Rinsho yakuri/Japanese Journal of Clinical Pharmacology and Therapeutics

We studied the effect of the combined use of lecithinized superoxide dismutase (PC-SOD) and methylprednisolone (MPSL) on the interstitial pneumonia model induced by bleomycin in mice. PC-SOD, which is made up of 4 lecithin derivative molecules covalently bound to the recombinant human Cu, Zn-SOD dimer, shows a high affinity for cell membranes and a longer plasma half-life. Treatment with PC-SOD at 1 mg/kg plus MPSL at 0.03 mg/kg and PC-SOD at 10 mg/kg plus MPSL at 0.03 mg/kg significantly reduced the hydroxyproline content compared with the control (treatment with 5% xylitol). And treatment with PC-SOD at 1 mg/kg plus MPSL at 0.03 mg/kg significantly reduced the hydroxyproline content compared with treatment with PC-SOD alone at 1 mg/kg. These results demonstrated that the combined use of PC-SOD and MPSL was more effective than use of PC-SOD alone, and it suggested that the 0₂^- scavenging activity of PC-SOD and the anti-inflammatory activity of MPSL cooperatively suppressed the progression of pulmonary fibrosis.

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Background: Ketotifen, an anti-allergic drug with a histamine H₁-receptor antagonistic component, has demonstrated sedative effects upon oral administration. The objective of our study was to investigate whether the topical use of ketotifen via the ocular and/or nasal route produced any sedative effects.
Methods: Twelve healthy young male volunteers received each of the following treatments on four different occasions in a randomized, double-blind, Latin-square, placebo-controlled design: (A) ketotifen eye drops (1 mg) + ketotifen nasal drops (1 mg); (B) ketotifen eye drops+ placebo nasal drops; (C) placebo eye drops+ ketotifen nasal drops ; and (D) placebo eye drops + placebo nasal drops. Before and 1 and 2 hours after each treatment the random number addition test (RNAT), digit symbol substitution test (DSST), critical fusion frequency threshold (CFFT) and the visual analog scale (VAS) for subjective feeling of sedation were measured.
Results: Neither RNAT nor DSST showed significant changes after ocular and/or nasal administration of ketotifen. The co-administration of ketotifen via the ocular and nasal routes significantly reduced CFFT (p<0.05). VAS showed no significant changes in the subjective feeling of sedation.
Conclusion: Topical combined use of ketotifen via the ocular and nasal routes led to an impaired response on CFFT.

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Administration of pravastatin to patients with hypercholesterolemia has been reported to improve peripheral hemodynamics of the systemic circulatory system. Therefore, we studied the target values of treatment to lower total cholesterol (TC) for reliable improvement of hemodynamics. The subjects were 28 patients with hypercholesterolemia (TC≥220 mg/dl) who showed a decrease of TC values of at least 15% when administered pravastatin at a dose of 10 mg/day for 8 to 10 months. These patients were divided into three groups: group A (TC under 200 mg/dl), group B (200-220) and group C (220 or higher) according to the TC values after treatment. Changes in the hemodynamics were compared before and after pravastatin treatment. After treatment with pravastatin, no changes in blood pressure, heart rate and aortic damping factor were observed ; only group A showed decreases in the pulse wave velocity and total peripheral resistance, an increase in cardiac output, shortening of the hemodynamic ICT and PEP, and an increase in ET/PEP. Therefore, the target TC for treatment with pravastatin which can be expected to improve the hemodynamics is considered to be less than 200 mg/dl.

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