Ciprofibrate in the therapy of type II hypercholesterolemia. A double-blind trial.

The hypolipidemic efficacy of ciprofibrate was evaluated in patients with type II hypercholesterolemia. Patients were randomized to placebo or ciprofibrate (50 mg or 100 mg/day) and, after a 6-week baseline period, received medication for a period of 12 weeks. Blood samples were analyzed every 2 weeks. Twenty patients completed the study (4 on placebo, 7 on 50 mg/day, and 9 on 100 mg/day ciprofibrate). The drug was well tolerated in all patients. Lipid values in the patients on active drug decreased and attained stable values after 4 weeks of treatment. Compared to baseline values, total and LDL cholesterol decreased 11% and 13% on the 50-mg dose whereas HDL increased 8%. Plasma triglyceride fell by 22%. In patients receiving 100 mg ciprofibrate, total and LDL cholesterol fell by 20% (334 leads to 269 mg/dl) and 24% (262 leads to 198 mg/dl), respectively. HDL increased 9.8% (51 leads to 56 mg/dl) and triglyceride decreased by 30% (102 leads to 69 mg/dl). Values in the placebo group remained stable. We conclude that once daily therapy with 100 mg ciprofibrate, is effective in reducing LDL levels in patients with type II hypercholesterolemia (mainly heterozygous FH) and that this decrease is paralleled by small rises in HDL.

Clinical effects and pharmacokinetics of racemic methadone and its optical isomers.

The respiratory and pupillary effects of oral l-, d-, and d,l-methadone were studied in healthy male volunteers 21 to 35 yr of age. The mean half-life of drug in blood was 22 hr for racemic methadone, 24 hr for l-methadone, and 25 hr for d-methadone. The effects of d-methadone were not significantly different from the placebo response at a 7.5 mg dose, whereas a 50 and 100 mg dose slightly depressed respiration in one subject each. Both 7.5 mg of l-methadone and 15 mg of d,l-methadone induced intense and sustained respiratory depression and miosis. The changes induced by l-methadone were of longer duration than those of d,l-methadone, lasting more than 72 hr in some subjects. Whole blood drug concentration correlated well with respiratory depression and miosis for l- and d,,l-methadone. The potency ratio of l-methadone to d,l-methdone, calculated from blood drug concentration data, was found to be 3.0 for respiratory depression and 2.7 for miosis. The antiduretic effect of 15 mg of d,l-methadone was investigated in three subjects and was found to persist for as long as measurements were taken, namely 11 and 12 hr in two subjects. d,l-Methadone administered frequently for pain may have cumulative effects on respiratory control and ability to excrete a water load.