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The gastroesophageal reflux and/or peptic ulcer diseases are clinical conditions that occur usually accompanied of symptomatic pain. Lansoprazole, a proton pump inhibitor class drug is widely used in clinical practice for treatment of these diseases. However, its efficacy can be improved by combining with spasmolytic and/or visceral analgesic such as hyoscine butylbromide. Since hyoscine butylbromide is barely absorbed and exerts some local effects at gastrointestinal tract which may modify the absorption of lansoprazole, it is important to establish if there is a pharmacokinetic interaction after the oral concomitant administration of both drugs. For this objective, twenty-five subjects received under a crossover design an oral administration of lansoprazole (15 mg) plus placebo or a fixed-dose combination with hyoscine butiylbromide (15 mg + 10 mg, respectively). Plasma samples were obtained at different times during 10 hours. Lansoprazole plasma concentrations were determined by a high performance liquid chromatography method coupled to tandem mass spectrometry. Fixed-dose combination was well tolerated. Lansoprazole pharmacokinetic parameters were: Cmax 621.81 ± 212.79 and 450.38 ± 192.14 ng/mL; AUC0-t 1941.36 ± 845.57 and 1454.66 ± 757.28 ng·h/mL; tmax 2.83 ± 0.99 and 3.40 ± 1.82h; t1/2 1.35 ± 0.39 and 1.45 ± 0.51 h, for alone and combined fixed-dose formulation, respectively. Pharmacokinetic parameters were compared by analysis of variance and ratios of AUC0-t, Cmax and 90% confidence intervals obtained. Since confidence intervals exceed the 80% - 125% limits for these parameters, we conclude that there is a significantly pharmacokinetic interaction of lansoprazole when it is administered concomitantly with hyoscine butylbromide.

The present study aimed to investigate the possible influence of several inhibitors and blockers on the vascular effect produced by the acute in vitro application of rosuvastatin to phenylephrine-precontracted aortic rings from rats with a semi-solid, cafeteria-style (CAF) diet. It also aimed to examine the effects of rosuvastatin on the expression of endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase, constitutive cyclooxygenase, and inducible cyclooxygenase in aortic rings from rats with a CAF diet. From comparisons of the effect on phenylephrine-precontracted aortic rings extracted from rats with two different diets (a standard and a CAF diet), it was found that 10(-9) -10(-5) -mol/L rosuvastatin produced lower concentration-dependent vasorelaxation on rings from the CAF diet group. The vasorelaxant effect was unaffected by the vehicle, but it was significantly attenuated by 10(-5) -mol/L N(G) -nitro-l-arginine methyl ester, 10(-2) -mol/L tetraethylammonium, 10(-3) -mol/L 4-aminopyridine, 10(-7) -mol/L apamin plus 10(-7) -mol/L charybdotoxin, 10(-5) -mol/L indomethacin, or 10(-5) -mol/L cycloheximide. Moreover, in aortic rings from rats with a CAF diet, rosuvastatin enhanced the expression of eNOS, inducible nitric oxide synthase, constitutive cyclooxygenase, and inducible cyclooxygenase. The acute in vitro application of rosuvastatin to phenylephrine-precontracted aortic rings from rats with a CAF diet had a vasorelaxant effect. Overall, the present results suggest that the stimulation of eNOS, the opening of Ca(2+) -activated and voltage-activated K(+) channels, the stimulation of prostaglandin synthesis and enhanced protein levels of eNOS, inducible nitric oxide synthase, constitutive cyclooxygenase, and inducible cyclooxygenase are involved in this relaxant effect.

A rapid, sensitive and simple high-performance liquid chromatographic assay with ultraviolet detection was developed for the quantification of levofloxacin in microsamples (100 μL) of human plasma. The extraction procedure included a protein precipitation technique and a short chromatographic running time (4.5 min). Analyses were carried out on a Symmetry C18 column using a mixture of acetonitrile and 0.01 m potassium dihydrogen aqueous solution (pH 3.4; 14:86 v/v) as mobile phase. The method provided specificity and was linear (r ≥ 0.9992) over the concentration range 0.1-12 µg/mL. The average absolute recovery was 93.59%. The intra- and inter-day coefficients of variation were

A relationship between thyroid hormones and the cardiovascular system has been well established in the literature. The present in vitro study aimed to investigate the mechanisms involved in the vasodilator effect produced by the acute application of 10-8–10-4 M triiodothyronine (T3) to isolated rat aortic rings. Thoracic aortic rings from 80 adult male Wistar rats were isolated and mounted in tissue chambers filled with Krebs-Henseleit bicarbonate buffer in order to analyze the influence of endothelial tissue, inhibitors and blockers on the vascular effect produced by T3. T3 induced a vasorelaxant response in phenylephrine-precontracted rat aortic rings at higher concentrations (10-4.5–10-4.0 M). This outcome was unaffected by 3.1×10-7 M glibenclamide, 10-3 M 4-aminopyridine (4-AP), 10-5 M indomethacin, or 10-5 M cycloheximide. Contrarily, vasorelaxant responses to T3 were significantly (P

Amfepramone (diethylpropion) is an appetite-suppressant drug used for the treatment of overweight and obesity. It has been suggested that the systemic and central activity of amfepramone produces cardiovascular effects such as transient ischemic attacks and primary pulmonary hypertension. However, it is not known whether amfepramone produces immediate vascular effects when applied in vitro to rat aortic rings and, if so, what mechanisms may be involved. We analyzed the effect of amfepramone on phenylephrine-precontracted rat aortic rings with or without endothelium and the influence of inhibitors or blockers on this effect. Amfepramone produced a concentration-dependent vasorelaxation in phenylephrine-precontracted rat aortic rings that was not affected by the vehicle, atropine, 4-AP, glibenclamide, indomethacin, clotrimazole, or cycloheximide. The vasorelaxant effect of amfepramone was significantly attenuated by NG-nitro-L-arginine methyl ester (L-NAME) and tetraethylammonium (TEA), and was blocked by removal of the vascular endothelium. These results suggest that amfepramone had a direct vasorelaxant effect on phenylephrine-precontracted rat aortic rings, and that inhibition of endothelial nitric oxide synthase and the opening of Ca2+-activated K+ channels were involved in this effect.

Ketoprofen is a nonsteroidal antiinflammatory drug (NSAID) widely used in therapeutics. However, gastrointestinal toxicity may limit its use. To reduce the requirements of NSAIDs and hence their toxicity, these compounds have been combined with several drugs. B vitamins increase the analgesic activity of NSAIDs, but conflicting results have been obtained. The purpose of this study was to establish whether a vitamin B mixture can increase the antinociceptive effect of ketoprofen in the thermal paw stimulation model and in antiinflammatory activity in carrageenan-induced paw edema in the rat. Ketoprofen produced a dose-dependent antinociception, whereas a mixture of B vitamins produced a very limited antinociceptive effect. However, B vitamins were able to increase the antinociceptive effect of ketoprofen, reaching effects similar to those obtained with the maximal dose of ketoprofen tested. Ketoprofen produced a dose-dependent antiinflammatory activity and B vitamins also produced significant antiinflammatory effects. When ketoprofen was combined with a mixture of B vitamins, an increase in the antiinflammatory action was observed. These results indicate that coadministration of B vitamins with ketoprofen can increase both antihyperalgesic and antiinflammatory effects. Thus, B vitamins are effective as analgesic adjuvants in the models tested. Drug Dev. Res. 64:66–70, 2005. © 2005 Wiley-Liss, Inc.

Introduction: Meloxicam is a nonsteroidal anti-inflammatory agent used widely in therapeutics. It is mainly metabolised by the cytochrome P450 enzyme (CYP) 2C9, with minor involvement of CYP3A4. So far, no information on the oral pharmacokinetics of this drug in adult Mexicans is available. The purpose of this study was to evaluate the oral pharmacokinetics of meloxicam in Mexican subjects. Methods: Twenty-four healthy male subjects received an oral dose of meloxicam 7.5mg after fasting for 10 hours. Blood samples were drawn from a suitable forearm vein and plasma obtained. The meloxicam concentration was evaluated by a high-performance liquid Chromatographic method and pharmacokinetic parameters were obtained by non-compartmental techniques. Pharmacokinetic parameters obtained in this study were compared with those reported under similar conditions in other populations in order to establish if interethnic differences in the pharmacokinetics of meloxicam exist. Results: After administration of meloxicam, plasma levels increased to a maximum concentration (Cmax) of 0.702 ± 0.027 (mean ± SEM) μg/mL with a time to reach Cmax of 4.77 ± 0.65h. The area under the plasma concentration versus time curve was 24.82 ± 1.23 μg · h/mL. The clearance was about 4.8 mL/min and the volume of distribution 9.8 ± 0.36L. When these parameters were compared with those reported in German and Indian subjects, a reduced clearance and volume of distribution were evident in Mexicans. However, clearance and volume of distribution obtained in this study were very similar to those reported in Chinese subjects. Conclusions: The oral pharmacokinetic parameters of meloxicam in healthy Mexican subjects compared with historic controls reported in other populations showed a reduced clearance and volume of distribution when compared with German subjects, whereas no differences between Mexican and Chinese subjects were observed. These results suggest that there are interethnic differences in the pharmacokinetics of meloxicam.

The relationship between blood levels of ketoprofen and its anti-hyperalgesic effects was examined in rat using the carrageenan-evoked thermal hyperalgesia model. Female adult Wistar rats were injected with carrageenan into the plantar surface of the right hind paw. Immediately after, rats were administered with ketoprofen po and hindpaw withdrawal latency measured and micro-whole blood samples were obtained over six hours via a cannula inserted in the caudal artery. Ketoprofen levels were measured by HPLC. Ketoprofen concentration increased in a dose-dependent manner and was reflected in dose-dependent anti-hyperalgesic effect. The pharmacokinetic and pharmacodynamic parameters expressed as mean ± s.e.m. following administration of 1, 3.2, and 10 mg/kg ketoprofen were: Cmax 1.27 ± 0.08, 3.44 ± 0.20 and 11.76 ± 0.81 μg/mL; AUClast 4.16 ± 0.17, 11.63 ± 0.65 and 28.15 ± 1.32 μg h/mL; and Emax observed (AUCE ): 65.41 ± 7.79, 92.06 ± 6.46 and 98.42 ± 7.53%. A direct relationship between blood concentrations and the anti-hyperalgesic effect of ketoprofen followed a maximum effect model equation. The results indicate that the anti-hyperalgesic effect of ketoprofen in the carrageenan pain model can be predicted by the pharmacokinetic properties of ketoprofen.