scholarly journals Pharmacokinetics of conventional formulation versus fat emulsion formulation of amphotericin B in a group of patients with neutropenia.

1996 ◽  
Vol 40 (3) ◽  
pp. 609-612 ◽  
Author(s):  
A Ayestarán ◽  
R M López ◽  
J B Montoro ◽  
A Estíbalez ◽  
L Pou ◽  
...  
Keyword(s):  
Steady State ◽  
Amphotericin B ◽  
Central Compartment ◽  
Volume Of Distribution ◽  
Fat Emulsion ◽  
Maximum Serum ◽  
Elimination Phase ◽  
Group I ◽  
Emulsion Formulation ◽  
Group Ii

The pharmacokinetics of amphotericin B administered in a conventional 5% dextrose (glucose) (5% D) solution and in a 20% fat emulsion formulation (Intralipid; 20% IL) were compared in 16 patients (mean age, 42 years [range, 18 to 70 years]) who had been hospitalized for hematological malignancies and with proven or suspected fungal infections. All of the patients received 50 mg (approximately 1 mg/kg of body weight per day) of amphotericin B daily in random order, either as a 50-ml lipid emulsion (20% IL) (group I) or in 500 ml of 5% D (group II). Five serum samples were taken during the 24 h after drug administration, and the levels of amphotericin B were measured by high-pressure liquid chromatography. Serum amphotericin B concentrations declined rapidly during the first 6 h, and subsequent measurements revealed a slow terminal elimination phase in both groups. The maximum serum amphotericin B concentration was significantly lower when the drug was administered in 20% IL (1.46 +/- 0.61 versus 2.83 +/- 1.17 micrograms/ml; P = 0.02). The area under the concentration-time curve from 0 to 24 h was also much lower in group I (17.22 +/- 11.15 versus 28.98 +/- 15.46 micrograms.h/ml). The half-life of the distribution phase was approximately three times longer in group I (2.92 +/- 2.34 h versus 0.64 +/- 0.24 h; P = 0.011). Conversely, the half-lives of the elimination phase were approximately equal in the two groups (11.44 +/- 5.18 versus 15.23 +/- 5.25 h). The mean residence times were also similar in both groups (19.41 +/- 11.13 versus 19.65 +/- 7.86 h). The clearance and the steady-state volume of distribution of amphotericin B in group I were about twice as great as those in group II (62.97 +/- 35.51 versus 33.01 +/- 14.33 ml/kg/h and 1,043.92 +/- 512.10 versus 562.32 +/- 152.05 ml/kg [P = 0.034], respectively). Finally, the volume of distribution in the central compartment was greater in group I than in group II (618.17 +/- 231.80 versus 328.19 +/- 151.71 ml/kg; P = 0.013), but there were no differences in the volume of distribution in the peripheral compartment (425.75 +/- 352.87 versus 234.14 +/- 75.92 ml/kg). These results suggest that amphotericin B has a different pharmacokinetic profile when it is administered in 20% IL than when it is administered in the standard 5% D form and that the main difference is due to a clear-cut difference in the steady-state volume of distribution, especially that in the central compartment.

Recycling of an amino acid label with prolonged isotope infusion: implications for kinetic studies

1985 ◽  
Vol 248 (4) ◽  
pp. E482-E487 ◽  
Author(s):  
W. F. Schwenk ◽  
E. Tsalikian ◽  
B. Beaufrere ◽  
M. W. Haymond
Keyword(s):  
Amino Acids ◽  
Steady State ◽  
Amino Acid ◽  
Infusion Rate ◽  
Kinetic Studies ◽  
Intracellular Pool ◽  
Group I ◽  
Group Ii ◽  
Plasma Leucine ◽  
Amino Acid Label

To investigate whether recycling of a labeled amino acid would occur after 24 h of infusion, two groups of normal volunteers were infused with [3H]leucine and alpha-[14C]-ketoisocaproate for 4 h and [2H3]leucine for either 4 or 24 h (groups I and II, respectively). Entry of [2H3 )leucine at steady state into the plasma space was indistinguishable from its infusion rate for group I but 30% higher (P less than 0.001) than this rate for group II, demonstrating significant recycling of label. After discontinuation of the infusions, isotope disappearance from the plasma space was followed for 2 h. The 3H and 14C decay data for both groups suggest that plasma leucine and alpha-ketoisocaproate are derived from a single intracellular pool in the postabsorptive state. In group I, the 3H and 2H labels decayed identically; whereas, in group II, the decay of [2H3]-leucine and alpha-[2H3]ketoisocaproate was slower (P less than 0.01) than the decay of [3H]leucine and alpha-[3H]ketoisocaproate, confirming re-entry of label after a 24-h infusion. Therefore kinetic values calculated from models assuming no recycling of labeled amino acids are most likely not quantitative and must be interpreted with care when flux does not change or decreases.

scholarly journals Absence of Effect of Rufloxacin on Theophylline Pharmacokinetics in Steady State

1998 ◽  
Vol 42 (9) ◽  
pp. 2359-2364 ◽  
Author(s):  
Martina Kinzig-Schippers ◽  
Uwe Fuhr ◽  
Marina Cesana ◽  
Carola Müller ◽  
A. Horst Staib ◽  
...  
Keyword(s):  
Steady State ◽  
Adverse Events ◽  
Compartment Model ◽  
Volume Of Distribution ◽  
Reversed Phase ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Elimination Phase ◽  
Once Daily ◽  
Model Independent

ABSTRACT Several quinolone antibacterial agents are known to inhibit the metabolism of theophylline, with the potential to cause adverse events due to raised theophylline concentrations during coadministration. A randomized crossover study was therefore conducted with 12 healthy male volunteers (ages, 23 to 34 years; body weight, 64 to 101 kg) to evaluate a possible interaction between rufloxacin and theophylline. Both drugs were administered at steady state. Following the administration of an oral loading dose of 400 mg on day 1, rufloxacin was given orally at 200 mg once daily on days 2 to 7 during one period only. During both periods, 146 mg of theophylline was administered orally twice daily for 3 days (which were days 4 to 6 of the rufloxacin coadministration period) and intravenously once the next morning to test for an interaction. Theophylline and rufloxacin concentrations were measured by reversed-phase high-pressure liquid chromatography, the pharmacokinetics of theophylline at steady state following administration of the last dose were calculated by compartment-model-independent methods. To compare the treatments, analysis of variance-based point estimates and 90% confidence intervals (given in parentheses) were calculated for the mean ratios of the pharmacokinetic parameters from the test (rufloxacin coadministration) over those from the reference (theophylline without rufloxacin) period. These were as follows: maximum concentration at steady state, 1.01 (0.96 to 1.07); area under the concentration-time curve from 0 to 12 h, 0.98 (0.94 to 1.02); half-life, 0.99 (0.95 to 1.03); total clearance at steady state, 1.02 (0.99 to 1.06); and volume of distribution in the elimination phase, 1.01 (0.97 to 1.05). In conclusion, rufloxacin did not affect theophylline pharmacokinetics at steady state. Therefore, therapeutic coadministration of rufloxacin and theophylline is not expected to cause an increased incidence of theophylline-related adverse events.

scholarly journals Should Voriconazole be the Primary Therapy for Chronic Invasive Sinus Aspergillosis (CISA)?

2011 ◽  
Vol 4 (1) ◽  
pp. 27-37 ◽  
Author(s):  
Sandeep Bansal
Keyword(s):  
Amphotericin B ◽  
Antifungal Agents ◽  
Successful Outcome ◽  
Fungal Sinusitis ◽  
Primary Therapy ◽  
Group I ◽  
Disease Definition ◽  
Significant Difference ◽  
Group Ii ◽  
Chronic Invasive

ABSTRACT Introduction Invasive sinus aspergillosis infection has been reported with increasing frequency in the last decade, especially, in immunocompromised patients with chronic invasive sinus aspergillosis (CISA). The gold standard for treatment has been wide surgical debridement, intravenous administration of antifungal agents, such as amphotericin B, but the prognosis remains poor. Newer antifungal agents are being tried but no standard treatment option with new antifungal agents has yet been established for chronic invasive fungal sinusitis. Therefore, we undertook this study to evaluate the efficacy of voriconazole in patients of chronic invasive sinus aspergillosis. Materials and methods This study is a prospective randomized unblinded study with primary aim of evaluating the feasibility and effectivity of voriconazole in patients of chronic invasive sinus aspergillosis with intraorbital or intracranial extension, and secondarily to compare voriconazole with amphotericin B therapy in patients with chronic invasive sinus aspergillosis. Observations and results Thirty-three patients who fulfilled the eligibility criteria were included in this study. There were 18 patients enrolled in group I who received amphotericin therapy and 15 patients in group II who received voriconazole therapy. Out of 33 patients, 9 patients had complete response, 10 had partial response, in eight patients disease became stable and there were seven failures. Overall 50% patients had a successful outcome in group I, whereas 60% had a successful outcome in group II receiving oral voriconazole. On comparing only in extradural group, 5/10 had a successful outcome in group I receiving amphotericin B, whereas 8/12 (66.7%) had a successful outcome in group 2 receiving voriconazole. There was significant difference between adverse reactions of the two drugs, with amphotericin B having a significant renal and cardiotoxicity as compared to voriconazole; though patients on voriconazole developed skin rashes which were transient and disappeared on completion of the therapy. Conclusion The present series demonstrates that oral voriconazole can be the primary line of therapy in chronic invasive sinus aspergillosis in carefully monitored immunocompetent cases. Multicentric, randomized studies are required to define disease definition, duration and successful outcome.

scholarly journals Should Voriconazole be the Primary Therapy for Chronic Invasive Sinus Aspergillosis (CISA)?

2011 ◽  
Vol 4 (1) ◽  
pp. 21-26
Author(s):  
Sandeep Bansal
Keyword(s):  
Amphotericin B ◽  
Antifungal Agents ◽  
Successful Outcome ◽  
Fungal Sinusitis ◽  
Primary Therapy ◽  
Group I ◽  
Disease Definition ◽  
Significant Difference ◽  
Group Ii ◽  
Chronic Invasive

ABSTRACT Introduction Invasive sinus aspergillosis infection has been reported with increasing frequency in the last decade, especially, in immunocompromised patients with chronic invasive sinus aspergillosis (CISA). The gold standard for treatment has been wide surgical debridement, intravenous administration of antifungal agents, such as amphotericin B, but the prognosis remains poor. Newer antifungal agents are being tried but no standard treatment option with new antifungal agents has yet been established for chronic invasive fungal sinusitis. Therefore, we undertook this study to evaluate the efficacy of voriconazole in patients of chronic invasive sinus aspergillosis. Materials and methods This study is a prospective randomized unblinded study with primary aim of evaluating the feasibility and effectivity of voriconazole in patients of chronic invasive sinus aspergillosis with intraorbital or intracranial extension, and secondarily to compare voriconazole with amphotericin B therapy in patients with chronic invasive sinus aspergillosis. Observations and results Thirty-three patients who fulfilled the eligibility criteria were included in this study. There were 18 patients enrolled in group I who received amphotericin therapy and 15 patients in group II who received voriconazole therapy. Out of 33 patients, 9 patients had complete response, 10 had partial response, in eight patients disease became stable and there were seven failures. Overall 50% patients had a successful outcome in group I, whereas 60% had a successful outcome in group II receiving oral voriconazole. On comparing only in extradural group, 5/10 had a successful outcome in group I receiving amphotericin B, whereas 8/12 (66.7%) had a successful outcome in group 2 receiving voriconazole. There was significant difference between adverse reactions of the two drugs, with amphotericin B having a significant renal and cardiotoxicity as compared to voriconazole; though patients on voriconazole developed skin rashes which were transient and disappeared on completion of the therapy. Conclusion The present series demonstrates that oral voriconazole can be the primary line of therapy in chronic invasive sinus aspergillosis in carefully monitored immunocompetent cases. Multicentric, randomized studies are required to define disease definition, duration and successful outcome.

Pharmacokinetic and galactopoietic response to recombinant variants of bovine growth hormone

1993 ◽  
Vol 139 (3) ◽  
pp. 441-450 ◽  
Author(s):  
P. J. Eppard ◽  
T. C. White ◽  
B. K. Birmingham ◽  
R. L. Hintz ◽  
L. A. Bentle ◽  
...  
Keyword(s):  
Area Under The Curve ◽  
Latin Square ◽  
Central Compartment ◽  
Volume Of Distribution ◽  
Holstein Cows ◽  
Pharmacokinetic Parameters ◽  
Parameter Estimates ◽  
Concentration Data ◽  
Maximum Serum ◽  
Serum Gh

ABSTRACT Two studies were designed to examine the pharmacokinetic and galactopoietic potency of three molecular variants of recombinant-derived bovine GH (rbGH): [Met1, Leu127]-bGH, [Ala1, Val127]-bGH and [Ala1, Val127, His133]-bGH. Histidine substitution for arginine at residue 133 of rbGH was shown to impart thrombin resistance. In a Latin square design, nine lactating Holstein cows received a 25 mg rbGH bolus infusion via the jugular vein followed by frequent blood sampling over the next 12 h. The serum GH concentration data were found to fit to a two-compartment open model. Neither primary nor secondary kinetic parameter estimates differed significantly (P>0·05) among the three rbGH variants. Thus, the disposition of GH concentration at time t was described by the equation C(t)=(1295·5 μg/l) (e−(0·11/min)(t)) + (317·3 μg/l)(e−(0·03/min)(t)). Overall averages were: area under the curve=27·1 mg · min per 1, clearance=0·15 litres/min per 100 kg and volume of distribution of the central compartment =2·59 litres/100 kg. The t1/2 for the two compartments averaged 8·2 and 29·1 min. In the second study, 36 lactating Holstein cows received i.m. injections of one of four oil-based formulation treatments: control vehicle or 500 mg of one of the three rbGH variants every 14 days for 42 days. Average and maximum serum GH concentrations and area under the curve estimates were increased by approximately 3–6 μg/l, 5–15 μg/l and 40–90 μg · day per 1 respectively. Ala1, Val127 rbGH treatments elicited greater blood GH concentrations than [Met1, Leu127]-bGH when administered in an oil-based formulation. Blood GH responses did not directly translate into milk response differences, possibly due to differences in biopotency or receptor availability. Thrombin resistance resulting from substitution of histidine at position 127 of rbGH did not affect blood GH pharmacokinetic parameters or milk response over other rbGH variants. Journal of Endocrinology (1993) 139, 441–450

scholarly journals Population Pharmacokinetics of Liposomal Amphotericin B in Immunocompromised Children

2016 ◽  
pp. AAC.01427-16 ◽  
Author(s):  
Jodi M. Lestner ◽  
Andreas H. Groll ◽  
Ghaith Aljayyoussi ◽  
Nita L. Seibel ◽  
Aziza Shad ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
High Performance ◽  
Drug Exposure ◽  
Compartment Model ◽  
Invasive Fungal Disease ◽  
Volume Of Distribution ◽  
Liposomal Amphotericin B ◽  
Time Curve ◽  
Maximum Serum

BackgroundLiposomal amphotericin B (LAmB) is widely used in the treatment of invasive fungal disease (IFD) in adults and children. There are relatively limited PK data to inform optimal dosing in children that achieves systemic drug exposures comparable to those of adults.ObjectivesTo describe the pharmacokinetics of LAmB in children aged 1-17 years with suspected or documented IFD.MethodsThirty-five children were treated with LAmB at dosages of 2.5-10 mg kg-1daily. Samples were taken at baseline and at 0.5-2.0 hourly intervals for twenty-four hours after receipt of the first dose (n=35 patients) and on the final day of therapy (n=25 patients). LAmB was measured using high performance liquid chromatography (HPLC). The relationship between drug exposure and development of toxicity was explored.ResultsAn evolution in PK was observed during the course of therapy resulting in a proportion of patients (n=13) having significantly higher maximum serum concentration (Cmax) and area under the concentration time curve (AUC0-24) later in the course of therapy, without evidence of drug accumulation (Cminaccumulation ratio, AR < 1.2). The fit of a 2-compartment model incorporating weight and an exponential decay function describing volume of distribution best described the data. There was a statistically significant relationship between mean AUC0-24and probability of nephrotoxicity (OR 2.37; 95% CI 1.84-3.22, p=0.004).ConclusionsLAmB exhibits nonlinear pharmacokinetics. A third of children appear to experience a time-dependent change in PK, which is not explained by weight, maturation or observed clinical factors.

scholarly journals Pharmacokinetics and Safety of Oral Posaconazole in Neutropenic Stem Cell Transplant Recipients

2006 ◽  
Vol 50 (6) ◽  
pp. 1993-1999 ◽  
Author(s):  
Paul O. Gubbins ◽  
Gopal Krishna ◽  
Angela Sansone-Parsons ◽  
Scott R. Penzak ◽  
Li Dong ◽  
...  
Keyword(s):  
Stem Cell ◽  
Steady State ◽  
Maximum Plasma ◽  
Cell Transplant ◽  
Once Daily ◽  
Daily Group ◽  
Group Iii ◽  
Group I ◽  
Dosing Frequency ◽  
Group Ii

ABSTRACT The pharmacokinetics of posaconazole oral suspension in neutropenic patients undergoing high-dose chemotherapy and stem cell transplantation were evaluated, and the association of plasma posaconazole exposure with the presence and severity of oral mucositis was explored in this nonrandomized, open-label, parallel-group, multiple-dose pharmacokinetic study. Thirty patients were enrolled and received one of three regimens (group I, 200 mg once daily; group II, 400 mg once daily; group III, 200 mg four times daily) for the duration of neutropenia. The mean total exposure for day 1, as shown by the area under the concentration-time curve from 0 to 24 h (AUC0-24), was 1.96 mg · h/liter in group I and was 51% higher in group II and in group III. Increases in AUC0-24 and maximum plasma concentration (C max) in groups II and III were dose related. The AUC0-24 and C max values on day 1 were similar between groups II and III. There was interpatient variability of up to 68% in the pharmacokinetic values for our study population. Steady state was attained by days 5 to 6. Average steady-state plasma posaconazole trough values were 192, 219, and 414 ng/ml in groups I, II, and III, respectively. The AUC0-24 and apparent oral clearance increased by increasing dose and dosing frequency. Mucositis appeared to reduce exposure but did not significantly affect mean total posaconazole exposure (AUC and C max) at steady state (P = 0.1483). Moreover, this reduction could be overcome by increasing the total dose and dosing frequency. Posaconazole was safe and well tolerated.

scholarly journals HIGH INTENSITY INTERVAL TRAINING LEBIH MENINGKATKAN KAPASITAS AEROBIK DARIPADA LOW INTENSITY STEADY STATE PADA ATLET KARATE DOJO CAMPUHAN ASRI DI DENPASAR

2019 ◽  
Author(s):  
I Ketut Wedarthana Aditya Prana ◽  
I Putu Gede Adiatmika ◽  
Tjokorda Gde Bagus Mahadewa ◽  
Dewa Putu Sutjana ◽  
Ketut Tirtayasa ◽  
...  
Keyword(s):  
Steady State ◽  
Aerobic Capacity ◽  
High Intensity ◽  
Interval Training ◽  
Physical Endurance ◽  
High Intensity Interval Training ◽  
Low Intensity ◽  
Group I ◽  
Group Ii ◽  
High Intensity Interval

Decreased physical endurance impacts for human fitness. The occurrence of decline in activities that can make physical decline of heart and lung function and decreased metabolic system. This physical endurance is divided into two parts, namely general durability and muscular endurance. This research aims to know HIIT training further increase aerobic capacity than in training of LISS in Dojo Campuhan Asri Denpasar. Type of experimental research with the randomized pre-posttest control group design. Aerobic capacity is measuring by MFT (multistage fitnest test). The research subjects were male karate athletes between 7-12 years, totaling 16 people and divided into two different treatment groups. Group I was given training in High Intensity Interval Training with training based on maximum repetition and Group II was given Low Intensity Steady State training with training based on a maximum time of 60 minutes with frequency of exercise 3 times a week for 6 weeks in both group. The result of increased aerobic capacity between the two Groups before and after the training was tested with t-independent, with the significant value ? = 0.05. Average aerobic capacity in both Groups before training with the value P = 0.339 and after training with the value P = 0.001. It shows that the group I and group II both gave an improved effect (P < 0.05). But in group I better than the group II (p < 0.05). It was concluded that aerobic capacity in Group I and Group II had both increased. However, the High Intensity Interval Training Group training is better than the Low Intensity Steady State Training Group. High Intensity Interval Training suggested training is recommended for athletes training. Keywords: High Intensity Interval Training , HIIT , Low Intensity Steady State, LISS, Capacity Aerobic, Karate.

scholarly journals A Pharmacokinetic Study of Amphotericin B Lipid Complex Injection (Abelcet) in Patients with Definite or Probable Systemic Fungal Infections

2000 ◽  
Vol 44 (10) ◽  
pp. 2900-2902 ◽  
Author(s):  
Adedayo Adedoyin ◽  
Christine E. Swenson ◽  
Lois E. Bolcsak ◽  
Andrzej Hellmann ◽  
Danuta Radowska ◽  
...  
Keyword(s):  
Body Weight ◽  
Steady State ◽  
Amphotericin B ◽  
Fungal Infections ◽  
Volume Of Distribution ◽  
Lipid Complex ◽  
Systemic Fungal Infection ◽  
Elimination Half ◽  
Amphotericin B Lipid Complex ◽  
Pharmacokinetic Evaluation

ABSTRACT This study describes a pharmacokinetic evaluation of amphotericin B (AMB) lipid complex injection (ABLC or Abelcet) in 17 patients with systemic fungal infection administered 5 mg/kg of body weight/day by infusion for 10 to 17 days. The results showed that AMB exhibited multiexponential disposition with high clearance, large volume of distribution at steady state, and long apparent elimination half-life but no evidence of accumulation in the blood after multiple daily doses. The results confirm previous observations and further reinforce the suggestion that ABLC may exist as a depot in the tissues from which free AMB is slowly released to limit exposure.

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