Pharmacokinetics of undiluted or diluted high-dose etoposide with or without busulfan administered to patients with hematologic malignancies.

1994 ◽  
Vol 12 (7) ◽  
pp. 1468-1474 ◽  
Author(s):  
K Mross ◽  
P Bewermeier ◽  
W Krüger ◽  
M Stockschläder ◽  
A Zander ◽  
...  
Keyword(s):  
High Performance ◽  
Drug Exposure ◽  
Area Under The Curve ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
High Dose ◽  
Pharmacokinetic Data ◽  
Blood Samples ◽  
Systemic Drug Exposure ◽  
Systemic Drug

PURPOSE We used two different methods to administer high-dose etoposide (VP-16) during a myeloablative conditioning chemotherapy regimen before bone marrow transplantation (BMT). VP-16 was administered either diluted (0.5 mg/mL) or undiluted (20 mg/mL), with or without busulfan. PATIENTS AND METHODS Blood samples were drawn from 17 patients during the infusion (6 hours) and thereafter daily until 2 days after BMT. VP-16 concentrations were measured in all plasma samples by high-performance liquid chromatography (HPLC) and electrochemical detection, and the results were analyzed with a pharmacokinetic data analysis system. RESULTS All calculated pharmacokinetic parameters in the two patient groups (VP-16 administered diluted or undiluted) were similar. There were no statistically significant differences in half-lives, mean residence time (MRT), volume of distribution, total clearance, or area under the curve (AUC). VP-16 was found in blood samples from eight of 17 patients at the time of BMT. Significant differences in systemic drug exposure and systemic clearance were found when patients were grouped according to treatment with busulfan or with total-body irradiation (TBI). CONCLUSION The two administration modes for VP-16, either diluted or undiluted, are bioequivalent in pharmacokinetic terms. The terminal half-lives were longer than expected and resulted in significant VP-16 plasma levels at the time of BMT. The biologic significance remains unclear. Busulfan and/or concomitant medication with phenytoin influence plasma clearance (clp) and systemic drug exposure significantly.

scholarly journals Compartmental Pharmacokinetics of the Antifungal Echinocandin Caspofungin (MK-0991) in Rabbits

2001 ◽  
Vol 45 (2) ◽  
pp. 596-600 ◽  
Author(s):  
Andreas H. Groll ◽  
Bryan M. Gullick ◽  
Ruta Petraitiene ◽  
Vidmantas Petraitis ◽  
Myrna Candelario ◽  
...  
Keyword(s):  
High Performance ◽  
Pharmacokinetic Model ◽  
Area Under The Curve ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Chromatography Method ◽  
Opportunistic Fungi ◽  
The Mean ◽  
Liquid Chromatography Method

ABSTRACT The pharmacokinetics of the antifungal echinocandin-lipopeptide caspofungin (MK-0991) in plasma were studied in groups of three healthy rabbits after single and multiple daily intravenous administration of doses of 1, 3, and 6 mg/kg of body weight. Concentrations were measured by a validated high-performance liquid chromatography method and fitted into a three-compartment open pharmacokinetic model. Across the investigated dosage range, caspofungin displayed dose-independent pharmacokinetics. Following administration over 7 days, the mean peak concentration in plasma (C max) ± standard error of the mean increased from 16.01 ± 0.61 μg/ml at the 1-mg/kg dose to 105.52 ± 8.92 μg/ml at the 6-mg/kg dose; the mean area under the curve from 0 h to infinity rose from 13.15 ± 2.37 to 158.43 ± 15.58 μg · h/ml, respectively. The mean apparent volume of distribution at steady state (Vdss) was 0.299 ± 0.011 liter/kg at the 1-mg/kg dose and 0.351 ± 0.016 liter/kg at the 6-mg/kg dose (not significant [NS]). Clearance (CL) ranged from 0.086 ± 0.017 liter/kg/h at the 1-mg/kg dose to 0.043 ± 0.004 liter/kg/h at the 6-mg/kg dose (NS), and the mean terminal half-life was between 30 and 34 h (NS). Except for a trend towards an increasedVdss, there were no significant differences in pharmacokinetic parameters in comparison to those after single-dose administration. Caspofungin was well tolerated, displayed linear pharmacokinetics that fit into a three-compartment pharmacokinetic model, and achieved sustained concentrations in plasma that were multiple times in excess of reported MICs for susceptible opportunistic fungi.

scholarly journals Pharmacokinetic and bioavailability study of lercanidipine hydrochloride fast disintegrating tablets in rabbits by high-performance liquid chromatography

2020 ◽  
Vol 11 (4) ◽  
pp. 7289-7292
Author(s):  
Seema Saini ◽  
Rajeev Garg
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
Plasma Concentration ◽  
High Performance ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Data ◽  
Blood Samples ◽  
Fast Disintegrating Tablet ◽  
Fast Disintegrating Tablets ◽  
Lercanidipine Hydrochloride

In the present study, fast disintegrating tablets of Lercanidipine Hydrochloride (LFDT) were tested in vivo in the buccal cavity of the rabbits. Various pharmacokinetic parameters were analysed in the study, including maximum measured plasma concentration (Cmax), time of maximum measured plasma concentration (tmax) and area under the plasma concentration vs time curve (AUC). Also, the comparative study of the Lercanidipine Hydrochloride fast disintegrating tablets (LFDT) was performed with the marketed conventional tablets of the drug (LMKT). The technique selected for the bioanalytical analysis of the blood samples of the rabbits for pharmacokinetic data computation was High-Performance Liquid Chromatography. An already well-established and validated method was used to analyse the blood samples of the rabbits. The results revealed that the rate of absorption was improved for fast disintegrating tablets of Lercanidipine Hydrochloride (LFDT) as compared to the marketed conventional tablets of the drug (LMKT). This indicated that drug was rapidly absorbed from the fast disintegrating tablet and attained elevated plasma concentration in a short interval after dosing than the marketed formulation. However, the value of tmax was drastically shorter for LFDT than the LMKT. The average peak plasma concentration also designated a rise in the extent of absorption (AUC). From the present study, it was concluded that the fast disintegrating tablet batch (LFDT) had much more improved pharmacokinetic parameters as compared to its conventional marketed counterpart (LMKT).

Methotrexate pharmacokinetics and prognosis in osteosarcoma.

1994 ◽  
Vol 12 (7) ◽  
pp. 1443-1451 ◽  
Author(s):  
N Graf ◽  
K Winkler ◽  
M Betlemovic ◽  
N Fuchs ◽  
U Bode
Keyword(s):  
Area Under The Curve ◽  
Disease Free Survival ◽  
Peak Level ◽  
Drug Regimen ◽  
Fixed Dose ◽  
Pharmacokinetic Parameters ◽  
High Dose ◽  
Pharmacokinetic Data ◽  
Full Effect ◽  
Peak Value

PURPOSE The influence of methotrexate (MTX) pharmacokinetic parameters on the efficacy of high-dose MTX (HDMTX) in osteosarcoma was analyzed. PATIENTS AND METHODS MTX serum peak values from 198 patients in 1,703 treatment courses and more detailed pharmacokinetic data from 185 patients in 1,045 treatment courses from the Cooperative Osteosarcoma Study Group (COSS) studies COSS-80, COSS-82, and COSS-86 were investigated. RESULTS A mean threshold peak level of > or = 1,000 mumol/L for the repeated MTX courses of individual patients was found to correlate significantly to prognosis in study COSS-80 (18% v 64% actuarial 10-year disease-free survival [DFS], P = .0001). Six courses of HDMTX per patient who achieved peak values > or = 1,000 mumol/L were found to be sufficient for a full effect to be seen in DFS in COSS-80. The MTX peak level was found to correlate closely to the area under the curve (AUC). However, AUC was a less powerful determinator of prognosis than the mean threshold MTX peak value. In patients who received cisplatin (DDP) as one of the additional drugs to MTX, the peak values and AUC were significantly increased (1,396 v 1,276 mumol/L, P = .011; 6,684 v 5,820 h.mumol/L, P < or = .002) and only a few patients (6%) did not achieve mean threshold MTX peak values. In addition, following restriction of hydration fluid after the MTX infusion from 4.5 to 3.0 L/m2 per 24 hours, the early MTX half-life (t1/2) and the AUC, but not the MTX peak value, were significantly increased (3.4 v 3.05 hours, and 6,760 v 5,998 h.mumol/L, respectively, P < or = .002). CONCLUSION MTX pharmacokinetics significantly influence the efficacy of MTX in osteosarcoma. Individual adaptation of the MTX dose to ensure a threshold peak serum level > or = 1,000 mumol/L does not seem necessary at a fixed dose of 12 g MTX/m2, restriction of hydration fluid to 3 L/m2 per 24 hours, and concomitant use of DDP within the drug regimen.

scholarly journals Comparative Plasma Pharmacokinetics of Ceftriaxone and Ertapenem in Normoalbuminemia, Hypoalbuminemia, and Albumin Replacement in a Sheep Model

2020 ◽  
Vol 64 (7) ◽  
Author(s):  
Jayesh A. Dhanani ◽  
Benjamin Ahern ◽  
Liad Lupinsky ◽  
Karen Jackson ◽  
Steven C. Wallis ◽  
...  
Keyword(s):  
Drug Exposure ◽  
Area Under The Curve ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
The Other ◽  
Terminal Phase ◽  
Pharmacokinetic Parameters ◽  
Sheep Model ◽  
Drug Concentrations ◽  
Ultrahigh Performance Liquid Chromatography

ABSTRACT Optimal concentrations of unbound antimicrobials are essential for a maximum microbiological effect. Although hypoalbuminemia and albumin fluid resuscitation are common in critical care, the effects of different albumin concentrations on the unbound concentrations of highly protein-bound antimicrobials are not known. The aim of this study was to compare the effects of different albumin states on total and unbound concentrations of ertapenem and ceftriaxone using an ovine model. The study design was a prospective, three-phase intervention observational study. The subjects were healthy Merino sheep. Eight sheep were subjected to three experimental phases: normoalbuminemia, hypoalbuminemia using plasmapheresis, and albumin replacement using a 25% albumin solution. In each phase, ceftriaxone at 40 mg/kg of body weight and ertapenem at 15 mg/kg were given intravenously. Blood samples were collected at predefined intervals and analyzed using an ultrahigh-performance liquid chromatography–tandem mass spectrometry method. Pharmacokinetic parameters such as the area under the curve from 0 to 24 h (AUC0–24), plasma clearance (CL), and apparent volume of distribution in the terminal phase (V) were estimated and compared between the phases. The protein and albumin concentrations were significantly different between phases. Hypoalbuminemia resulted in a significantly lower AUC0–24 and higher CL of total and unbound concentrations of ceftriaxone than in the other phases, whereas albumin replacement led to higher AUC0–24 and lower CL than in the other phases for both drugs. The V values for total drug concentrations for both drugs were significantly lower with albumin replacement. For highly protein-bound drugs such as ceftriaxone and ertapenem, both hypoalbuminemia and albumin replacement may affect unbound drug exposure.

scholarly journals Influence of Energy Drinks on Pharmacokinetic Parameters of Sildenafil in Rats

2018 ◽  
Vol 11 (3) ◽  
pp. 1317-1328
Author(s):  
Mohammad Abdulla ◽  
Eyad Mallah ◽  
Wael Abu Dayyih ◽  
Walid Abu Rayyan ◽  
Feras Darwish El-Hajji ◽  
...  
Keyword(s):  
Plasma Level ◽  
High Performance ◽  
Research Work ◽  
Area Under The Curve ◽  
Ultra Violet ◽  
Energy Drinks ◽  
Accurate Method ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Data ◽  
Red Bull

Both sildenafil and RED BULL®(energy drink) are claimed to boost up energy.RED BULL®, one of the most commonly used energy drinks and its easily and widely available for daily use, the idea of this research work had arisen from observations about the concomitant use of sildenafil with RED BULL® by men seeking for better sexual performance. To study the effect of RED BULL® on the pharmacokinetic profile of sildenafil by using HPLC.The pharmacokinetic parameters (Cmax, Tmax and AUC) were determined in 10 rats following oral administration of 0.57 mg/ml sildenafil with and without RED BULL® in crossover design, to achieve this purpose,simple, rapid and accurate method for validation and determination of sildenafil in rat plasma in the presence of RED BULL® has been developed. This was performed using High-Performance Liquid Chromatography- Ultra Violet (HPLC-UV). The pharmacokinetic data showed that sildenafil plasma level was lower when combined with RED BULL® According to the results obtained, maximum concentration (Cmax) for sildenafil alone was (162.05 ng/ml) after 0.5 hours of administration. The Cmax decreased to (44.68 ng/ml) after 0.5 hoursof administration RED BULL® concomitantly with sildenafil which showed a significant effect on sildenafil plasma level (P<0.001). The area under the curve (AUC) decreased significantly from (370.53 ng/ml*hr) for sildenafil alone to (87.74 ng/ml*hr) when combined with RED BULL®. RED BULL® can alter sildenafil pharmacokinetic if they were taken together.

scholarly journals Moxifloxacin Pharmacokinetics and Pleural Fluid Penetration in Patients with Pleural Effusion

2013 ◽  
Vol 58 (3) ◽  
pp. 1315-1319 ◽  
Author(s):  
Kalliopi Chatzika ◽  
Katerina Manika ◽  
Paschalina Kontou ◽  
Georgia Pitsiou ◽  
Despina Papakosta ◽  
...  
Keyword(s):  
Pleural Effusion ◽  
Pleural Fluid ◽  
High Performance ◽  
Drug Exposure ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Time Interval ◽  
Parapneumonic Effusion ◽  
Malignant Effusion ◽  
Time Curve

ABSTRACTThe aim of this study was to evaluate the pharmacokinetics and penetration of moxifloxacin (MXF) in patients with various types of pleural effusion. Twelve patients with empyema/parapneumonic effusion (PPE) and 12 patients with malignant pleural effusion were enrolled in the study. A single-dose pharmacokinetic study was performed after intravenous administration of 400 mg MXF. Serial plasma (PL) and pleural fluid (PF) samples were collected during a 24-h time interval after drug administration. The MXF concentration in PL and PF was determined by high-performance liquid chromatography, and main pharmacokinetic parameters were estimated. Penetration of MXF in PF was determined by the ratio of the area under the concentration-time curve from time zero to 24 h (AUC24) in PF (AUC24PF) to the AUC24in PL. No statistically significant differences in the pharmacokinetics in PL were observed between the two groups, despite the large interindividual variability in the volume of distribution, clearance, and elimination half-life. The maximum concentration in PF (CmaxPF) in patients with empyema/PPE was 2.23 ± 1.31 mg/liter, and it was detected 7.50 ± 2.39 h after the initiation of the infusion. In patients with malignant effusion, CmaxPFwas 2.96 ± 1.45 mg/liter, but it was observed significantly earlier, at 3.58 ± 1.38 h (P< 0.001). Both groups revealed similar values of AUC24PF(31.83 ± 23.52 versus 32.81 ± 12.66 mg · h/liter). Penetration of MXF into PF was similarly good in both patient groups (1.11 ± 0.74 versus 1.17 ± 0.39). Despite similar plasma pharmacokinetics, patients with empyema/parapneumonic effusion showed a significant delay in achievement of PF maximum MXF levels compared to those with malignant effusion. However, in both groups, the degree of MXF PF penetration and the on-site drug exposure, expressed by AUC24PF, did not differ according to the type of pleural effusion.

scholarly journals Additional benefit of higher dose green tea in lowering postprandial blood glucose

2015 ◽  
Vol 24 (2) ◽  
pp. 97-102 ◽  
Author(s):  
Rita Lahirin ◽  
Inge Permadhi ◽  
Ninik Mudjihatini ◽  
Rahmawaty Ridwan ◽  
Ray Sugianto
Keyword(s):  
Blood Glucose ◽  
Green Tea ◽  
High Performance ◽  
Glucose Transporter ◽  
Area Under The Curve ◽  
Additional Benefit ◽  
Postprandial Blood Glucose ◽  
High Dose ◽  
Inhibitory Effects ◽  
Sodium Dependent

Background: Green tea contains catechins that have inhibitory effects on amylase, sucrase, and sodium-dependent glucose transporter (SGLT) which result in lowering of postprandial blood glucose (PBG). This beneficial effect has been widely demonstrated using the usual dose (UD) of green tea preparation. Our study was aimed to explore futher lowering of PBG using high dose (HD) of green tea in healthy adolescents. Methods: 24 subjects received 100 mL infusion of either 0.67 or 3.33 grams of green tea with test meal. Fasting, PBG at 30, 60, 120 minutes were measured. Subjects were cross-overed after wash out. PBG and its incremental area under the curve (IAUC) difference between groups were analyzed with paired T-test. Cathecin contents of tea were measured using high-performance liquid chromatography (HPLC). Results: The PBG of HD group was lower compared to UD (at 60 minutes =113.70 ± 13.20 vs 124.16 ± 8.17 mg/dL, p = 0.005; at 120 minutes = 88.95 ± 6.13 vs 105.25 ± 13.85 mg/dL, p < 0.001). The IAUC of HD was also found to be lower compared to UD (2055.0 vs 3411.9 min.mg/dL, p < 0.001). Conclusion: Additional benefit of lowering PBG can be achieved by using higher dose of green tea. This study recommends preparing higher dose of green tea drinks for better control of PBG.

scholarly journals Pharmacokinetics of danofloxacin in African catfish (Clarias gariepinus) after intravenous and intramuscular administrations

2019 ◽  
Vol 67 (4) ◽  
pp. 602-609
Author(s):  
Mohamed Aboubakr ◽  
Ahmed Soliman
Keyword(s):  
Bacterial Infections ◽  
High Performance ◽  
Clarias Gariepinus ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
African Catfish ◽  
Caudal Vein ◽  
Group 2 ◽  
Total Body ◽  
The Right

The plasma pharmacokinetics of danofloxacin was studied in healthy African catfish (Clarias gariepinus) following a single intravenous (IV) and intramuscular (IM) administration of 10 mg/kg at 22 °C. Catfish were divided into two groups (each group containing 78 fish), then danofloxacin mesylate (10 mg/kg) was administered IV (into the caudal vein) in Group 1 and IM (into the right epaxial muscle) in Group 2, and blood was obtained from the caudal vein before (0 h) and after (0.25, 0.5, 1, 2, 4, 8, 12, 24, 36, 48, 72 and 96 h) of drug administration. High-performance liquid chromatography was used for the determination of plasma concentration, and a non-compartmental model was used for the analysis of pharmacokinetic parameters. After IV administration, elimination half-life (t1/2λz, 24.49 h), mean residence time (MRT, 30.14 h), volume of distribution at steady state (Vdss, 1.07 L/kg) and total body clearance (CLT, 0.035 L/h/kg) were determined. After IM administration, t1/2λz, MRT, peak concentration (Cmax), time to reach Cmax and bioavailability were 47.64 h, 61.06 h, 5.22 µg/mL, 1 h and 67.12%, respectively. After IM administration, danofloxacin showed good bioavailability and long t1/2λz. The favourable pharmacokinetic characteristics after IM administration support the use of danofloxacin for the treatment of susceptible bacterial infections in catfish.

scholarly journals Intrathecal Riluzole for the Treatment of Patients With Amyotrophic Lateral Sclerosis

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Nicholas M Boulis
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Side Effects ◽  
Oral Administration ◽  
Oral Therapy ◽  
Drug Exposure ◽  
Oral Treatment ◽  
Oral Drug ◽  
Systemic Drug Exposure ◽  
Lateral Sclerosis ◽  
Systemic Drug

Abstract INTRODUCTION Oral riluzole is the only approved treatment known to improve survival in patients with amyotrophic lateral sclerosis (ALS), with modest efficacy and dosing limited by hepatic toxicity and asthenia. We postulated that a continuous intrathecal (IT) delivery of low daily doses of riluzole could elevate spinal cord (SC) concentrations well above those achievable with oral treatment alone, without increasing side-effects. METHODS A 6-wk and a 24-wk GLP study were conducted to evaluate the safety of IT riluzole in purpose-bred hound dogs. Oral riluzole, equivalent to 50 mg BID in humans, was administered in combination with one of 3 IT doses given through continuous infusion. Plasma, SC, and brain concentrations of riluzole were measured, along with assessments of safety and tolerability. RESULTS In the 6-wk study, when combining the oral and IT routes, IT infusion significantly increased SC concentrations well above those achieved with oral drug administration alone, without increasing brain concentrations. All IT doses in combination with oral administration were well tolerated by the animals. In the 6-mo study, the lowest dose used in the 6-wk study was dropped and a higher dose was added. This highest dose of IT riluzole was not tolerated by the dogs and yielded SC and brain concentrations significantly higher than achieved in any of our previous studies. CONCLUSION Continuous IT administration of riluzole when combined with oral administration can increase the SC concentration of riluzole above those achievable with oral therapy, without increasing the risk for adverse events associated with systemic drug exposure or off-target side-effects in the brain. Therefore, IT riluzole infusion when used in conjunction with oral therapy may safely enhance lower motor neuron neuroprotection and improve the survival benefit of the drug through enhanced SC delivery, and, with a careful selection of IT doses, it could be implemented in patients with ALS.

High-dose cisplatin with sodium thiosulfate protection.

1985 ◽  
Vol 3 (2) ◽  
pp. 237-244 ◽  
Author(s):  
C E Pfeifle ◽  
S B Howell ◽  
R D Felthouse ◽  
T B Woliver ◽  
P A Andrews ◽  
...  
Keyword(s):  
Renal Damage ◽  
Drug Exposure ◽  
Elimination Rate ◽  
Sodium Thiosulfate ◽  
Volume Of Distribution ◽  
High Dose ◽  
Concurrent Administration ◽  
Neutralizing Agent ◽  
Total Body ◽  
Body Clearance

Nephrotoxicity frequently limits the dose of cisplatin to less than 120 mg/m2 per injection. Sodium thiosulfate is a neutralizing agent for cisplatin that protects against renal damage. To determine whether injection of thiosulfate would permit larger doses of cisplatin to be administered, a fixed 9.9-g/m2 dose of thiosulfate was given intravenously over three hours concurrently with escalating doses of cisplatin. Cisplatin was administered over the last two hours of the thiosulfate infusion. Using this technique, it was possible to escalate the cisplatin dose to 225 mg/m2 before dose-limiting toxicities were encountered. Comparison of cisplatin pharmacokinetics in patients treated with 202.5 mg/m2 plus thiosulfate to those in patients treated with 100 mg/m2 without thiosulfate indicated that there were no changes in the elimination rate constant, volume of distribution, or total body clearance of cisplatin. The total drug exposure for the plasma was approximately twofold at the higher cisplatin dose. This study demonstrates that concurrent administration of thiosulfate permits at least a twofold increase in dose and total exposure to cisplatin.

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