Assessment of the effects of renal impairment on the pharmacokinetics of the soluble guanylate cyclase activator cinaciguat after a single intravenous dose.

This open-label, parallel-group, single-dose study assessed the safety and pharmacokinetics of cinaciguat, a novel soluble guanylate cyclase activator in clinical development for the treatment of acute decompensated heart failure, in individuals with mild, moderate, or severe renal impairment compared with individuals with normal renal function. Cinaciguat was administered as a 100 µg/h continuous infusion over 4 hours. Plasma concentrations were determined by high-performance liquid chromatography coupled with mass spectrometry. Renal function had only minor effects on the pharmacokinetics of cinaciguat. The apparent volume of distribution at steady state was slightly increased in individuals with renal impairment. The total body clearance from plasma showed a slight tendency to increase with progression of renal impairment, which can be explained by an increased hematocrit in individuals with renal impairment. No relevant influence was found on the terminal half-life. The fraction of cinaciguat unbound in plasma was very low (<1%) in all groups. Pharmacokinetic variability tended to be somewhat increased in individuals with renal impairment. Adverse events were mostly mild, and their incidence was similar in all groups. In conclusion, cinaciguat, a promising drug candidate for the treatment of acute decompensated heart failure, will not require dose adjustment based on renal function.

Optimizing wound healing in the face after laser abrasion.

BACKGROUND: Laser resurfacing is a popular procedure to improve the physical signs of photoaging. In addition to improvements in treatment modalities, optimizing posttreatment regimens will enhance patient care. OBJECTIVE: Our purpose was to evaluate the efficacy of two forms of wound care for the face after laser abrasion. METHODS: Forty-two patients received full-face laser resurfacing at two clinics by using either the UltraPulse carbon dioxide (CO(2)) laser (Coherent Laser Corp, Palo Alto, Calif) alone or followed by an erbium:YAG laser (Derma-20, ESC Sharplan, Inc, Needham, Mass) and/or a blended CO(2)/Er:YAG laser (Derma-K, ESC Sharplan) or a variable pulse erbium:YAG laser (Contour, Sciton Laser Corp, Palo Alto). Twenty-one patients were randomly assigned to a postoperative regimen including Silon-TSR (Bio Med Sciences, Inc, Allentown, Pa) for the first 2 to 3 days after laser resurfacing, followed by Aquaphor ointment (Beiersdorf, Charlotte, NC) to complete the first 2 weeks. The other 21 patients received the resurfacing recovery system (RRS, Neutrogena, Los Angeles, Calif) following a specific regimen. The system includes Fibracol wound dressing (Johnson & Johnson, Skillman, NJ) for 2 days, followed by a hydrogel dressing for 1 to 2 days, followed by an ointment to complete the first 2 weeks. Patients were evaluated for wound healing on days 2, 3, 6-10, 14-16, and 28-30. The skin was swabbed for colonization at every visit to determine the quantity of bacteria throughout the healing process. RESULTS: Ninety percent of patients in both groups experienced either "no pain" or "minimal pain" during the first 3 days. Total bacterial counts peaked on days 3 and 6 in the patients managed with the RRS and the Silon-TSR/Aquaphor regimen, respectively. The average day at which patients did not require a dressing was 3.0 days in the group managed with the RRS and 3.7 days in the group managed with the Silon-TSR/Aquaphor dressing regimen (P < or =.05). The average day of complete epithelial regeneration was significantly shorter at 6.3 days using the RRS compared with 7.4 days for patients using the Silon-TSR/Aquaphor regimen (P < or =.02). There was no difference in infection, adverse sequelae, exudate management, or pain in either group. CONCLUSION: Healing was optimized in patients using the RRS after laser resurfacing.