No abstract

The steady-state pharmacokinetics of tamoxifen and its metabolites was studied in sixteen patients with advanced mammary cancer. Patients were randomized to receive tamoxifen given as Tamofen, Leiras, or as Nolvadex, ICI, 20 mg twice daily for 16 weeks in a cross-over study. Plasma and urine samples were analyzed during one dose interval (12 h) after treatment for 8 and 16 weeks. The concentrations of tamoxifen, N-desmethyltamoxifen, N,N-desdimethyltamoxifen, and metabolite Y were determined in plasma and the areas under the plasma level curves were calculated. 4-Hydroxytamoxifen was not found in plasma. In urine samples only tamoxifen and N-desmethyltamoxifen were above the detection limits even though metabolite Y was also analyzed after acid hydrolysis. There were no statistically significant differences in the concentrations of tamoxifen and its metabolites between the two preparations. The results of nonresponders did not differ from those of responders. Liver metastases had no effect on the metabolism of tamoxifen.

No abstract

The serum concentration of salbutamol was determined in 29 pregnant women during oral treatment (4 mg five times per day) and in seven during intravenous infusion (6-30 pgimin) because of premature labour. The concentration of salbutamol was determined by combined gas-liquid chromatography mass spectrometry. The mean concentration of serum salbutamol was twice as high during intravenous trcatment (24; SD 9 ngiml)? than during oral treatment (12; SD 3 mg/ ml). During oral treatment: the salbutamol lcvels were not correlated to maternal height, weight or the incidence or severity of side-effects. The serum concentrations of salbutamol in patients with twin pregnancies did not differ from those with singleton pregnancies. After stopping intravenous treatment, serum salbutamol levels remained high for several hours and oral treatment can be started 4-611 after stopping intravenous infusion.

The bioavailability of folic acid and trimethoprim was investigated from a combination preparation of folic acid (0.25 mg) and trimethoprim (100 mg) in ten healthy adult volunteers. Peroral administration of the preparation resulted in a mean peak plasma concentration of trimethoprim 1.09 mg/l (SEM 0.06). The AUC values for trimethoprim were 12.42 mg.h/l and 12.77 mg.h/l corresponding to combination preparation and plain trimethoprim, p greater than 0.1. After administration 0.25 mg folic acid in the combination preparation, there was a significant rise in serum folic acid concentrations. The AUC from 0-8 hours was 199.8 nmol.h/l (SEM 8.1) and 166.3 nmol.h/l (SEM 14.2) corresponding to combination preparation and plain trimethoprim, p less than 0.001. A loading dose of folic acid 10 mg was given intramuscularly 24 hours before drug intake. This new type of formulation of trimethoprim and folic acid has been developed in order to prevent in long-term use the adverse haematological effects induced by trimethoprim alone.