scholarly journals Pharmacokinetics of Nikkomycin Z after Single Rising Oral Doses

2009 ◽  
Vol 53 (6) ◽  
pp. 2517-2521 ◽  
Author(s):  
David E. Nix ◽  
Robert R. Swezey ◽  
Richard Hector ◽  
John N. Galgiani
Keyword(s):  
High Performance ◽  
Relative Bioavailability ◽  
Time Curve ◽  
Chromatography Method ◽  
Blood Samples ◽  
Drug Concentrations ◽  
Nikkomycin Z ◽  
Group 2 ◽  
Liquid Chromatography Method ◽  
Oral Doses

ABSTRACT Nikkomycin Z is an antifungal drug that inhibits chitin synthase. This agent is under development as an orphan product for treatment of coccidioidomycosis. Safety and pharmacokinetics of nikkomycin Z were evaluated in healthy male subjects following single, rising oral doses ranging from 250 mg to 2,000 mg. A total of 12 subjects were recruited and divided into two groups. Group 1 (n = 6) received two out of three doses of 250 mg, 1,000 mg, or 1,750 mg and a placebo randomly in place of one of the doses. Group 2 (n = 6) received two out of three doses of 500 mg, 1,500 mg, or 2,000 mg and a placebo in place of one of the doses. Subjects were confined to the study unit overnight prior to dosing, and 12 blood samples were collected over 24 h postdosing while subjects were confined. Subjects returned for additional blood samples and safety evaluations at 48 h and 72 h after each dose. There was a 2-week washout period between doses. Plasma drug concentrations were determined using a validated high-performance liquid chromatography method. Nikkomycin Z was absorbed after oral administration, reaching a maximum concentration in serum of 2.21 μg/ml at 2 h postdose and an area under the concentration-time curve from 0 h to infinity of 11.3 μg·h/ml for the 250-mg dose. Pharmacokinetics appeared linear over the range of 250 to 500 mg; however, relative bioavailability was about 62 to 70% for the 1,000-mg dose and 42 to 47% for doses between 1,500 and 2,000 mg. The mean terminal half-life ranged from 2.1 to 2.5 h and was independent of dose. No serious or dose-related adverse events were observed. This study provides a basis for pharmacokinetic simulations and continued studies of nikkomycin Z administered in multiple doses.

scholarly journals Pharmacokinetics and Safety of Voriconazole following Intravenous- to Oral-Dose Escalation Regimens

2002 ◽  
Vol 46 (8) ◽  
pp. 2546-2553 ◽  
Author(s):  
L. Purkins ◽  
N. Wood ◽  
P. Ghahramani ◽  
K. Greenhalgh ◽  
M. J. Allen ◽  
...  
Keyword(s):  
Oral Dose ◽  
High Performance ◽  
Fold Increase ◽  
Study Cohort ◽  
Time Curve ◽  
Chromatography Method ◽  
Blood Samples ◽  
Mean Values ◽  
Matching Placebo ◽  
Oral Dosing

ABSTRACT In this study, the safety, tolerability, and pharmacokinetics of intravenous (i.v.)- to oral-dose regimens of voriconazole were evaluated with a group of 42 healthy men, 41 of whom completed the study. Two cohorts of subjects participated in the study. Cohort 1 (n = 28) took part in two study periods, each consisting of 14 days separated by a minimum 7-day washout. In one of the periods, 14 subjects received 6 mg/kg i.v. twice a day (b.i.d.) on day 1 followed by 3 mg/kg i.v. b.i.d. on days 2 to 7 and were then switched to 200 mg orally b.i.d. for days 8 to 14. In the other period, subjects received 6 mg/kg i.v. b.i.d. on day 1 followed by 5 mg/kg i.v. b.i.d. on days 2 to 7and were then switched to 400 mg orally b.i.d. for days 8 to 14. The remaining 14 subjects in cohort 1 received a matching placebo throughout the study. In cohort 2 (n = 14), 7 subjects received 6 mg/kg i.v. b.i.d. on day 1 followed by 4 mg/kg i.v. b.i.d. on days 2 to 7 and were then switched to 300 mg orally b.i.d. for days 8 to 14. The remaining seven subjects in cohort 2 received a matching placebo. Blood samples were taken prior to dosing on days 1 to 6 and on days 8 to 13. Blood samples were drawn prior to dosing and at frequent intervals up to 12 h following the morning dose on days 7 and 14 of each study period. The samples were assayed for voriconazole by a high-performance liquid chromatography method. The maximum concentration in plasma (C max) occurred at the end of the 1-h i.v. infusion and between 1.4 and 1.8 h after oral administration. Voriconazole exhibited nonlinear pharmacokinetics, possibly due to saturable metabolism. For cohort 1, both C max and the area under the concentration-time curve within a dosage interval (AUCτ) increased disproportionately with dose for both i.v. and oral dosing. For i.v. dosing, a 1.7-fold increase in dose resulted in 2.4- and 3.1-fold increases in C max and AUCτ, respectively. Similarly, a 2-fold increase in oral dosing resulted in 2.8- and 3.9-fold increases in C max and AUCτ, respectively. The mean values for C max observed following oral dosing were lower than those obtained after i.v. administration, ranging from 62.7 to 89.6% of the i.v. value. After the switch from i.v. to oral dosing, most subjects achieved steady state by day 4, and mean minimum concentrations in plasma remained above clinically important MICs. The pharmacokinetic profiles for saliva followed a pattern similar to those observed for plasma; there was a highly significant correlation between plasma and saliva voriconazole concentrations (P < 0.0001). Voriconazole was well tolerated; the most commonly reported adverse events in voriconazole-treated subjects were mild to moderate headache, rash, and abnormal vision. Visual function tests detected no further abnormalities during voriconazole treatment.

scholarly journals A Rapid Anion Exchange High-Performance Liquid Chromatography Method for the Measurement of HbA2 in Whole Blood

1996 ◽  
Vol 33 (3) ◽  
pp. 253-256 ◽  
Author(s):  
B G Keevil ◽  
P W Maylor ◽  
D Rowlands
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
Whole Blood ◽  
High Performance ◽  
Hplc Method ◽  
Chromatography Method ◽  
Blood Samples ◽  
Centrifugation Step ◽  
Liquid Chromatography Method ◽  
Good Agreement

We developed a binary gradient high-performance liquid chromatography (HPLC) method for measuring HbA2 in whole blood samples using a Pharmacia Mono Q column (1 mL) and measurement at 415 nm. The assay requires a simple lysis and centrifugation step before injection onto the column. We found good agreement of results between the HPLC method and the Helena column chromatography method. The within batch precision was 2·6% and between batch precision was 4·6%. We found that using 30 mM Tris buffers (pH 7·8) with a sodium chloride gradient resulted in short analysis times and good chromatographic separation of HbA2, HbS and HbA. We conclude that this is a robust assay for the diagnosis of β-thalassaemia.

Stability of calcium levofolinate, 5-fluorouracil and oxaliplatin (FOLFOX) mixture

2021 ◽  
pp. 107815522110208
Author(s):  
Chantal Al Sabbagh ◽  
Elena Agapova ◽  
Vincent Boudy ◽  
Nathalie Mignet
Keyword(s):  
Ternary Mixture ◽  
High Performance ◽  
Drug Stability ◽  
Pharmaceutical Products ◽  
Chromatography Method ◽  
Knowing That ◽  
Drug Concentrations ◽  
Ph Dependent ◽  
Liquid Chromatography Method ◽  
The Stability

FOLFOX is the most common chemotherapy combination prescribed in colorectal cancer. It is composed of calcium levofolinate, 5-fluorouracil and oxaliplatin which demonstrated synergistic outcome. Nowadays, the lack of all-in-one formulation is due to the chemical composition of the pharmaceutical products and the highly pH-dependent stability of each drug. Herein, we aimed to investigate the stability of a ternary mixture of 5-fluorouracil, oxaliplatin and calcium levofolinate, knowing that coadministering these drugs would improve their efficacy. The effect of three pHs (5.0, 6.0 and 7.5) and two drug concentrations (8/3/6 and 1/1/1 mg/ml for 5-fluorouracil, oxaliplatin and calcium levofolinate, respectively) were examined. A high-performance liquid chromatography method was developed to separate and quantify the three drugs in one run. At higher concentrations, the ternary mixture was unstable regardless of pH. By reducing concentration, drug stability and compatibility in the mixture was improved at pH 5.0 for up to 3 days at +5°C ± 3 °C. In addition, binary mixtures provided stable properties at defined pHs. 5-fluorouracil/oxaliplatin mixture was stable at pH 5.0 over 48 hours while 5-fluorouracil/calcium levofolinate mixture was stable at pHs 6.0 and 7.5 up to 7 days.

scholarly journals HPLC Quantification of Cytotoxic Compounds fromAspergillus niger

2017 ◽  
Vol 2017 ◽  
pp. 1-7
Author(s):  
Paula Karina S. Uchoa ◽  
Leandro Bezerra de Lima ◽  
Antonia T. A. Pimenta ◽  
Maria da Conceição F. de Oliveira ◽  
Jair Mafezoli ◽  
...  
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
Standard Deviation ◽  
High Performance ◽  
Chromatography Method ◽  
Relative Standard ◽  
Validation Parameters ◽  
Cytotoxic Compounds ◽  
Liquid Chromatography Method ◽  
Marine Strain

A high-performance liquid chromatography method was developed and validated for the quantification of the cytotoxic compounds produced by a marine strain ofAspergillus niger. The fungus was grown in malt peptone dextrose (MPD), potato dextrose yeast (PDY), and mannitol peptone yeast (MnPY) media during 7, 14, 21, and 28 days, and the natural products were identified by standard compounds. The validation parameters obtained were selectivity, linearity (coefficient of correlation > 0.99), precision (relative standard deviation below 5%), and accuracy (recovery > 96).

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