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The pharmacokinetics of digoxin was studied in 14 healthy volunteers using concentrations measured radioimmunologically in the serum, saliva and urine. The subjects were given 0.75 mg of digoxin intravenously. Serum and saliva were obtained over a 72 hr period and urinary excretion rates over 6 or 7 days. Binding of digoxin to serum proteins was determined by ultracentrifugalization. A linear correlation between the serum and saliva concentrations was found. Salivary levels were equal to the unbound fraction in the serum. The half-lives of distribution did not differ between the serum and saliva. An erroneously short half-life of elimination was found in the serum, but in the saliva and urine it was found to be in the range previously reported. Salivary level measurements may be useful in pharmacokinetic studies and may have important clinical implications.

Estrogen receptor (ER) concentration of breast cancer tissue is important in predicting the response of each patient to hormonal, especially antiestrogen treatment. About half of the patients with ER rich tumours respond and only about 10% of the patients with ER poor tumours respond to antioestrogen treatment. Tamoxifen is a well known and widely used drug. Toremifene is a new antioestrogen, developed in Finland. At standard doses both compounds have comparable hormonal and antitumour effects, and there is no clear difference between the compounds in the affinity to ER. The value of ER in predicting the response to tamoxifen and toremifene therapy in ER positive breast cancer is significant. It is not known, however, if the role of ER remains the same with high dose toremifene. Although ERs are an important predictive factor, the antioestrogens evidently act through them only in part. As the prediction is correct in about half of the patients, other mechanisms must influence tumour growth regulation, such as the expression of oncogenes and the synthesis and activity of growth factors.

A new antioestrogenic antitumour compound toremifene was labeled with 11C or 3H. The tissue distribution and tumour uptake of the compounds in DMBA induced breast tumour bearing rats was investigated. 11C-toremifene was localized by gamma camera scintigraphy and tissue counting. 3H-Toremifene was determined by liquid scintillation counting after oxidizing the tissue samples. Toremifene was distributed to several tissues due to the lipophilicity and was not taken up specifically by the tumours to any great extent. However, the radioactivity of the tumours increased as a function of time although it declined e.g. in the liver. The accumulation to the tumour was a slow process and cannot be followed up reliably by such short half-life radionuclides as 11C. The tumour uptake properties of toremifene resemble those of tamoxifen and several other oestrogen receptor binding compounds. These substances have limited use in diagnosing and imaging oestrogen receptor rich breast tumours in man.

Combinations of interferons (IFNs) and cytostatic drugs were studied in subrenal capsule assay (SRCA) using fresh human ovarian cancer samples. Slight tumour growth inhibition was observed with IFN-alpha and IFN-gamma. The effect was more pronounced if combination IFN-alpha + IFN-gamma was used. Cytostatic drug combination cyclophosphamide + cisplatin + doxorubicin (combination I) was more effective than interferons, and combination methotrexate + tegafur (combination II) was about equal to IFN-alpha. When IFN-alpha was given together with cytostatic drugs, the antitumour effect was diverse: both synergistic and antagonistic effects were found, as well as no evidence of interaction. IFNs did not increase the toxicity of cytostatic drugs. If there is a good correlation between SRCA and clinical results, the combination of IFNs and cytotoxic drugs should be used clinically in connection with a predictive test.

The clinical effects of oral oxazepam and placebo as premedicants were tested in a double-blind study in 40 gynaecological patients. The gas chromatographically measured concentrations of the active, unconjugated forms of oxazepam in the plasma were correlated with the clinical effects of oxazepam, assessed both subjectively and objectively. The insertion of an intravenous cannula was significantly more difficult (p less than 0.001) in the placebo premedicated group. However, there was no significant difference between the two groups in the cutaneous temperature of the left forefinger. Of the eleven parameters tested there was a significant difference between the oxazepam and placebo group in the quality of sleep on the night before operation (p less than 0.05) and in the degree of preoperative sedation (p less than 0.01). The combined results of the eleven parameters of the oxazepam group also differed positively significantly from the placebo group (p less than 0.01). There was no obvious relationship between the plasma concentration and clinical effect of oxazepam.

Incentive proposals for fertility control have stimulated considerable debate and only narrowly conceived trials. As a result, there exists a tendency to dismiss almost offhandedly the entire concept of using material incentives to further contraceptive practice before any have been adequately tried. Moreover, a majority of proposals thus far have been characterized by a search to uncover the "one best way" to circumvent the myriad frustrations encountered in attempting to reduce birthrates in traditional societies.