Combined 633-nm and 830-nm led treatment of photoaging skin.

OBJECTIVES: To evaluate the clinical efficacy and ultrastructural changes in photodamaged skin after combined 633-nm and 830-nm light-emitting diode (LED) treatments. METHODS: Thirty-six subjects received 9 LED treatments over the course of 5 weeks and were subsequently evaluated for final clinical improvement 12 weeks after treatment. Five subjects were also biopsied to determine the ultrastuctural posttreatment changes in collagen fibers. RESULTS: A statistically significant improvement in wrinkles was seen after profilometric analysis. The majority of subjects reported improvements in softness, smoothness, and firmness at all time points. Electron microscopic analysis showed evidence of post-LED treatment of thicker collagen fibers. CONCLUSIONS: 633-nm and 830-nm LED treatments play a role in the treatment of photodamaged skin. LED treatments can be used as either a primary or adjunctive treatment modality.

Pharmacokinetics of an implanted osmotic pump delivering sufentanil for the treatment of chronic pain.

BACKGROUND: A matchstick-sized implanted osmotic pump (Chronogesic) that delivers sufentanil subcutaneously for more than 90 days is being developed to treat chronic pain. This study evaluates pharmacokinetic characteristics related to the absorption of sufentanil using a prototype 60-day system. METHODS: Twelve opioid-naive volunteers were given naltrexone to prevent opioid effects. Sufentanil, 60 microg, was infused intravenously over 6 h, then 48 h later, the pump was implanted subcutaneously in the upper arm under local anesthesia. Pumps were removed 9 days later. In six volunteers, fever (1.6-3.3 degrees C) was induced with interleukin-2. Plasma was sampled and population pharmacokinetic modeling was performed to estimate in vivo release rate and absorption half-life. Bioavailability was calculated by comparing in vivo to in vitro release rates. The impact of perturbations in release rate on sufentanil plasma concentration (Cp) was simulated. RESULTS: Fever had no systematic effect on Cp. Release rate estimated in vivo was similar to that measured in vitro; bioavailability did not differ from 100%. Absorption half-life was 16.2 h. Simulation demonstrated that supplemental release of sufentanil from the implant (as might occur with local heating) increases Cp an average of 2.5-2.8% per hours supplemental dose. CONCLUSIONS: An implantable osmotic pump delivered sufentanil in vivo at the rate predicted from in vitro experiments. The rate at which sufentanil was absorbed from the subcutaneous space (half-life > 16 h) was markedly slower than reported with subcutaneous or intramuscular administration of large volumes of dilute opioids; this slow absorption dampens potential changes in Cp if release rate is perturbed.

The central nervous system and cardiovascular effects of levobupivacaine and ropivacaine in healthy volunteers.

UNLABELLED: We compared the central nervous system (CNS) and cardiovascular effects of levobupivacaine and ropivacaine when given IV to healthy male volunteers (n = 14) in a double-blinded, randomized, crossover trial. Subjects received levobupivacaine 0.5% or ropivacaine 0.5% after a test infusion with lidocaine to become familiar with the early signs of CNS effects (e.g., tinnitus, circumoral paresthesia, hypesthesia). The development of CNS symptoms was assessed at 1-min intervals and study drug administration was terminated when the first CNS symptoms were recognized. Thereafter, symptoms were recorded at 1-min intervals until symptom resolution. Hemodynamic variables were assessed by transthoracic electrical bioimpedance. Continuous 12-lead electrocardiogram monitoring was also performed. There was no significant difference between levobupivacaine and ropivacaine for: the mean time to the first onset of CNS symptoms (P = 0.870), mean total volume of study drug administered at the onset of the first CNS symptom (P = 0.595), stroke index (P = 0.678), cardiac index (P = 0.488), acceleration index (P = 0.697), PR interval (P = 0.213), QRS duration (P = 0.637), QT interval (P = 0.724), QTc interval (P = 0.737), and heart rate (P = 0.267). Overall, fewer CNS symptoms were reported for levobupivacaine than ropivacaine (218 versus 277). This study found that levobupivacaine and ropivacaine produce similar CNS and cardiovascular effects when infused IV at equal concentrations, milligram doses, and infusion rates. IMPLICATIONS: This study compared directly, for the first time, the toxicity of levobupivacaine and ropivacaine in healthy volunteers. Levobupivacaine and ropivacaine produced similar central nervous system and cardiovascular effects when infused IV at equal concentrations, milligram doses, and infusion rates.

The effect of nateglinide taken with food on gastric emptying rates in healthy subjects.

OBJECTIVES: The aim of this study was to determine the effect of the timing of food intake on the pharmacokinetics and pharmacodynamics of oral nateglinide 60 mg and the effect of nateglinide on the rate of gastric emptying. METHODS: A randomized, double-blind, placebo-controlled, single-dose, 6-period, crossover study conducted in healthy male volunteers aged 18 to 50 years. On 5 occasions, subjects received a single 60-mg tablet of nateglinide at -30, -10, -5, -1, or 40 minutes from the start of a standard metal. Treatment blind was maintained by administration of placebo tablets at all other time points. On the sixth occasion, subjects received placebo tablets at all dosing time points. Each subject received acetaminophen 1 g at the beginning of the standard breakfast on each treatment day as an indicator of the rate of gastric emptying. Plasma samples were collected over a 6-hour period to determine nateglinide, glucose, insulin, and acetaminophen concentrations. RESULTS: Twelve white men with a mean (SD) age of 30 (6.8) years (range, 21-47 years) and mean (SD) weight of 73.3 (11.0) kg completed all 6 periods of the study. Nateglinide absorption was faster when administered at -5 or -10 minutes relative to food, as characterized by higher nateglinide area under the concentration-time curve from 0 to 5 hours (AUC(0-5)) and maximum plasma concentration (C(max)) values, compared with those observed at other dosing time points. Mean time to C(max) (T(max)) was also shorter when nateglinide was given at -10 minutes versus other dosing time points. Mean nateglinide half-life was similar for all 5 treatments (range, 81.3-94.6 minutes). The overall treatment effect was statistically significant for nateglinide AUC(0-5) (P = 0.031), C(max) (P = 0.001), and T(max) (P < 0.001). Insulin T(max) was shorter after nateglinide administration at -30 or -10 minutes, which was associated with lower glucose C(max) values (-30 minutes, P < 0.05) and a tendency for lower glucose AUC(0-5) values (-10 minutes, P = NS). NS). No treatment effects were observed for any of the acetaminophen indices, as demonstrated by the absence of any change in acetaminophen T(max) or C(max) value. CONCLUSIONS: Nateglinide was well tolerated and no treatment-limiting adverse events were reported in the population studied. Nateglinide administration appeared to have no effect on the rate of gastric emptying as indicated by acetaminophen indices, regardless of the time of nateglinide administration. The findings imply that the time for nateglinide administration to obtain optimal pharmacodynamic effects is prior to food consumption.