Fenoldopam increased renal blood flow in a dose-dependent manner compared with placebo, and, at the lowest dose, significantly increased renal blood flow occurred without changes in systemic blood pressure or heart rate. These findings will be useful in designing future studies exploring the role of fenoldopam in preventing or treating renal failure in patients who are not hypertensive.

Anticoagulation was more predictable with argatroban than with heparin as measured by ACT and aPTT, with comparable safety profiles.

Although mean blood clearance and renal clearance values progressively declined with increasing degree of renal impairment, based on the safety profile and the fact that the administered dose was double the standard dose used for MRI purposes, there appears to be no need for dose reduction in this population.

SUMMARYPurpose: To compare the pharmacokinetics of USL255, a once-daily extended-release (ER) formulation of topiramate (TPM), with Topamax (immediate-release TPM) in healthy subjects after oral dosing and evaluate the effect of food on USL255 bioavailability and pharmacokinetics. Methods: This randomized, single-center, open-label, cross-over design study had three dosing periods separated by 21 days of washout between treatments. Thirtysix volunteers received single doses of USL255 (200 mg) in fasted and fed conditions and two doses of Topamax (100 mg) administered 12 h apart. TPM plasma samples were analyzed by liquid chromatography-mass spectroscopy. Pharmacokinetic parameters were calculated by noncompartmental methods. Key Findings: USL255 fasted pharmacokinetic parameters [point estimate (90% confidence interval, CI) compared to Topamax] were: relative bioavailability (F ) 91.2% (84-99%), peak plasma concentration (C max ) USL255/Topamax-ratio 59% (53-65%), time to reach C max (t max ) 19.5 ± 7.2 h, accumulation ratio (R ac ) 3.9 ± 1.2, effective half-life (t 1/2,eff ) 55.7 ± 19.9 h, terminal half-life (t 1/2,z ) 80.2 ± 14.2 h, and peak-occupancy-time (POT) 12.1 ± 4.0 h. Although the F and C max were unaffected by food, R ac and t 1/2,eff increased to 4.9 ± 0.9, and 72.5 ± 15.4 h, respectively. In contrast to t 1/2,z, t 1/2,eff reflects absorption rate; therefore, USL255's t 1/2,eff was significantly longer than Topamax's t 1/2,eff (37.1 ± 6.5 h). Significance: Although bioequivalent to Topamax in extent of absorption, USL255 had a slower absorption rate as reflected in its lower C max and longer t max , larger POT and longer t 1/2,eff , and similar R ac values to that of Topamax (q12 h). This relative flat plasma profile allows for once-daily dosing with diminished fluctuations in TPM plasma levels. In addition, neither USL255's peak nor extent of plasma exposure of TPM was affected by food.

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Low-dose transdermal estradiol gel 0.1% is an effective treatment for relief of vasomotor symptoms, as well as signs of vulvar and vaginal atrophy, associated with menopause. Estradiol gel 0.1% offers multiple dosing options to individualize patient therapy, including the lowest available effective dose (0.25 mg estradiol, delivering 0.003 mg/d estradiol) to treat the vasomotor symptoms of menopause.

The pharmacokinetics of intravenously administered recombinant human interleukin-10 (rHuIL-10) were evaluated in 18 subjects with creatinine clearances (Clcr) between 2.7 and 116.7 mL/min/1.73 m2. Serum samples for rHuIL-10 were obtained over a 48-hour period after a single 25 micrograms/kg i.v. bolus infusion. AUC, total body clearance (Clp), and steady-state volume of distribution (Vdss) were derived by compartmental methods. Analysis of serum concentrations showed statistically significant group differences for log-transformed AUC and original scale Clp (p < 0.01). The AUC and effective half-life increased, while the mean Clp of rHuIL-10 decreased as renal function declined. A linear relationship between AUC and Clcr as well as Clp and Clcr demonstrates that the disposition of rHuIL-10 is altered in subjects with renal insufficiency. No serious adverse events were noted.