1. After hydrolysis with glusulase of bile from rats treated with papaverine, four metabolites (A, B, C and D) were separated. 2. The structures A, B and C were established as monodemethylated compounds, 4'-desmethyl-, 7-desmethyl-, and 6-desmethylpapaverine, respectively. 3. D was formed from papaverine by bis-desmethylation. Since it was found in cat bile after administering either A or C, but not B, it was identified as 4', 6-desmethylpapaverine.

Concentrations of antipyrine, phenylbutazone and phenytoin were measured in serum and in tissues of rabbits with acute renal failure after uranyl nitrate injection, in view of our earlier finding that the volume of distribution of phenytoin and of phenylbutazone is increased in those animals. Concentrations of antipyrine in serum and in tissues were not altered in the uraemic rabbit. For phenylbutazone, total serum concentrations were decreased in uraemic rabbits; concentrations in brain, liver and fat were increased, while concentrations in other tissues and unbound serum concentrations were not significantly changed. For phenytoin, total serum concentrations were decreased and unbound serum concentrations and tissue concentrations were not significantly changed in uraemic rabbits. Calculation of the ratios of tissue concentrations over unbound serum concentrations suggests that the increased distribution volume of phenylbutazone and phenytoin in the uraemic rabbit is due to the decreased serum binding rather than to changes in tissue binding.

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BackgroundIntermittent claudication (IC) is pain caused by chronic occlusive arterial disease, that develops in a limb during exercise and is relieved with rest. Buflomedil is a vasoactive agent used to treat peripheral vascular disease. However, its clinical efficacy for IC has not yet been critically examined. This is an update of a Cochrane review first published in 2000, and previously updated in 2007 and 2008. ObjectivesTo evaluate the available evidence on the efficacy of buflomedil for IC. Search methodsFor this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched January 2013) and CENTRAL (2012, Issue 12). Selection criteriaDouble-blinded, randomized controlled trials (RCTs) in patients with IC (Fontaine stage II) receiving oral buflomedil compared with placebo. Pain-free walking distance (PFWD) and maximum walking distance (MWD) were analysed by standardized exercise test. Data collection and analysisTwo authors independently assessed trial quality and extracted data. We contacted study authors for additional information. Main resultsWe included two RCTs with 127 participants. Both RCTs showed moderate improvements in PFWD for patients on buflomedil. This improvement was statistically significant for both trials (WMD 75.1 m, 95% confidence interval (CI) 20.6 to 129.6; WMD 80.6 m, 95% CI 3.0 to 158.2), the latter being a wholly diabetic population. For both RCTs, MWD gains were statistically significant with wide confidence intervals (WMD 80.7 m, 95% CI 9.4 to 152; WMD 171.4 m, 95% CI 51.3 to 291.5), respectively. Authors' conclusionsThere is little evidence available to evaluate the efficacy of buflomedil for IC. Most trials were excluded due to poor quality. The two included trials showed moderately positive results; these are undermined by publication bias since we know of at least another four unpublished, irretrievable, and inconclusive studies.Buflomedil's benefit is small in relation to safety issues and its narrow therapeutic range.

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