Colestipol-induced hepatotoxicity.

A 65-year-old man with type IIa dyslipidemia who received flavored colestipol granules 2 scoops/day for 3 months developed asymptomatic hepatotoxicity. Several of his liver enzymes were elevated 10 times the upper limit of normal. One week after discontinuing colestipol, serum transaminases fell dramatically, with some returning to normal limits. Four weeks after colestipol was discontinued, all liver function tests were normal. Rechallenge was not attempted. Other potential causes of hepatocellular injury were evaluated. Bile acid-binding resins commonly are administered to treat type IIa dyslipidemia. Despite extensive use of the resins, significant elevations of transaminase levels are rare. Because the exact mechanism of bile acid resin-induced hepatotoxicity is unknown, high-risk patients may require liver function test monitoring and education on hepatotoxic side effects.

The use of alternate-day lovastatin in hypercholesterolemic men.

OBJECTIVE: To quantitate the therapeutic effects of alternate-day lovastatin on serum lipoprotein values in a small group of men with primary hypercholesterolemia. DESIGN: Retrospective review of medical, pharmacy, and laboratory records. A paired Student's t-test was performed on absolute changes in lipoprotein values with an a priori p value less than or equal to 0.05 being statistically significant. SETTING: A lipid clinic within a tertiary care Department of Veterans Affairs Medical Center. PATIENTS: Twenty men (mean age 62.5 +/- 8.3 y) with mean +/- SD baseline low-density lipoprotein cholesterol (LDL-C) concentration of 161.3 +/- 21.9 mg/dL and triglyceride concentrations below 400 mg/dL. INTERVENTION: All patients had been prescribed lovastatin 20 mg every other day. MAIN OUTCOME MEASURES: The mean absolute and percent changes in lipoprotein values from baseline for patients receiving lovastatin 20 mg every other day and the percentage of patients attaining a target mean LDL-C concentration as defined by the National Cholesterol Education Panel Adult Treatment Panel II guidelines. RESULTS: Mean +/- SD total cholesterol and LDL-C were significantly reduced by 32.4 +/- 17.8 (14.0% +/- 7.8%) and 34.1 +/- 14.6 mg/dL (21.5% +/- 9.7%), respectively. No significant changes were seen in high- density lipoprotein cholesterol or triglycerides. Four of 20 patients (20%) attained a goal LDL-C concentration. CONCLUSIONS: Lovastatin 20 mg every other day may effectively lower LDL-C in some elderly men, and target LDL-C concentrations may be obtained in some patients.

Effect of calcium channel blockers on theophylline disposition.

Twelve healthy subjects received a single oral dose of theophylline, 5 mg/kg alone, and after 7 days of oral verapamil, 120 mg every 8 hours, diltiazem, 90 mg every 8 hours, and nifedipine, 20 mg every 8 hours, in randomized crossover fashion. Mean theophylline oral clearance decreased 18% and 12% after verapamil and diltiazem, respectively (p less than 0.05). No significant change in theophylline oral clearance was observed after nifedipine. Increases in mean theophylline half-life were observed after verapamil (10.8 +/- 3.2 hours) and diltiazem (9.9 +/- 2.4 hours) (p less than 0.05) but not after nifedipine (8.6 +/- 2.4 hours) when compared with control (8.6 +/- 1.9 hours). Apparent volume of distribution was unchanged. Urinary excretion data showed that the relative formation rate constants of 3-methylxanthine and 1,3-dimethyluric acid were decreased during verapamil and diltiazem (p less than 0.05) but not during nifedipine. No change in 1-methyluric acid excretion was observed. Increases in urinary elimination of unchanged theophylline were observed after verapamil, diltiazem, and nifedipine. The modest reduction in theophylline clearance observed after verapamil and diltiazem is not likely to produce clinically significant increases in theophylline concentrations in most patients.