The Metabolism of 4-14c Prednisolone

Abstract

The urinary excretion of radioactivity after oral administration of 4-14c prednisolone was studied in a patient already receiving large daily doses of non-radioactive prednisolone. The radioactive metabolites in the urine were fractionated by various chromatographic procedures and the following radioactive compounds were identified: prednisolone; prednisone; 11\g=b\:17\g=a\:20\g=b\:21-tetrahydroxypregna-1:4-dien-3-one; 17\g=a\: 20\g=b\:21 -trihydroxypregna-1:4-diene\x=req-\ 3:11-dione; 3\g=a\: 11\g=b\:17\g=a\:21-tetrahydroxy-5\g=b\-pregnan-20-one;3\g=a\:17\g=a\:21-trihydroxy-5\g=b\-pregnane-11:20-dione. The significance of these findings is discussed.Although about 90% of the radioactivity administered as 4-14C prednisolone (lly8:17oc:21-trihydroxypregna-l:4-diene-3:20-dione) is excreted in the urine within 48 hr [Sandberg & Slaunwhite, 1957], only about 10% of the administered dose can be accounted for as known metabolites [Caspi & Pechet, 1957]. Moreover, while Gray, Green, Holness & Lunnon [1956] and Vermeulen [1956a-c] found no evidence for the presence of tetrahydrocortisone (3oc:17a:21-trihydroxy-5/3-pregnane-ll:20-dione) and tetrahydrocortisol (3a:llJ8:17a:21-tetrahydroxy-5jß-pregnan-20-one) in the urine of patients treated with non-radioactive prednisone or prednisolone, Caspi & Pechet [1957] have recently reported the isolation of the partially reduced product 17a:21-dihydroxypregn-l-ene-3:ll:20-trione as well as 20 mg tetrahydrocortisol and 3-4 mg allotetrahydrocortisol from the urine of a patient who had received a total of 940 mg prednisone (17a:21-dihydroxypregna-l:4-diene-3:ll:20-trione) during 16 days.This paper describes further investigations of the nature of the metabolites of 4-14C prednisolone. MATERIALS AND METHODS MaterialsA male patient aged 54 years, suffering from scleroderma and who had received 80 mg prednisolone/day orally in four divided doses for 4 days, was given 0-6 ixc (4 mg) 4-14C prednisolone orally in dilute ethanol. Urine specimens were collected for the periods 8, 16, 24 and 48 hr after administration of radioactive prednisolone. The specimens were stored without preservative at about 10°C and worked up immediately on completion of collection.

Evaluation of human intestinal absorption data and subsequent derivation of a quantitative structure–activity relationship (QSAR) with the Abraham descriptors

“…The names of drug and drug‐like compounds and related data are listed in Table 1 and 2. The absorption data was collected and evaluated from 244 papers 1–5, 8–12, 18–251. The following information concerning human drug absorption was recorded from the literature: absorption data given from the literature;oral bioavailability or absolute bioavailability;percentage of cumulative urinary excretion of unchanged drug and its metabolites following oral and intravenous administration;percentage of metabolites in urine or first‐pass effect following oral and intravenous administration;percentage of unchanged drug in urine following oral and intravenous administration;percentage of excretion of drug in bile following oral and intravenous administration;percentage of cumulative excretion of drug in feces following oral and intravenous administration;total recovery of drug in urine and feces following oral and intravenous administration;single dose level in mg or mg/kg and daily oral dose in mg. …”

Clinical Pharmacokinetics of Prednisone and Prednisolone

“…and their biological relevance is largely unknown (Caspi & Pechet 1957;Frey Fl & Frey BM 198); Siaunwhile & Sandberg 1961: Vermeulen 1959. At that time only limited informat ion was required about the pharmacokinetics and metabolism of new xenobiotics.…”

Influence of prednisolone on craniofacial and long bones in growing rats: A cephalometric and peripheral quantitative computed tomographic analysis

“…A number of studies have reported the mechanism of glucocorticoidinduced bone fragility, however, the issue has not been fully elucidated. Generally from 70 to 100 per cent of prednisolone administrated orally is absorbed in gut, which acts on target tissue cells mediating bloodstream 24,25) . In a previous in vitro study, glucocorticoids were shown to cause an increase in osteoblast and osteocyte apoptosis and a decrease in osteoblast differentiation in mice 26) .…”