The aim of this study was to examine the clinical profile of statin-induced myalgia in patients with no apparent predisposing factors. Patients who reported muscle complaints that limited daily functioning during statin use were prospectively identified among the patients of Kuusankoski District Hospital and its catchment area, a population of about 100,000, between January 2003 and July 2004. Twenty patients in whom the muscle complaints were probably attributable to the use of a statin were included in this series. There were no cases of severe myopathy or rhabdomyolysis, and the highest creatine kinase value observed was only about 1900 U/l. Of the 18 patients that were evaluable for creatine kinase level, 5 (28%) did not exhibit elevation of creatine kinase and 6 (33%) showed a minor increase only. Following discontinuation of the statin, resolution of symptoms and normalisation of creatine kinase occurred in 11 of the 13 patients with elevated creatine kinase value as well as muscle complaints. Statins may cause clinically important muscle symptoms without inducing a marked creatine kinase elevation.Statins are well established as agents that reduce serum cholesterol concentrations and thereby decrease cardiovascular morbidity and mortality. Myopathy is one of the few serious adverse effects associated with the use of statins (Omar et al. 2001;Evans & Rees 2002;Thompson et al. 2003). Myopathy is usually defined as a proximal or generalised pain and/or weakness in skeletal muscles and a creatine kinase value higher than 10 times the upper limit of the normal range. Statin-induced myopathy can progress to rhabdomyolysis which can result in renal failure and death (Omar et al. 2001;Evans & Rees 2002;Thompson et al. 2003).Although the incidence rate of severe myopathy is very low, this adverse drug effect has considerable clinical importance in light of the widespread and expanding use of statins. Little is known about the molecular mechanisms of statin-associated myopathy. One popular view is that myopathy is associated with inhibition of HMG-CoA reductase in the muscle cells, which leads to decreased levels of cholesterol precursors and other products produced from mevalonic acid that are involved in posttranslational modification of essential regulatory proteins (Christians et al. 1998;Corsini et al. 1999;Liao 2002). The fact that statin myopathy is a much more rare event in clinical trials than in primary care settings may be explained by control of factors predisposing to myopathy and regular follow-up in trial patients (Thompson et al. 2003). The skeletal muscle toxicity of statins is at least partly dose-and concentration-dependent and the incidence of myopathy is considerably higher when high doses of statins are used or during concomitant use of agents that increase plasma statin concentrations (Davidson et al. 1997;Omar et al. 2001;Evans & Rees 2002;McKelvie & Dennett 2002). Drug interactions and other predisposing factors can be identified in many reported cases of severe myopathy. This stu...

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 bioavailability of the calcium and potassium salts of phenoxymethyl-penicillin (dose 38,000 I.U./kg) was investigated in eight healthy adult volunteers. Administration of the calcium salt as an aqueous oral mixture resulted in a mean peak plasma concentration of 8.52 mg/l (SD 1 X 96) and that of the potassium salt mixture in a concentration of 8.40 mg/ml (SD 2.61), p greater than 0.1. The median time-to-peak levels were 0.75 h and 1.0 h, respectively (p greater than 0.1). The mean AUC for the calcium salt mixture was 16.94 mg X h/l (SD 3.31) and for the potassium salt 15.84 mg X h/l (SD 4.76), p less than 0.09. These findings confirm that an aqueous mixture of calcium phenoxymethylpenicillin is equivalent to a mixture of potassium phenoxymethylpenicillin.

Ten patients with stable exercise-induced angina took part in this study. Isosorbide dinitrate and placebo sprays were administered in a double-blind, randomized crossover study. The dose of isosorbide dinitrate given was two squirts (= 2.5 mg) 2 min before testing. When taken before exercise it significantly improved (p less than 0.014) exercise tolerance. Significant (p less than 0.0005) ischaemic changes in the electrocardiogram also occurred. These effects occurred later than with placebo. Exercise time was prolonged with the active drug. The results of this study show that isosorbide dinitrate spray improves the exercise tolerance of patients with ischaemic heart disease.