed a characteristic pattern in the coronary artery wall and the heart muscle. The radioactivity was found to be located on the coronary vessel wall mainly in the tunica media over the smooth muscle cells and in the myocardium over the contractile elements and the mitochondria.
