Pharmacokinetics of clodronate in patients with metastatic breast cancer.

Pharmacokinetics of clodronate was studied in six breast cancer patients with only bone metastases. 14C-clodronate was administered intravenously (10 muCi/200 mg) and orally (20 muCi/400 mg) on separate occasions. Vc of clodronate averaged 6.3 +/- 3.0 (SD) 1 and Vdss 16.3 +/- 3.81 corresponding to the extracellular water volume. Distribution and elimination were fast with t1/2 alpha of 0.22 +/- 0.22 h and t1/2 beta of 2.3 +/- 0.9 h. The elimination occurred mainly by renal excretion of the unchanged drug CLP averaging 107 +/- 27 ml/min and CLR 80 +/- 18 ml/min. The protein unbound, free fraction in plasma was 64%. On the basis of urinary excretion data, there was a slow terminal elimination phase with a half-life of 12.8 +/- 6.9 h. Thus about 20% of the intravenous dose was retained in the body, most likely in the bones, 3 days after drug administration. About 75% of the intravenous dose was recovered in urine and 5% in feces. Based on cumulative excretion data into urine after both routes of administration, the bioavailability of oral clodronate was 1.9 +/- 0.4%. These findings correspond closely to those obtained in healthy volunteers in previous studies.

Trauma, renal vein thrombosis and subsequent nephrotic syndrome.

A case of kidney trauma with local and systemic consequences is given. The patient got a trauma to right kidney region. After a fortnights latency nephrotic syndrome developed. Radiological examinations one month after the trauma revealed a partially recanalized thrombus in the right renal vein. It turned out in renal biopsy that the underlying cause of the nephrotic syndrome was acute proliferative glomerulonephritis with typical humps in electronmicroscopy. In contralateral (non-traumatized) kidney there was in renal biopsy the same type of acute glomerulonephritis as well. The course of the renal lesion was documented by a series of renal biopsies which showed improving proliferative glomerulonephritis. The time course of the events and the bilateral histological changes suggest renal trauma as the cause of acute proliferative glomerulonephritis which is a new aspect.

Plasma levels and excretion of estrogens in urine in chronic lever disease.

Plasma levels of nonconjugated estrone (E1), estradiol-17beta (E2), and estriol (E3) and excretion of these estrogens in urine in conjugated and nonconjugated forms were measured by radioimmunoassay in 17 healthy males and 33 males with alcoholic liver disease. Patients with liver disease had significantly elevated plasma levels of E1 (74.2 +/- 8.0 SE versus 26.0 +/- 1.7 pg per ml, P less than 0.001), E2 (29.3 +/- 2.2 versus 23.3 +/- 2.0 pg per ml, P = less than 0.05), and E3 (11.5 + 1.9 versus 6.5 +/- 0.7 pg per ml, P less than 0.01). Excretion of total E1, E2, and E3 in urine was significantly increased in patients with liver disease; the increase was primarily in the nonconjugated fraction. Among those patients with chronic liver disease, the presence of ascites was associated with significantly higher plasma levels of E1 and excretion of larger amounts of E1 and E2 in urine. On the other hand, no differences were observed in the small number of patients with gynecomastia. A direct correlation between the plasma level or excretion of E1 or E2 and several liver function abnormalities was observed. The relative hyperestrogenemia we report here may account for some of the clinical observations in chronic liver disease.