Pharmacokinetics of drugs in blood V: Aberrant blood and plasma concentration profiles of methotrexate during intravenous infusion

1986 ◽  
Vol 7 (5) ◽  
pp. 487-494 ◽  
Author(s):  
Myung G. Lee ◽  
Chung Y. Lui ◽  
Win L. Chiou
Keyword(s):  
Plasma Concentration ◽  
Intravenous Infusion ◽  
Concentration Profiles ◽  
Drugs In Blood

Angiotensin II infusion increases vasopressin, ACTH, and 11-hydroxycorticosteroid secretion

1978 ◽  
Vol 234 (1) ◽  
pp. R66-R71 ◽  
Author(s):  
D. J. Ramsay ◽  
L. C. Keil ◽  
M. C. Sharpe ◽  
J. Shinsako
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Plasma Concentration ◽  
Plasma Renin Activity ◽  
Plasma Levels ◽  
Intravenous Infusion ◽  
Plasma Renin ◽  
Acth Secretion ◽  
Plasma Vasopressin ◽  
Bilateral Carotid

The effects of intravenous infusion of Asp1. Ile5-angiotensin II on blood pressure, plasma vasopressin, ACTH and 11-hydroxycorticosteroid levels and on plasma renin activity were studied in five trained, conscious dogs. The dogs were prepared with bilateral carotid loops. Infusion of angiotensin II at rates of 5, 10, and 20 ng/kg.min raised its plasma concentration from 23 +/- 7 to 48 +/- 8, 125 +/- 8, and 187 +/- 21 pg/ml, respectively. The lowest rate of infusion was mildly pressor, the two higher rates more so. All rates of infusion promptly increased vasopressin levels and depressed renin levels. The two higher rates also stimulated ACTH, although with a latency of 30-45 min. Since the rates of infusion of angiotensin II employed produced plasma levels within the physiological range, it is suggested that peripherally generated angiotensin II may play an important role in the regulation of vasopressin, and ACTH secretion.

CC-486 (Oral Azacitidine) Following Allogeneic Hematopoietic Stem Cell Transplantation (AlloHSCT) in Patients with Myelodysplastic Syndromes (MDS) or Acute Myeloid Leukemia (AML)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 990-990 ◽  
Author(s):  
Basem M. William ◽  
Marcos de Lima ◽  
Betul Oran ◽  
Richard Champlin ◽  
Esperanza B Papadopoulos ◽  
...  
Keyword(s):  
Stem Cell ◽  
Plasma Concentration ◽  
Febrile Neutropenia ◽  
Research Funding ◽  
Concentration Profiles ◽  
Employment Equity ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Equity Ownership ◽  
Concomitant Medications

Abstract Background: Disease relapse and graft vs host disease (GvHD) following alloHSCT are major causes of treatment (Tx) failure in patients (pts) with MDS and AML (Paietta, 2012). Studies of parenteral azacitidine, an epigenetic modifier, have shown efficacy in preventing post-transplant relapse in MDS and AML pts, and possibly reducing GvHD severity (Platzbecker, 2012; de Lima, 2010). Azacitidine maintenance after alloHSCT may enhance graft vs leukemia (GvL) effects and reduce GvHD by expansion of regulatory T cells (Goodyear, 2010, 2012). CC-486 is a novel oral formulation of azacitidine which, as well as potentially allowing easier administration over extended schedules, could increase the duration of drug exposure to residual malignant cells. We now report preliminary results from a prospective phase I/II dose-finding study of CC-486 as maintenance Tx after alloHSCT in pts with MDS or AML. Objective: To evaluate the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), pharmacokinetics (PK), and safety outcomes of CC-486 following alloHSCT in pts with MDS or AML. Methods: Pts with WHO-defined MDS or AML who have undergone alloHSCT with myeloablative (MAC) or reduced-intensity conditioning (RIC) regimens and who had sibling or unrelated donors with ≤1 antigen mismatch at the HLA-A, -B, -C, -DRB1 or -DQB1 locus, are enrolled. CC-486 Tx is initiated between days (d) 42 and 84 after alloHSCT. Pts receive prophylactic Tx for GvHD and infections per institutional standard. A standard 3x3 MTD design is being used to evaluate 4 dosing schedules: CC-486 200 mg or 300 mg QD, administered for 7 d (Cohorts 1 and 2) or 14 d (Cohorts 3 and 4) of repeated 28d Tx cycles. MTD determination is based on DLT that occur during the first 2 Tx cycles (pts are not evaluable if unable to complete 2 Tx cycles for reasons other than a DLT). Adverse events (AEs) are graded using NCI-CTCAE v4.0. Pts are followed for safety, incidence of acute and chronic GvHD, and relapse. PK of azacitidine after CC-486 administration, alone or with standard concomitant medications, are evaluated on d 1 of CC-486 Tx cycles 1 and 2. Results: At data cut-off (7/17/2014), outcome data were available for 7 pts enrolled in the first 2 cohorts (Table): 1 pt had IPSS Int-2 MDS and 6 had AML with high-risk features. Stem cell source was from bone marrow (n=2) or peripheral blood (n=5) from unrelated (n=5) or sibling (n=2) donors. Two pts had 1 antigen mismatch and 5 had a full match.Conditioning included MAC (n=3) and RIC (n=4) regimens. One pt in Cohort 2 was not evaluable for DLT or PK assessments due to early discontinuation (AML relapse) during the first CC-486 Tx cycle. Of the 6 evaluable pts, 4 completed ≥6 CC-486 Tx cycles and 2 ongoing pts had not reached 6 cycles on-study at data cut-off (Table). One pt who had GvHD before CC-486 Tx subsequently withdrew from the study after developing febrile neutropenia and diarrhea related to GvHD of the bowel; 1 pt withdrew for personal reasons; and 1 pt discontinued after 6 Tx cycles due to relapse. At data cut-off, 3 pts remained on-study, all with continued CR (Table). No pt in Cohort 2 developed GvHD. For all pts, most AEs were grade 1-2. Grade 3-4 AEs were reported for 2 pts: both had nausea and vomiting, which were controlled with antiemetic agents upon onset; 1 also had device-related infection and dyspnea, and 1 also had febrile neutropenia and rash. No DLT emerged with these CC-486 regimens and no pt experienced secondary graft failure. Overall azacitidine plasma concentration profiles (Figure) and PK parameters were similar following CC-486 given alone or with concomitant medications, and were within range of values observed following similar CC-486 doses in pts with MDS, CMML, and AML (Garcia-Manero, 2011). The AUC range for oral CC-486 is ~10% of that seen with subcutaneous azacitidine administered at 75 mg/m2 (Garcia-Manero, 2011). Conclusion: Preliminary data from this analysis suggest that CC-486 administered at doses of 200 or 300 mg QD for 7 days every 4 weeks is safe and well tolerated in the post-transplant setting. Overall, azacitidine plasma concentration profiles and PK parameters were not affected by use of concomitant medications. No DLT and a low rate of GvHD support the ongoing evaluation of 14d extended CC-486 dosing regimens in this ongoing study, as a preliminary to a prospective, randomized trial of this new agent post-transplant. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures de Lima: Celgene: Consultancy. Champlin:Celgene: Consultancy. Giralt:Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau. Scott:Celgene: Consultancy, Honoraria, Research Funding. Hetzer:Celgene: Employment, Equity Ownership. Wang:Celgene: Employment, Equity Ownership. Laille:Celgene: Employment, Equity Ownership. Skikne:Celgene: Employment, Equity Ownership. Craddock:Celgene: Honoraria, Research Funding.

Effects of an Intravenous Infusion of Noradrenaline on the Plasma Concentration of Free and Sulfoconjugated Catecholamines in Anesthetized Dogs

Pharmacology ◽  
1986 ◽  
Vol 32 (2) ◽  
pp. 90-100 ◽  
Author(s):  
J.L. Cuche ◽  
G. Jondeau ◽  
G. Ruget ◽  
F. Selz ◽  
J.C. Piga ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Intravenous Infusion ◽  
Anesthetized Dogs

Plasma concentration profiles of ketamine and norketamine after administration of various ketamine preparations to healthy Japanese volunteers

2002 ◽  
Vol 24 (1) ◽  
pp. 37-43 ◽  
Author(s):  
Yoshitsugu Yanagihara ◽  
Michiteru Ohtani ◽  
Satoru Kariya ◽  
Katsuyoshi Uchino ◽  
Teiko Hiraishi ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Concentration Profiles

scholarly journals The ‘anomalous’ absorption of labelled and unlabelled vitamin C in man

2005 ◽  
Vol 93 (5) ◽  
pp. 627-632 ◽  
Author(s):  
Leslie J. C. Bluck ◽  
Kerry S. Jones ◽  
W. Andy Coward ◽  
Christopher J. Bates
Keyword(s):  
Plasma Concentration ◽  
Stable Isotope ◽  
Vitamin C ◽  
Experimental Results ◽  
Concentration Profiles ◽  
Model Structure ◽  
Limited Information ◽  
Anomalous Absorption ◽  
Plasma Model ◽  
Isotope Measurement

Previous studies of vitamin C absorption in man using stable isotope probes have given results which cannot easily be reconciled with those obtained using non-isotope measurement. In order to investigate some of the apparent paradoxes we have conducted a study using two consecutive doses of vitamin C, one labelled and one unlabelled, given 90 min apart. Compatibility of the experimental results with two feasible models was investigated. In Model 1, ingested vitamin C enters a pre-existing pool before absorption, which occurs only when a threshold is exceeded; in Model 2, ingested vitamin C is exchanged with a pre-existing flux before absorption. The key difference between these two models lies in the predicted profile of labelled material in plasma. Model 1 predicts that the second unlabelled dose will produce a secondary release of labelled vitamin C which will not be observed on the basis of Model 2. In all subjects Model 1 failed to predict the observed plasma concentration profiles for labelled and unlabelled vitamin C, but Model 2 fitted the experimental observations. We speculate on possible physiological explanations for this behaviour, but from the limited information available cannot unequivocally confirm the model structure by identifying the source of the supposed flux.

scholarly journals Pharmacokinetics of Epinastine and a Possible Mechanism for Double Peaks in Oral Plasma Concentration Profiles.

2001 ◽  
Vol 24 (7) ◽  
pp. 790-794 ◽  
Author(s):  
Taro OGISO ◽  
Masafusa KASUTANI ◽  
Hiroaki TANAKA ◽  
Masahiro IWAKI ◽  
Tadatoshi TANINO
Keyword(s):  
Plasma Concentration ◽  
Concentration Profiles ◽  
Double Peaks
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