Pharmacodynamics of uniform versus nonuniform warfarin dosages.

STUDY OBJECTIVE: To compare the pharmacodynamics of uniform versus nonuniform warfarin dosages. DESIGN: Prospective, randomized, crossover study. SETTING: Anticoagulation clinic. SUBJECTS: Twenty healthy subjects who had the extensive metabolizer cytochrome P450 (CYP) genotype of 2C9*1/*1 or CYP2C9*1/*3. INTERVENTION: Subjects received either warfarin 5.75 mg once/day (two 1-mg tablets plus one and a half 2.5-mg tablets) as part of the uniform dosage group or warfarin 7.5 mg/day on Mondays and Fridays and 5 mg/day on each of the remaining days of the week as part of the nonuniform dosage group. Subjects received the first regimen for 17 days, had a 2-week washout period, and then were switched to the other regimen for another 17 days. MEASUREMENTS AND MAIN RESULTS: During both treatment periods, international normalized ratios (INRs) were checked daily using a fingerstick method. Any changes in concomitant drug therapy, including over-the-counter and supplement products, as well as health status were recorded. The Scheffe post hoc test revealed no significant differences in mean INR values obtained during receipt of the two dosage regimens. In both dosage groups, variation in the INR became more pronounced as INR values increased. No adverse events (i.e., major or minor bleeding) or changes in drug therapy were reported during the study. CONCLUSION: Our findings suggest that it is safe to use a nonuniform dosage regimen of warfarin to reach a target INR range. With both uniform and nonuniform regimens, close monitoring remains important to ensure that patients remain within the desired INR range.

The effect of oral pleconaril on hepatic cytochrome P450 3A activity in healthy adults using intravenous midazolam as a probe.

Pleconaril is a viral capsid inhibitor under evaluation for treatment of infections caused by rhinoviruses and enteroviruses. This study evaluated the effect of pleconaril on hepatic cytochrome P450 (CYP) 3A activity as assessed by intravenous (IV) midazolam. Healthy adults received oral pleconaril 400 mg 3 times daily for 16 doses. Single-dose, IV midazolam 0.025 mg/kg was administered before and during pleconaril administration. Midazolam and pleconaril plasma concentrations were assayed by LC/MS/MS. Bioequivalence was assessed by least squares geometric mean ratios (LS-GMR) with 90% confidence intervals (90% CIs) for the measured midazolam pharmacokinetic parameters. Sixteen subjects were enrolled, and 14 subjects completed the study. Pleconaril decreased midazolam AUC(0-infinity) 28% and increased systemic clearance 39%. LS-GMR (90% CI) were 0.718 (0.674-0.765) and 1.392 (1.307-1.483), respectively. Plasma pleconaril concentrations steadily increased over time. Observed changes in midazolam AUC(0-infinity) and systemic clearance suggest that oral pleconaril increased hepatic CYP3A activity in healthy adults.

An evaluation of the atkins' diet.

Low-carbohydrate (LC) weight-reducing diets are popular choices for self-dieters. Eighteen adults (BMI >/= 25 kg/m(2)) were enrolled in this short-term longitudinal study to evaluate dietary intake and weight on their "usual" diets and LC diet. Subjects were instructed to follow the first two phases of the diet described in Dr. Atkins' New Diet Revolution (2 weeks each). Total daily intake of calories and nutrients were calculated from 3-day food diaries. Body weight was measured at the end of each 2-week diet session. All enrolled subjects completed the study (age = 39.8 +/- 8.1 years, BMI = 36.6 +/- 6.6 kg/m(2)). Mean caloric intakes were 1400 +/- 472 kcal/day (Induction diet) and 1558 +/- 490 kcal/day (Ongoing Weight Loss diet) both p