Comparison of Plasma Concentrations for Two Amiodarone Products

2002 ◽  
Vol 36 (11) ◽  
pp. 1682-1685 ◽  
Author(s):  
Shari C Sauro ◽  
Douglas D DeCarolis ◽  
Gordon L Pierpont ◽  
Charles C Gornick
Keyword(s):  
Steady State ◽  
Medical Center ◽  
Plasma Concentrations ◽  
Veterans Affairs ◽  
Brand Name ◽  
Drug Concentrations ◽  
Pharmacokinetic Properties ◽  
Before And After ◽  
The Mean ◽  
State Plasma

BACKGROUND: A generic formulation of amiodarone was recently approved by the Food and Drug Administration based on single-dose equivalence data. Because amiodarone has complex pharmacokinetic properties, a narrow therapeutic range, and a significant adverse effect profile, concern about equivalency persists. OBJECTIVE: To compare steady-state plasma concentrations of the brand-name reference product Cordarone with the AB-rated generic formulation, Pacerone, in patients exposed to both products. METHODS: A retrospective analysis was performed at the Minneapolis Veterans Affairs Medical Center on 138 patients who were taking a stable dose of amiodarone before and after an amiodarone generic product substitution. RESULTS: Seventy-seven patients had steady-state plasma concentrations documented for each product at the same dose. The mean steady-state plasma concentrations of amiodarone were not significantly different for Cordarone compared with Pacerone (1.07 ± 0.48 vs. 1.19 ± 0.66 μg/mL, respectively); similarly, the concentrations of the active metabolite (desethylamiodarone) did not differ (0.95 ± 0.30 vs. 0.96 ± 0.49 μg/mL, respectively). However, the variability in plasma drug concentrations between products was increased as compared to variability within each product. CONCLUSIONS: This study indicates that comparable steady-state concentrations can be achieved with a change in formulation from Cordarone to Pacerone. However, individual responses vary, suggesting that monitoring of plasma concentrations is prudent 1–3 months after any change from one product to another.

scholarly journals Comparison of Plasma, Epithelial Lining Fluid, and Alveolar Macrophage Concentrations of Solithromycin (CEM-101) in Healthy Adult Subjects

2012 ◽  
Vol 56 (10) ◽  
pp. 5076-5081 ◽  
Author(s):  
Keith A. Rodvold ◽  
Mark H. Gotfried ◽  
J. Gordon Still ◽  
Kay Clark ◽  
Prabhavathi Fernandes
Keyword(s):  
Steady State ◽  
High Performance ◽  
Healthy Adult ◽  
Plasma Concentrations ◽  
Epithelial Lining ◽  
Time Curve ◽  
Epithelial Lining Fluid ◽  
Once Daily ◽  
Drug Concentrations ◽  
The Mean

ABSTRACTThe steady-state concentrations of solithromycin in plasma were compared with concomitant concentrations in epithelial lining fluid (ELF) and alveolar macrophages (AM) obtained from intrapulmonary samples during bronchoscopy and bronchoalveolar lavage (BAL) in 30 healthy adult subjects. Subjects received oral solithromycin at 400 mg once daily for five consecutive days. Bronchoscopy and BAL were carried out once in each subject at either 3, 6, 9, 12, or 24 h after the last administered dose of solithromycin. Drug concentrations in plasma, ELF, and AM were assayed by a high-performance liquid chromatography-tandem mass spectrometry method. Solithromycin was concentrated extensively in ELF (range of mean [± standard deviation] concentrations, 1.02 ± 0.83 to 7.58 ± 6.69 mg/liter) and AM (25.9 ± 20.3 to 101.7 ± 52.6 mg/liter) in comparison with simultaneous plasma concentrations (0.086 ± 0.070 to 0.730 ± 0.692 mg/liter). The values for the area under the concentration-time curve from 0 to 24 h (AUC0–24values) based on mean and median ELF concentrations were 80.3 and 63.2 mg · h/liter, respectively. The ratio of ELF to plasma concentrations based on the mean and median AUC0–24values were 10.3 and 10.0, respectively. The AUC0–24values based on mean and median concentrations in AM were 1,498 and 1,282 mg · h/L, respectively. The ratio of AM to plasma concentrations based on the mean and median AUC0–24values were 193 and 202, respectively. Once-daily oral dosing of solithromycin at 400 mg produced steady-state concentrations that were significantly (P< 0.05) higher in ELF (2.4 to 28.6 times) and AM (44 to 515 times) than simultaneous plasma concentrations throughout the 24-h period after 5 days of solithromycin administration.

scholarly journals Quality of life of obstetrics fistula patients before and after surgical repair in the Jimma University Medical Center, Southwest Ethiopia

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Tilahun Fufa Debela ◽  
Zerihun Asefa Hordofa ◽  
Aster Berhe Aregawi ◽  
Demisew Amenu Sori
Keyword(s):  
Quality Of Life ◽  
Surgical Repair ◽  
Obstetric Fistula ◽  
Medical Center ◽  
Mean Value ◽  
Significant Difference ◽  
Before And After ◽  
The Mean ◽  
Jimma University

Abstract Background The consequences of obstetric fistula on affected women are more than the medical condition. It has extensive physical, psychological, social, and economic consequences on them. Obstetric fistula affects the entire health and entire life of women. Women suffering from obstetric fistula are often abandoned by her partner, relatives, and the community. This study aimed to determine the quality of life of obstetrics fistula patients before and after surgical repair. Methods Institutional-based prospective, before and after study design was conducted in the Jimma University Medical Center from November 1, 2019–October 30, 2020. A face-to-face interview was conducted with fistula patients who visited Jimma University Medical center, fistula clinic during the study period. All fistula patients were included in the study. Accordingly, 78 women who underwent surgical repair were interviewed. The means and the standard deviation were computed using conventional statistics formulas. The unpaired t-test was used to compare two independent means, and one-way analysis of variance (ANOVA) was used to compare the quality of life before repair and after a successful repair. Linear regression analysis was done for identifying determinants of quality of life. A P value of 0.05 will be considered statistical significance. Result The overall quality of life of women was 58.17 ± 7.2 before the surgical repair and 71.20 ± 10.79 after surgical repair. The result indicates there is a significant difference in the mean value of pre and post-operative (P < 0.001). The overall satisfaction of women with their health status before the surgical repair was 22.5 ± 1.30and it has increased to 53.0 ± .90after surgical repair. The physical health dimension score was 16.51 ± 5.27 before the surgical repair while it has increased to 21.77 ± 5.38 after the surgical repair. The score of the social domain before the surgical repair was 5.19 ± 1.34 and it has increased to 7.13 ± 3.67 after the surgical repair. The score of the environmental health domain was 17.41 ± 2.89 before the surgery while it also increased to 21.65 ± 4.04 after the surgical repair. The results have shown there was a significant difference in the mean values of pre and post-operatives in both social and environmental scores (P < 0.001). The score of the psychological health domain before the surgery was 19.06 ± 1.46 and it was increased to 19.84 ± 3.21 after the surgical repair. The result showed there is a significant difference in mean value pre and post-operative (P = 0.048), though it is a slight improvement compared to other domains. Conclusion The overall quality of life of the patient with fistula was improved after successful surgical repair. Although all domains of quality of life had shown significant improvement after successful surgical repair, the psychological domain showed slight improvement.

scholarly journals Fasting Remnant Lipoprotein Cholesterol and Triglyceride Concentrations Are Elevated in Nondiabetic, Insulin-Resistant, Female Volunteers1

1999 ◽  
Vol 84 (11) ◽  
pp. 3903-3906 ◽  
Author(s):  
Fahim Abbasi ◽  
Tracey McLaughlin ◽  
Cindy Lamendola ◽  
Helen Yeni-Komshian ◽  
Akira Tanaka ◽  
...  
Keyword(s):  
Steady State ◽  
Plasma Concentrations ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Insulin Resistant ◽  
Remnant Lipoprotein ◽  
Increased Risk ◽  
Resistant Group ◽  
State Plasma

This study was initiated to test the hypothesis that plasma concentrations of remnant lipoproteins would be higher after an overnight fast in insulin-resistant compared to insulin-sensitive volunteers. Forty-three healthy nonobese women were studied, divided into insulin-resistant (n = 21) and insulin-sensitive (n = 22) groups on the basis of their steady state plasma glucose (SSPG) concentration at the end of a 180-min infusion of octreotide acetate, insulin, and glucose. Under these conditions, steady state plasma insulin concentrations are similar in all subjects (∼60μ U/mL), and the higher the SSPG concentrations, the more insulin resistant the individual. By selection, mean (±sem) SSPG concentrations were significantly higher (P &lt; 0.001) in the insulin-resistant group (210 ± 7 vs. 78 ± 3 mg/dL). In addition, the insulin-resistant group had higher triglycerides (198 ± 27 vs. 101 ± 12 mg/dL; P &lt; 0.005) and lower high density lipoprotein cholesterol (48 ± 4 vs. 60 ± 4 mg/dL; P &lt; 0.05) concentrations. Finally, insulin resistance was associated with higher remnant lipoprotein particle concentrations of cholesterol (7.2 ± 0.8 vs. 4.4 ± 0.3; P &lt; 0.005) and triglycerides (22.2 ± 3.4 vs. 8.5 ± 1.0; P &lt; 0.001). All of these differences were seen despite the fact that the two groups were similar in terms of age and body mass index. These results identify additional abnormalities in lipoprotein metabolism that may contribute to the increased risk of coronary heart disease seen in insulin-resistant, nondiabetic subjects (syndrome X).

Within-Individual Variation in Steady State Plasma Levels of Different Neuroleptics and Prolactin

1984 ◽  
Vol 144 (6) ◽  
pp. 625-629 ◽  
Author(s):  
R. G. McCreadie ◽  
Margaret Mackie ◽  
David H. Wiles ◽  
Aksel Jorgensen ◽  
Villy Hansen ◽  
...  
Keyword(s):  
Steady State ◽  
Individual Variation ◽  
Plasma Levels ◽  
State Level ◽  
Drug Analysis ◽  
Plasma Prolactin ◽  
Routes Of Administration ◽  
Chronic Schizophrenics ◽  
Before And After ◽  
State Plasma

SummaryEleven male chronic schizophrenics were given, serially, oral pimozide, fluphenazine, and flupenthixol; the two latter were also given intramuscularly as decanoates in oil. Oral haloperidol was given before and after each drug. Analysis of variance of steady state plasma levels of the different neuroleptics showed considerable within-individual variation in such levels, probably due to differences in absorption and metabolism and between routes of administration. The findings suggest that if a patient fails to respond to one neuroleptic, there may be good pharmacokinetic reasons for switching him to another belonging to a different group, or for giving the same neuroleptic by a different route of administration. The study also showed that previous administration of one neurololeptic may influence the steady state level of another. The various neuroleptics produced different effects on plasma prolactin levels.

scholarly journals Zidovudine does not affect transplacental transfer or systemic clearance of stavudine (2',3'-didehydro-3'-deoxythymidine) in the pigtailed macaque (Macaca nemestrina).

1996 ◽  
Vol 40 (6) ◽  
pp. 1569-1571 ◽  
Author(s):  
A Odinecs ◽  
C Nosbisch ◽  
J D Unadkat
Keyword(s):  
Body Weight ◽  
Steady State ◽  
Amniotic Fluid ◽  
Femoral Vein ◽  
Macaca Nemestrina ◽  
Systemic Clearance ◽  
Transplacental Transfer ◽  
The Mean ◽  
Near Term ◽  
State Plasma

Stavudine (22 micrograms/min/kg of body weight) was infused alone (via the femoral vein) or simultaneously with zidovudine (66 micrograms/min/kg) to three near-term pregnant macaques. No significant differences were found between the mean steady-state plasma stavudine concentrations in the dam (Cssd) and fetus (Cssf), the stavudine concentration in the amniotic fluid (Cssa), and the ratios Cssf/Cssd and Cssa/Cssf when stavudine was infused alone or in combination with zidovudine. The data obtained indicate that zidovudine administration does not affect the transfer of stavudine across the placenta in Macaca nemestrina.

Daily Variations in Steady-State Plasma Concentrations of Carbamazepine and its Metabolites in Epileptic Children

1991 ◽  
Vol 20 (3) ◽  
pp. 237-244 ◽  
Author(s):  
Ronald Hartley ◽  
W. Ian Forsythe ◽  
Bruce McLain ◽  
Pak C. Ng ◽  
Mark D. Lucock
Keyword(s):  
Steady State ◽  
Plasma Concentrations ◽  
Daily Variations ◽  
Epileptic Children ◽  
State Plasma

Phase II Evaluation of the Tyrosine Kinase Inhibitor MLN518 in Patients with Acute Myeloid Leukemia (AML) Bearing a FLT3 Internal Tandem Duplication (ITD) Mutation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1792-1792 ◽  
Author(s):  
Daniel J. De Angelo ◽  
Richard M. Stone ◽  
Mark L. Heaney ◽  
Stephen D. Nimer ◽  
Ronald Paquette ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Steady State ◽  
Phase Ii ◽  
Plasma Concentrations ◽  
Remission Induction ◽  
Western Blots ◽  
Adequate Treatment ◽  
The Mean ◽  
Trough Plasma ◽  
Bone Marrow Blasts

Abstract MLN518 is a small molecule inhibitor of FLT3, PDGFR and c-Kit that is currently being evaluated as a therapy for AML. Previous phase I evaluation of MLN518 showed that it inhibits the phosphorylation of both wild-type and ITD-mutated FLT3 in patients’ leukemic blasts with an IC90 in the range of 100–175 ng/mL. Anti-leukemic activity was also observed, with decreases in both peripheral and bone marrow blasts. Dose-limiting toxicity, consisting of reversible general muscular weakness and/or fatigue was associated with trough plasma MLN518 concentrations > 1000 ng/mL. We are now conducting a phase II study of MLN518 in patients with relapsed or refractory AML and in untreated patients with AML considered unfit for standard AML therapies. Eligibility requires demonstration of the FLT3 ITD mutation in the patient’s blasts. All patients are treated with MLN518 at an initial dose of 525 mg po bid, with provision for dose reduction if MLN518-associated weakness occurs. Twenty patients have been treated with MLN518 in this study, eighteen of whom are currently evaluable (2 patients have recently started therapy). Toxicities associated with MLN518 therapy have included weakness/fatigue, QTc prolongation (relationship to MLN518 uncertain), and nausea and vomiting. MLN518 plasma concentration-time data for the first fourteen patients demonstrates that all patients achieved steady-state trough plasma concentrations > 150 ng/mL. Both inter- and intra-subject variability (%CV) in trough steady-state concentrations were < 30%. Assessment of total and phosphorylated FLT3 in leukemic blasts isolated from peripheral blood was possible in 4 patients. Western blots from blasts obtained before and after MLN518 dosing demonstrated either partial or complete inhibition of FLT3 phosphorylation with MLN518 plasma concentrations > 130 ng/mL. Of the eighteen evaluable patients, response could not be assessed in three because intercurrent illness and/or MLN518-associated toxicity precluded adequate treatment with MLN518 (≥ 14 days). Seven patients experienced progressive AML without evidence of any anti-leukemic effect. Two patients had stable disease for ≥ 50 days and subsequently underwent bone marrow transplantation. Although no complete or partial remissions have been observed, 6 patients have demonstrated evidence of an anti-leukemic effect with decreases in both peripheral and bone marrow blasts of 1-3 months duration. In these 6 patients the mean decrease in the absolute peripheral blast count was 92%, with a range of 85–100%. The mean decrease in the bone marrow blast percentage was 62%, with a range of 44–94%. We conclude that MLN518 has anti-leukemic activity in FLT3 ITD-mutated AML and should be further evaluated as a component of remission-induction and/or maintenance therapy in this disease.

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