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Infusion Schedules (infusion + schedule)
Selected AbstractsShort-term cortisol infusion in the brachial artery, with and without inhibiting 11,-hydroxysteroid dehydrogenase, does not alter forearm vascular resistance in normotensive and hypertensive subjectsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 12 2002S. H. M. Van Uum Abstract Background Vascular tone is increased in primary hypertension, and glucocorticoids affect vascular tone. Local cortisol availability is modulated by activity of 11,-hydroxysteroid dehydrogenase (11,-HSD). As this activity may be decreased in patients with primary hypertension, vascular sensitivity to cortisol may be increased in these patients. We studied the acute effect of cortisol on forearm vascular resistance (FVR) by infusing cortisol directly into the brachial artery, both with and without inhibition of 11,-HSD, in normotensive and hypertensive subjects. Design Twenty normotensive volunteers and 20 patients with primary hypertension participated in the study. After a 10-min infusion of vehicle (glucose 5%), cortisol was infused into the brachial artery in three stepwise increasing doses (3·5, 10·5 and 35 µg per 100 mL of forearm volume), each for 10 min. Next, the participants received placebo or 500 mg glycyrrhetinic acid (GA) orally, and 150 min later the same infusion schedule was repeated. Forearm vascular resistance was measured during the last 5 min of the infused vehicle and of each dose. Arterial and forearm venous plasma samples for measurement of cortisol and cortisone were taken at the end of the infusions of glucose 5% and the highest cortisol dose. Results In both normotensive and hypertensive subjects, neither the infusion of cortisol nor the administration of GA changed FVR. Also 2 h after the cortisol infusion there remained no change in FVR in both the normotensive and hypertensive groups who received placebo. Following the infusion of the highest cortisol dose, total plasma cortisone levels in the venous plasma were decreased compared with levels in the arterial plasma (36 ± 3 and 49 ± 4 nmol L,1, respectively, P < 0·05). The protein-bound venous cortisone was 37·1 ± 4·8 nmol L,1 during the vehicle compared with 23·9 ± 3·7 nmol L,1 during the cortisol infusion (P < 0·01), whereas the free cortisone level was not altered by the cortisol infusion. Conclusions In both normotensive and hypertensive subjects, high-dose cortisol infusion both with and without 11,-HSD inhibition did not change FVR either immediately or after 2 h. We could not demonstrate in vivo 11,-HSD activity in the forearm vascular tissues. When binding of cortisone to CBG is changed, e.g. during cortisol infusion, arterio-venous changes in cortisone cannot reliably be used to assess (alterations in) local 11,-HSD activity. [source] Rapid infusion of rituximab with or without steroid-containing chemotherapy: 1-yr experience in a single institutionEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 4 2006Antonio Salar Abstract:, We assessed the feasibility of a rapid infusion of rituximab with or without steroid-containing chemotherapy. Inclusion criteria: previous infusion of rituximab without grade 3 or 4 toxicity, lymphoid cells <5 × 109/L and rituximab dose of 375 mg/m2. Seventy patients were treated with a total of 319 rapid rituximab infusions [126 (40%) with and 193 (60%) without steroids]. Overall, rapid infusion of rituximab was well tolerated , there were no grade 3 or 4 adverse events. Only, three patients developed symptoms, all grade 1. In conclusion, rituximab administration in a 90-min infusion schedule is well tolerated and safe, both in patients who are administered steroids and in patients who are not. [source] The Effect of Different Dosing Schedules of UCN-01 on its Pharmacokinetics and Cardiohaemodynamics in DogsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 11 2000N. KURATA 7-Hydroxy-staurosporine (UCN-01) is now under development as a novel anticancer drug. In clinical studies, different infusion schedules are being investigated in the USA and Japan. To examine the effect of different infusion schedules on the pharmacokinetics and cardiohaemodynamics of UCN-01, dogs were treated with UCN-01 as either a 3-h or a 24-h constant intravenous infusion. Blood pressure and heart rate, together with UCN-01 concentrations during and after infusion, were monitored. To analyse the relationship between the pharmacokinetics and cardiohaemodynamics of UCN-01, the plasma concentration of UCN-01 at the end of infusion (Cend), the area under the plasma concentration versus time curves (AUC0-,) and the mean residence time (MRT) were used. As indices of cardiohaemodynamic changes, the area under decreasing systolic blood pressure and increasing heart rate versus time curves (dAUCpressure and AUCheart rate) were calculated by the trapezoidal method. For the 3-h (0.22 and 0.65 mgkg,1) and 24-h infusion (0.81 to 6.48 mgkg,1), systolic and diastolic blood pressures fell after or during infusions, accompanied by a dose-dependent increase in heart rate for both infusions. During both infusion schedules, the plasma concentrations of UCN-01 gradually increased and Cend showed a dose-proportional increase. After that, UCN-01 was eliminated bi-exponentially with an elimination half-life of 5.14 ± 1.12 to 8.32 ± 1.80 h. The total clearance (CLtotal) ranged from 0.383 to 0.666 ± 0.149L h,1kg,1. There was no significant difference in these parameters among the doses in each infusion schedule, indicating that UCN-01 has a linear pharmacokinetic profile over the dose range examined for each infusion, and there were also no significant differences between the 3-h and 24-h infusion except for MRT. The pharmacokinetic parameters of Cend, AUC0-, and slope0-3h exhibited a degree of correlation with the AUCheart rate in the 3-h infusion and correlated significantly with the dAUCpressure in the 24-h infusion. The MRT did not correlate with cardiohaemodynamic changes during either infusion. In conclusion, the pharmacokinetic profile of UCN-01 after the shorter infusion is similar to that after the longer one. However, a longer dosing period of UCN-01 increased the residence time in comparison with the shorter infusion. This may be due to the effect on the circulatory function in dogs. [source] A randomized phase 2 trial comparing 3-hour versus 96-hour infusion schedules of paclitaxel for the treatment of metastatic breast cancerCANCER, Issue 4 2010MSCI, Stacy L. Moulder MD Abstract BACKGROUND: This study was performed to compare efficacy and toxicity profiles of paclitaxel using 3-hour versus 96-hour infusion schedules. METHODS: Patients with metastatic breast cancer (MBC) were randomly assigned to receive paclitaxel starting at a dose of 250 mg/m2 intravenously (iv) over 3 hours every 21 days or paclitaxel starting at a dose of 140 mg/m2 iv over 96 hours every 21 days. Stratification variables included number of prior chemotherapy regimens and previous response to anthracyclines. Response was assessed every 2 cycles using bidimensional measurements. Patients were allowed to cross over at disease progression or therapy intolerance. RESULTS: A total of 214 patients received therapy (107 patients per arm). Response rates were similar: 23.4% in the 3-hour arm and 29.9% in the 96-hour arm (P = .28). The median duration of response (8.9 months vs 5.7 months; P = .75) and progression-free survival (5.0 months vs 3.8 months; P = .17) slightly favored the 96-hour arm. Overall survival was slightly longer in the 3-hour arm (14.2 months vs 12.7 months; P = .57). One patient who crossed over to the 96-hour arm (N = 18) developed a partial response; no response was noted with crossover to the 3-hour arm (N = 10). Myalgia/arthralgia and neuropathy were more frequent in the 3-hour arm, whereas mucositis, neutropenic fever/infection, and diarrhea were more common in the 96-hour arm. CONCLUSIONS: Paclitaxel given by 3-hour or 96-hour infusion was active in MBC. The 96-hour paclitaxel regimen did not significantly improve response or time to disease progression, was more cumbersome to administer, and was associated with greater myelosuppression (but less neuropathy and myalgia) compared with the 3-hour schedule. Cancer 2010. © 2010 American Cancer Society. [source] | ||||||||||