1 The absolute bioavailability of morphine from oral aqueous solution, a controlled release oral tablet (MST-Continus) and a controlled release buccal tablet has been investigated in six healthy volunteers. 2 Analysis of plasma samples for morphine and its active metabolite morphine-6-glucuronide (M6G) was by means of a differential radioimmunoassay technique. Absolute bioavailability for morphine was estimated to be 23.9% after oral solution, 22.4% after MST-Continus and 18.7% after the buccal tablet. Maximum plasma morphine concentrations were seen at 45 min (oral solution), 2.5 h (MST) and 6 h (buccal). 3 There was no difference in the amount of M6G appearing in plasma after intravenous, oral or buccal administration but the mean ratio of AUCs for M6G: morphine in plasma after intravenous morphine was 2: 1 compared with 11: 1 after oral and buccal morphine.

High levels of BNP are synthesised and secreted by the transplanted human ventricle, and the transplanted ventricle may be an important source of circulating BNP. The significant positive association between ventricular BNP and time after transplant suggests a possible self compensatory mechanism or functional adaptation of the transplanted heart which may be beneficial to ventricular function.

After injection of [4-14C]norethisterone or norgestrel labelled with 14C in the ethynyl group into rabbits, 45 % and 57\m=.\4% of the radioactivity was excreted in the urine, mostly within 2 days. Although small amounts of radioactivity were excreted in the expired air of rabbits receiving norgestrel, little metabolism of the ethynyl group occurred. Radioactivity in plasma declined quickly after injection and 24 hr. later less than 0\m=.\5 % of the dose remained in the circulation. Up to 5 hr. after injection large amounts of radioactivity were found in liver, kidney, intestine and bile; a large proportion of the dose appeared to undergo an entero-hepatic circulation. Although the concentration in fat and muscle was low the total amount in these tissues may approach 5%. The uterus contained a high concentration of radioactivity suggesting that this tissue may bind the progestins or their metabolites. By 24 hr. the amount of radioactivity in the tissues had markedly decreased. Small amounts of radioactivity crossed the placenta of pregnant animals near term and small amounts were found in the foetus and amniotic fluid. Within 3 hr. of the injection at least half of the radioactivity in the tissues was in a conjugated form and considerable metabolism of the injected progestins had occurred. Little, if any, norethisterone or norgestrel was present in the tissues. The metabolites of norethisterone were mainly polar compounds showing that hydroxylation of the steroid had occurred, whereas the metabolites of norgestrel appeared to be similar to the compounds produced by partial or complete reduction of the \g=a\,\g=b\-unsaturated ketone grouping in ring A.