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Two-way Crossover Study (two-way + crossover_study)
Selected AbstractsPharmacokinetics and bioavailability of imidocarb dipropionate in swineJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2007D. SU A two-way crossover study was performed in eight healthy young pigs to determine the pharmacokinetics of imidocarb dipropionate (IMDP) following intravenous (2 mg/kg b.w.) and intramuscular (2 mg/kg b.w.) administrations. Each animal received one intravenous and one intramuscular injection with a 30-day washout period between the two-treatments. Plasma concentrations were measured by high-performance liquid chromatography (HPLC) assay with UV detector at regular intervals for up to 24 h post-injection. Intravenous plasma concentration profiles best fit a three-compartmental model yielding a mean system clearance (Cl(s)) of 558 mL/kg·h and a mean half-life of 13.91 h. Mean imidocarb AUC(0,,) (,g·h/mL), Vc (L/kg), Vd(area)(L/kg) and MRT(0-t) (h) values were 3.58, 0.11, 14.36 and 1.46, respectively. Compartmental modeling of imidocarb, after intramuscular administration produced best fit for two-compartmental model yielding mean K, (h,1), Cmax (,g/mL), tmax (h), and bioavailability (%) of 3.89, 2.02, 0.54, and 86.57 for the 2 mg/kg dose level. The present studies showed that IMDP was rapidly absorbed, widely distributed, and slowly eliminated. No adverse effects were observed in any of the pigs after i.v. and i.m. administrations of IMDP. The favorable PK behavior, such as the long half-life, acceptable bioavailability indicated that it is likely to be effective in pigs. [source] Absence of clinically relevant drug interactions following simultaneous administration of didanosine-encapsulated, enteric-coated bead formulation with either itraconazole or fluconazoleBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 2 2002B. Damle Abstract This open-label, two-way crossover study was undertaken to determine whether the enteric formulation of didanosine influences the pharmacokinetics of itraconazole or fluconazole, two agents frequently used to treat fungal infections that occur with HIV infection, and whose bioavailability may be influenced by changes in gastric pH. Healthy subjects were randomized to Treatment A (200-mg itraconazole or 200-mg fluconazole) or Treatment B (same dose of itraconazole or fluconazole with 400 mg of didanosine as an encapsulated, enteric-coated bead formulation). In the itraconazole study, a lack of interaction was concluded if the 90% confidence interval (CI) of the ratio of the geometric means of log-transformed Cmax and AUC0,T values of itraconazole and hydroxyitraconazole, the active metabolite of itraconazole, were contained entirely between 0.75 and 1.33. In the fluconazole study, the equivalence interval for Cmax and AUC0,T was 0.80,1.25. The data showed that for itraconazole the point estimate and 90% CI of the ratios of Cmax and AUC0,T values were 0.98 (0.79, 1.20) and 0.88 (0.71, 1.09), respectively; for hydroxyitraconazole the respective values were 0.91 (0.76, 1.08) and 0.85 (0.68, 1.06). In the fluconazole study, the point estimate and 90% CI of the ratios of Cmax and AUC0,T values were 0.98 (0.93, 1.03) and 1.01 (0.99, 1.03), respectively. The Tmax for itraconazole, hydroxyitraconazole, and fluconazole were similar between treatments. Both studies indicated a lack of clinically significant interactions of the didanosine formulation with itraconazole or fluconazole. These results showed that the encapsulated, enteric-coated bead formulation of didanosine can be concomitantly administered with drugs, such as the azole antifungal agents, whose bioavailability may be influenced by interaction with antacids. Copyright © 2002 John Wiley & Sons, Ltd. [source] Effect of systemic moxaverine on ocular blood flow in humansACTA OPHTHALMOLOGICA, Issue 7 2009Hemma Resch Abstract. Purpose:, A number of common eye diseases are associated with ocular perfusion abnormalities. The present study aimed to investigate whether systemically administered moxaverine improves ocular blood flow. Methods:, Sixteen healthy volunteers were studied in this randomized, double-masked, placebo-controlled, two-way crossover study. Moxaverine in a dose of 150 mg was administered i.v. Ocular haemodynamic parameters were measured before and after drug administration. Retinal arterial and venous diameters were measured with a retinal vessel analyser. Retinal blood velocity was assessed using laser Doppler velocimetry and choroidal and optic nerve head blood flow was measured with laser Doppler flowmetry. Results:, Moxaverine increased choroidal blood flow (22.6 ± 27.9%), an effect which was significant versus placebo (p = 0.015). Red blood cell velocity in retinal veins tended to increase by 13.6 ± 13.3% after infusion of moxaverine, but this effect was not significant compared with placebo (p = 0.25). In the optic nerve head moxaverine also tended to increase blood flow (11.8 ± 12.7%), but, again, this effect was not significant versus placebo (p = 0.12). Neither moxaverine nor placebo had an effect on retinal arterial diameters. In retinal veins moxaverine tended to induce vasodilation (2.6 ± 2.8%) and to increase blood flow (19.6 ± 16.5%), but these effects were not significant (both p = 0.12). Conclusions:, The present study indicates an increase in choroidal blood flow after systemic infusion of a single dose of moxaverine in healthy subjects. Further studies are warranted to investigate whether these effects are also seen after longterm treatment in patients with ocular vascular disease. [source] Influence of Ginkgo biloba on ocular blood flowACTA OPHTHALMOLOGICA, Issue 4 2007Barbara Wimpissinger Abstract. Purpose:, To investigate the effect of Ginkgo biloba extract (EGb761) on ocular blood flow. Methods:, This randomized, double-masked, placebo-controlled, two-way crossover study included 15 healthy male volunteers. Measurements were taken with laser Doppler flowmetry, laser Doppler velocimetry, a retinal vessel analyser, laser interferometry and applanation tonometry, before and up to 3 hours after oral intake of 240 mg EGb761. Results:, At baseline, no significant differences in ocular and systemic haemodynamic parameters were observed between the two study days. Ginkgo biloba significantly decreased retinal venous diameters (p < 0.05 versus baseline), but there was no significant difference between the two groups. Blood pressure, retinal arterial and venous diameters, choroidal blood flow, fundus pulsation amplitude, intraocular pressure and retinal blood flow remained unchanged in both groups and did not differ between groups. Optic nerve head blood flow significantly increased in response to Ginkgo biloba (p < 0.002 versus baseline), but this effect was not significant compared with that of placebo. Conclusions:, The results of this study indicate that a single administration of Ginkgo biloba does not influence ocular blood flow to a relevant degree. Whether the drug may influence ocular blood flow in patients with ocular vascular disease after longterm treatment remains to be investigated in a randomized, placebo-controlled clinical trial. [source] | ||||||||||