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Rapid Dose Escalation (rapid + dose_escalation)

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Medical Sciences100%

Selected Abstracts

Safety, tolerability and efficacy of a rapid dose escalation of quetiapine in bipolar I mania: the FATIMA study

ACTA NEUROPSYCHIATRICA, Issue 3 2009
Eric Constant
Objective: The FATIMA study (FAst TItration of quetiapine fumarate in bipolar I MAnia) evaluated the safety, tolerability and efficacy of a rapid dose escalation of quetiapine in acutely ill bipolar I patients experiencing a manic episode. Methods: In an open-label, phase II pilot study, 29 patients aged 18 years or older, hospitalised with a bipolar I manic episode, received quetiapine twice daily for 21 days. Quetiapine was administered at 200, 400, 600, then 800 mg/day on the first 4 days, with flexible dosing (400,800 mg/day) subsequently. The primary endpoint was the proportion of patient dropouts because of adverse drug reactions during the first 7 days. Secondary safety assessments included incidences of adverse drug reactions and significant changes in vital signs. Efficacy assessments included Young Mania Rating Scale (YMRS) and Clinical Global Impressions Severity of Illness (CGI-S) score changes from day 1 to day 21. Results: Twenty patients (69%) completed the study. No patients withdrew as a result of drug-related adverse events (AEs) during the first 7 days. Twenty-three patients reported 58 adverse events, and most of the adverse events were mild or moderate. No clinically relevant abnormalities in vital signs were reported. Mean YMRS and CGI-S scores decreased significantly from baseline to day 21 (p < 0.001). Response and remission rates were 78 and 70%, respectively, at the end of the study. Conclusion: Rapid dose escalation of quetiapine to 800 mg/day over 4 days was well tolerated and effective in reducing symptoms within 5 days in acutely ill bipolar I patients with a manic episode. [source]

Pharmacokinetics of oral methotrexate in patients with rheumatoid arthritis,

ARTHRITIS & RHEUMATISM, Issue 11 2008
Judith M. Dalrymple
Objective There is evidence supporting a therapeutic range for methotrexate polyglutamate (MTXGlu) concentrations in the treatment of rheumatoid arthritis (RA). Knowledge of the pharmacokinetics of MTXGlu1,5 is required for optimal timing of blood sampling. The aim of this study was to determine the time to steady state and the half-life of accumulation of red blood cell (RBC) MTXGlu1,5 in patients with RA commencing oral MTX, and the time for RBC MTXGlu1,5 to become undetectable and the half-life of elimination of RBC MTXGlu1,5 in patients ceasing treatment with oral MTX. Methods Ten patients beginning treatment and 10 patients stopping treatment with low-dose oral MTX were recruited. Blood samples were initially collected weekly, with gradual extension to monthly collection over the study period. RBC MTXGlu1,5 concentrations were assayed by high-performance liquid chromatography. Results were analyzed using a first-order exponential method. Results The median times to reach steady state in RBCs (defined as 90% of the maximum concentration) were 6.2, 10.6, 41.2, 149, and 139.8 weeks, respectively, for MTXGlu1, MTXGlu2, MTXGlu3, MTXGlu4, and MTXGlu5. The median half-life of accumulation for RBC MTXGlu1,5 ranged from 1.9 weeks to 45.2 weeks. The median times for MTXGlus to become undetectable in RBCs were 4.5, 5.5, 10, 6, and 4 weeks, respectively, for MTXGlu1, MTXGlu2, MTXGlu3, MTXGlu4, and MTXGlu5. The median half-life of elimination for RBC MTXGlu1,5 ranged from 1.2 weeks to 4.3 weeks. Conclusion There is wide interpatient variability of RBC MTXGlu1,5 accumulation and elimination in adults with RA. These data also suggest that after a dose change, >6 months are required for RBC MTXGlu1,5 to reach steady state. Such delays in achieving steady state suggest that more rapid dose escalation or subcutaneous administration from the outset should be considered. [source]

Safety, tolerability and efficacy of a rapid dose escalation of quetiapine in bipolar I mania: the FATIMA study

ACTA NEUROPSYCHIATRICA, Issue 3 2009
Eric Constant
Objective: The FATIMA study (FAst TItration of quetiapine fumarate in bipolar I MAnia) evaluated the safety, tolerability and efficacy of a rapid dose escalation of quetiapine in acutely ill bipolar I patients experiencing a manic episode. Methods: In an open-label, phase II pilot study, 29 patients aged 18 years or older, hospitalised with a bipolar I manic episode, received quetiapine twice daily for 21 days. Quetiapine was administered at 200, 400, 600, then 800 mg/day on the first 4 days, with flexible dosing (400,800 mg/day) subsequently. The primary endpoint was the proportion of patient dropouts because of adverse drug reactions during the first 7 days. Secondary safety assessments included incidences of adverse drug reactions and significant changes in vital signs. Efficacy assessments included Young Mania Rating Scale (YMRS) and Clinical Global Impressions Severity of Illness (CGI-S) score changes from day 1 to day 21. Results: Twenty patients (69%) completed the study. No patients withdrew as a result of drug-related adverse events (AEs) during the first 7 days. Twenty-three patients reported 58 adverse events, and most of the adverse events were mild or moderate. No clinically relevant abnormalities in vital signs were reported. Mean YMRS and CGI-S scores decreased significantly from baseline to day 21 (p < 0.001). Response and remission rates were 78 and 70%, respectively, at the end of the study. Conclusion: Rapid dose escalation of quetiapine to 800 mg/day over 4 days was well tolerated and effective in reducing symptoms within 5 days in acutely ill bipolar I patients with a manic episode. [source]