scholarly journals Busulfan pharmacokinetics using a single daily high-dose regimen in children with acute leukemia

Blood ◽  
1994 ◽  
Vol 84 (7) ◽  
pp. 2357-2362 ◽  
Author(s):  
PJ Shaw ◽  
CE Scharping ◽  
RJ Brian ◽  
JW Earl
Keyword(s):  
Acute Leukemia ◽  
Dose Regimen ◽  
Peak Plasma ◽  
Area Under The Curve ◽  
Systemic Exposure ◽  
Single Daily Dose ◽  
Pharmacokinetic Parameters ◽  
High Dose ◽  
Peak Plasma Level ◽  
Daily Dose

Abstract The pharmacokinetics of busulfan, given as a single daily dose (either 4 mg/kg or 150 mg/m2), was determined in 22 children undergoing bone marrow transplantation for acute leukemia. The single daily dose regimen showed similar pharmacokinetics to previously reported regimens of 4 x 1 mg/kg, except for fourfold higher mean peak plasma levels and negligible trough levels. Daily systemic exposure for single dose regimens based on weight (4 mg/kg) or surface area (150 mg/m2), respectively were very similar to regimens of (4 x 1 mg/kg) or (4 x 37.5 mg/m2). Dose (milligrams per kilogram), peak plasma level, and area under the curve (AUC) were all higher in 12 children treated with 150 mg/m2 busulfan than in 9 children treated with 4 mg/kg. AUC was age dependent for the 4 mg/kg dose but not for the 150 mg/m2 dose. The use of a 150 mg/m2 dose allows escalation of the dose above 4 mg/kg, eliminating the tendency for younger children to receive lower systemic exposure. Little toxicity was observed in this study. Clearance and distribution volume correlated negatively with age, and AUC correlated positively with dose (milligram per kilogram). Administration of busulfan as crushed rather than whole tablets reduced the delay time for appearance of busulfan in plasma but had no effect on absorption or other pharmacokinetic parameters.

scholarly journals Busulfan pharmacokinetics using a single daily high-dose regimen in children with acute leukemia

Blood ◽  
1994 ◽  
Vol 84 (7) ◽  
pp. 2357-2362
Author(s):  
PJ Shaw ◽  
CE Scharping ◽  
RJ Brian ◽  
JW Earl
Keyword(s):  
Acute Leukemia ◽  
Dose Regimen ◽  
Peak Plasma ◽  
Area Under The Curve ◽  
Systemic Exposure ◽  
Single Daily Dose ◽  
Pharmacokinetic Parameters ◽  
High Dose ◽  
Peak Plasma Level ◽  
Daily Dose

The pharmacokinetics of busulfan, given as a single daily dose (either 4 mg/kg or 150 mg/m2), was determined in 22 children undergoing bone marrow transplantation for acute leukemia. The single daily dose regimen showed similar pharmacokinetics to previously reported regimens of 4 x 1 mg/kg, except for fourfold higher mean peak plasma levels and negligible trough levels. Daily systemic exposure for single dose regimens based on weight (4 mg/kg) or surface area (150 mg/m2), respectively were very similar to regimens of (4 x 1 mg/kg) or (4 x 37.5 mg/m2). Dose (milligrams per kilogram), peak plasma level, and area under the curve (AUC) were all higher in 12 children treated with 150 mg/m2 busulfan than in 9 children treated with 4 mg/kg. AUC was age dependent for the 4 mg/kg dose but not for the 150 mg/m2 dose. The use of a 150 mg/m2 dose allows escalation of the dose above 4 mg/kg, eliminating the tendency for younger children to receive lower systemic exposure. Little toxicity was observed in this study. Clearance and distribution volume correlated negatively with age, and AUC correlated positively with dose (milligram per kilogram). Administration of busulfan as crushed rather than whole tablets reduced the delay time for appearance of busulfan in plasma but had no effect on absorption or other pharmacokinetic parameters.

Treatment of hyperthyroidism with a small single daily dose of methimazole

1988 ◽  
Vol 119 (1) ◽  
pp. 139-144 ◽  
Author(s):  
Yasuo Mashio ◽  
Mutsuo Beniko ◽  
Akemi Ikota ◽  
Hiroaki Mizumoto ◽  
Haruhiko Kunita
Keyword(s):  
Divided Dose ◽  
Dose Regimen ◽  
Single Daily Dose ◽  
Once Daily ◽  
Daily Dose ◽  
The Mean ◽  
Time Required ◽  
Daily Dose Regimen ◽  
Mean Time ◽  
Immunoglobulin Levels

Abstract. A prospective randomized trial with the conventional divided doses (10 mg 3 times daily, N = 29) and a small single daily dose (15 mg once daily, N = 25) of methimazole for the treatment of Graves' hyperthyroidism was performed. Within 8 weeks, almost 80% of the patients in both groups became euthyroid. The mean time required to achieve the euthyroid state was 6.0 ± 2.8 and 6.0 ± 3.8 weeks, respectively. TSH binding inhibitor immunoglobulin was found in about 90% of the patients in both groups before methimazole treatment. However, a gradual fall of its levels was observed in nearly all patients after treatment. There was no difference in the mean levels of TSH binding inhibitor immunoglobulin between the two groups during therapy. We conclude that the single daily dose regimen of 15 mg of methimazole will control Graves' hyperthyroidism in most patients, and TSH binding inhibitor immunoglobulin levels decrease in this regimen in the same way as with the conventional divided dose regimen (10 mg 3 times daily).

scholarly journals Emulsification by TPGS or Quillaja Extract Increased Absorption and Affected Metabolism of Berberine in Humans

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 381-381
Author(s):  
Yavuz Yagiz ◽  
Gary Wang ◽  
Liwei Gu
Keyword(s):  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Area Under The Curve ◽  
Total Content ◽  
Compartment Model ◽  
Analysis Of Covariance ◽  
High Tech ◽  
Pharmacokinetic Parameters ◽  
Funding Sources ◽  
Human Volunteers

Abstract Objectives Berberine is a botanical alkaloid used widely for the prevention of several diseases. However, the absorption rate of berberine is less than 1% in human. The objectives of this study were to determine whether emulsification by TPGS or Quillaja extract affect the absorption and metabolism of orally ingested berberine in human volunteers. Methods Twelve healthy subjects (7 male and 5 females, 21–50-year-old) participated this study. Each subject received 800 mg berberine in a powder form or emulsified with TPGS or Quillaja extract using a randomized crossover design with one-week washout period. Blood samples were collected at 0, 0.5, 1, 2, 3, 4, 6, 8, and 12 hours after dose. Plasma was hydrolyzed with glucuronidase and sulfatase before total content of berberine and its metabolites were analyzed on LC/MS/MS. Free forms of metabolites were determined in plasma without hydrolysis. Pharmacokinetic parameters were calculated using a non-compartment model before they were compared by analysis of covariance. Results The area under the curve (AUC) and peak plasma concentration (Cmax) of berberine was 6.6 μM.hr and 0.9 μM in participants received berberine powder. They were increased to 18.3 μM.hr and 4.5 μM by TPGS emulsification and 28 μM.hr and 5.1 μM by Quillaja extract emulsification, respectively. Berberrubine and demethylberberine were major metabolites of berberine. The AUC of free Berberrubine and demethylberberine was increased by 1.9 fold and 1.6 fold by TPGS and 5.9 folds and 2.7 folds by Quillaja extract, respectively, compared to berberine powder. Participants received berberine powder had AUC of 254 μM.hr and Cmax of 33 μM for total berberrubine. TPGS emulsification increased these values to 425 μM.hr and 54 μM, while Quillaja extract increased them to 341 μM.hr and 44 μM, respectively. Significant increases of AUC and Cmax were also observed for total demethylberberine by TPGS or Quillaja extract emulsification. Conclusions Emulsification of berberine with TPGS or Quillaja extract significantly increased the absorption of berberine and its metabolites in human compared to berberine supplement without emulsifiers. Funding Sources Florida High Tech Corridor Council and Designs for Health.

Single Daily Dose of I.V. Busulfan (BU) in Pediatric Patients. Feasibility, Pharmacokinetics (PK) and Toxicity.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1151-1151 ◽  
Author(s):  
Morris Kletzel ◽  
David Jacobsohn ◽  
William Tse ◽  
Reggie Duerst
Keyword(s):  
Pediatric Patients ◽  
Prospective Trial ◽  
Young Patients ◽  
Area Under The Curve ◽  
Test Dose ◽  
Single Daily Dose ◽  
Severe Combined Immune Deficiency ◽  
Stem Cell Source ◽  
Daily Dose ◽  
Improve Compliance

Abstract Administration of oral BU is a challenge in pediatric patients. The I.V preparation can improve compliance and eliminate variability in absorption. The metabolism and clearance of BU is age dependant. A prospective trial using a single daily dose of I.V. BU as part of a reduced Intensity Regimen was undertaken. Patients were enrolled after proper informed consent was signed... The regimen consisted of a test dose of BU (0.8mg/kg as a 2 hr infusion) on day -10, Fludarabine 25mg/m2/day from day-10 to -5, BU 3.2 mg/Kg/Day on days -5 ,-4.and rabbit ATG 2mg/kg daily on days -4 to-1. Cells were infused on day 0. The stem cell source were UCB (n=4), MUD (n=7) and MSD (n=1). PK samples (2, 4, 6,8,12 hrs) were obtained and submitted to the Seattle Cancer Care Alliance for determination of the Area Under the Curve (AUC) and clearance for BU. Twelve patients were enrolled (8F, 4M), median age 8 (0.5–16), median weight 22.6 kg (4.3–58.8) with the following diagnoses: Neuroblastoma (n=3), ALL (n=3), CML (n=2), Aplastic Anemia and X linked Lymphoprolipherative Disease, Ommen’s syndrome, Severe Combined Immune Deficiency. An AUC of 800–1200 and 3200–4800 uMol*min were targeted for the test dose and the single daily dose respectively. The median AUC for the test dose was 1003 uMol*min (804–1315), and the median clearance was 3.1 (ml/min)/Kg (2.4–7.3). The median AUC for the single daily dose was 3512 uMol*min (1511–4097) and the clearance 3.4 (ml/min)/kg (2.8–6.8). After the test dose 4 patients had their dose adjusted (2 patients lower and 2 patients higher). In the very young patients (< 1 year of age) the AUC of the single daily dose could not be predicted due to abnormal clearance. No instances of VOD or seizures were observed. Full donor chimerism was achieved in 8 patients in a median of 23 days (14–53), 2 patients developed graft failure, 1 patient was not evaluable for engraftment due to early TRM from pre-existing CMV pneumonia and 1 patient is too early. In conclusion, a single daily dose of I.V. BU is feasible, a test dose can be a predictor of the single daily dose AUC except in the very young, No regimen related toxicity was observed and engraftment was prompt and complete in 8 evaluable patients.

scholarly journals Terbinafine in Combination with Other Antifungal Agents for Treatment of Resistant or Refractory Mycoses: Investigating Optimal Dosing Regimens Using a Physiologically Based Pharmacokinetic Model

2013 ◽  
Vol 58 (1) ◽  
pp. 48-54 ◽  
Author(s):  
Michael J. Dolton ◽  
Vidya Perera ◽  
Lisa G. Pont ◽  
Andrew J. McLachlan
Keyword(s):  
Dose Regimen ◽  
Antifungal Agents ◽  
Pbpk Model ◽  
Standard Dose ◽  
Systemic Exposure ◽  
High Dose ◽  
Unbound Fraction ◽  
Minimum Concentration ◽  
Physiologically Based Pharmacokinetic ◽  
Physiologically Based

ABSTRACTTerbinafine is increasingly used in combination with other antifungal agents to treat resistant or refractory mycoses due to synergisticin vitroantifungal activity; high doses are commonly used, but limited data are available on systemic exposure, and no assessment of pharmacodynamic target attainment has been made. Using a physiologically based pharmacokinetic (PBPK) model for terbinafine, this study aimed to predict total and unbound terbinafine concentrations in plasma with a range of high-dose regimens and also calculate predicted pharmacodynamic parameters for terbinafine. Predicted terbinafine concentrations accumulated significantly during the first 28 days of treatment; the area under the concentration-time curve (AUC)/MIC ratios and AUC for the free, unbound fraction (fAUC)/MIC ratios increased by 54 to 62% on day 7 of treatment and by 80 to 92% on day 28 compared to day 1, depending on the dose regimen. Of the high-dose regimens investigated, 500 mg of terbinafine taken every 12 h provided the highest systemic exposure; on day 7 of treatment, the predicted AUC, maximum concentration (Cmax), and minimum concentration (Cmin) were approximately 4-fold, 1.9-fold, and 4.4-fold higher than with a standard-dose regimen of 250 mg once daily. Close agreement was seen between the concentrations predicted by the PBPK model and the observed concentrations, indicating good predictive performance. This study provides the first report of predicted terbinafine exposure in plasma with a range of high-dose regimens.

scholarly journals The effects of oral administration of Cola nitida on the pharmacokinetic profile of metoclopramide in rabbits

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Cecilia Nwadiuto Amadi ◽  
Wisdom Izuchukwu Nwachukwu
Keyword(s):  
Drug Interaction ◽  
Plasma Concentration ◽  
Oral Administration ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Elimination Rate ◽  
Area Under The Curve ◽  
Pharmacokinetic Profile ◽  
Pharmacokinetic Parameters ◽  
Cola Nitida

Abstract Background Cola nitida is commonly chewed in many West African cultures to ease hunger pangs and sometimes for their stimulant and euphoriant qualities. Metoclopramide is a known substrate for P-gp, SULT2A1 and CYP2D6 and studies have revealed that caffeine- a major component of Cola nitida can induce P-glycoprotein (P-gp), SULT2A1 and SULT1A1, hence a possible drug interaction may occur on co-administration. The aim of this study was to investigate the pharmacokinetic interactions of Cola nitida and metoclopramide in rabbits. Methods The study was performed in two stages using five healthy male rabbits with a 1-week washout period between treatments. Stage one involved oral administration of metoclopramide (0.5 mg/kg) alone while in the second stage, metoclopramide (0.5 mg/kg) was administered concurrently with Cola nitida (0.7 mg/kg). Blood samples were collected after each stage at predetermined intervals and analyzed for plasma metoclopramide concentration using HPLC. Results Compared with control, the metoclopramide/Cola nitida co-administration produced a decrease in plasma concentration of metoclopramide at all the time intervals except at the 7th hour. The following pharmacokinetic parameters were also decreased: area under the curve (51%), peak plasma concentration (39%), half-life (51%); while an increase in elimination rate constant (113%) and clearance rate (98%) were noted indicating rapid elimination of the drug. A minimal decrease in absorption rate (10%) was also observed. Conclusions The results of this study reveal a possible herb-drug interaction between Cola nitida and metoclopramide.

High dose single-agent paclitaxel in a hemodialysis patient with advanced ovarian cancer: a case report with pharmacokinetic analysis and review of the literature

2008 ◽  
Vol 18 (3) ◽  
pp. 564-570 ◽  
Author(s):  
M. BAUR ◽  
B. FAZENY-DOERNER ◽  
S. J. OLSEN ◽  
C. DITTRICH
Keyword(s):  
Ovarian Cancer ◽  
Plasma Concentration ◽  
Peak Plasma ◽  
Single Agent ◽  
Objective Response ◽  
Advanced Ovarian Cancer ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
High Dose ◽  
Severe Toxicity

There exists only scarce data on the pharmacokinetics of paclitaxel in patients with renal insufficiency. A 53-year-old woman on hemodialysis was treated with paclitaxel for relapsed ovarian cancer. Paclitaxel was administered as a 3-h infusion at 175, 225, and 300 mg/m2 on nonhemodialysis days. The pharmacokinetic analysis revealed independence of the pharmacokinetic parameters for paclitaxel from the extent of renal (dys-)function. The peak plasma concentration of the 300 mg/m2 dose level before and after dialysis was 23.05 and 21.01 ng/mL, respectively, proving that paclitaxel was not dialysable. The area under the plasma concentration versus time curve for the standard and highest dose of paclitaxel was 12,200 ng·h/mL in mean and 40,936 ng·h/mL, respectively. The absence of marked side effects at all dose levels was in line with the independence of the pharmacokinetic parameters for paclitaxel from renal function. No objective response was found, but a marked improvement of symptoms from gastrointestinal obstruction as well as a decrease in the serum CA125 level were observed. Patients with terminal renal failure undergoing hemodialysis tolerate conventional and even high doses of paclitaxel without experiencing severe toxicity.

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