The transdermal absorption of a series of nonsteroidal antiinflammatory drugs (NSAIDs): indomethacin, ketoprofen, diclofenac, piroxicam, tenoxicam, ketorolac, and aceclofenac) was studied in vitro with human skin. The purpose of the study was to determine the permeation parameters (permeability rate constant, Kp; lag time, TL, and flux, J) as measures of the intrinsic transdermal permeabilities of these drugs to predict their potential for formulation in a transdermal therapeutic system (TTS). A linear correlation was established between the intrinsic log Kp values and the intrinsic partition coefficients (r = 0.863, p = 0.012, n = 7). Diclofenac had the highest value of in vitro transdermal penetration at approximately 0% ionization (Kp = 3.5 cm/h) and ketoprofen had the highest flux (J = 16 micrograms/h.cm2) of the NSAIDs assayed. Ketorolac would provide the plasma concentrations at steady state that would be nearest to the therapeutic concentration (Cr/Css = 26). Also, considering the whole permeation profile in vitro, ketorolac would be the most suitable candidate of the series studied to be formulated as a TTS.

Introduction: Lipemic specimens are a common and frequent, but yet unresolved problem in clinical chemistry, and may produce signifi cant interferences in the analytical results of diff erent biochemical parameters. Material and methods:The aim of this study was to examine the eff ect of lipid removal using ultracentrifugation of lipemic samples, on some routine biochemistry parameters. Among all the samples obtained daily in our laboratory, the ones which were visibly muddy were selected and underwent to a process of ultracentrifugation, being determined a variety of biochemical tests before and after ultracentrifugation. A total of 110 samples were studied. Results: We found signifi cant diff erences in all the parameters studied except for total bilirubin, glucose, gamma-glutamyl transferase (GGT) and aspartate aminotransferase (AST). The greatest diff erences in the parameters analyzed were found in the concentration of alanine aminotransferase (ALT) (7.36%) and the smallest ones in the concentration of glucose (0.014%). Clinically signifi cant interferences were found for phosphorus, creatinine, total protein and calcium. Conclusion: Lipemia causes clinically signifi cant interferences for phosphorus, creatinine, total protein and calcium measurement and those interferences could be eff ectively removed by ultracentrifugation.

The pharmacokinetics/tolerability of lanreotide Autogel have been evaluated. Healthy volunteers (n = 24) first received immediate-release lanreotide as a single subcutaneous (s.c.) injection. After two days, 40 or 60 mg lanreotide Autogel was injected subcutaneously. Blood was sampled at various intervals for 56 days. Systemic/local adverse events and changes in biological profile/vital signs were recorded. Lanreotide Autogel produced a prolonged-release pharmacokinetic profile: mean area under the serum concentration-time curve from time 0 to infinity (AUC) was 53.73 +/- 8.99 and 79.48 +/- 13.06 ng mL(-1) day for 40 and 60 mg, respectively, mean peak serum concentration (C(max)) was 4.38 +/- 2.91 and 5.71 +/- 3.52 ng mL(-1), respectively, median time to reach C (minimum-maximum) was 0.50 (0.083-18.0) and 0.38 (0.083-9.01) days, respectively, mean apparent elimination half-life was 21.63 +/- 9.42 and 22.01 +/- 9.87 days, respectively, and relative bioavailability was 0.93 +/- 0.12 and 0.82 +/- 0.15, respectively. Thus, lanreotide Autogel exhibited linear pharmacokinetics for the doses studied. Pharmacokinetic profiles were similar in both genders, apart from statistically significant differences in C(max) and C(max)/AUC. The Autogel formulation of lanreotide was well tolerated, with systemic adverse events being mild/moderate. Erythema and a painless subcutaneous induration were the most common local adverse events. Lanreotide Autogel provided a prolonged dosing interval and good tolerability for treating acromegaly and carcinoid syndrome.

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Anti-vascular endothelial growth factor for proliferative diabetic retinopathy.