A study of the pharmacokinetics of moxifloxacin by the dynamics of its distribution in the blood plasma and saliva of healthy volunteers: a comparative analysis and possible extrapolation methods

AbstractObjectivesThe pharmacokinetics of moxifloxacin in plasma and saliva was investigated in this study.MethodsThe pharmacokinetics of two specialty drugs of moxifloxacin – reference (Ref) and test (Test) preparation – was studied in 18 healthy volunteers after a single oral dose of 400 mg.ResultsIt was found that the concentration of moxifloxacin in saliva 3–24 h after taking the drugs was statistically significantly higher than that in plasma. A high correlation was observed between the concentration of moxifloxacin in plasma and saliva of volunteers after taking of Ref and Test. Some pharmacokinetic parameters, calculated by the concentration of moxifloxacin in saliva and plasma, are statistically different. A technique is proposed for extrapolating the concentration of moxifloxacin in plasma according to its concentration in saliva using the established linear relationship between the moxifloxacin in plasma and saliva of volunteers in time interval of 3–24 h after taking Ref. Based on the obtained extrapolated concentration of moxifloxacin, the pharmacokinetic parameters were calculated for two studied drugs and did not statistically differ from the parameters calculated according to the data in plasma.ConclusionsThe developed method of concentration extrapolation allows the use of saliva for pharmacokinetic studies of the tablet preparations of moxifloxacin.

Download Full-text

BIOANALYTICAL METHOD DEVELOPMENT AND VALIDATION OF MICRONIZED GLICLAZIDE IN HUMAN PLASMA BY LC-MS/MS AND ITS PHARMACOKINETIC STUDIES

INDIAN DRUGS ◽

10.53879/id.55.09.11405 ◽

2018 ◽

Vol 55 (09) ◽

pp. 24-33

Author(s):

R. Bose ◽

◽

S Dan ◽

P. Mandal ◽

P. Sarkar ◽

...

Keyword(s):

Single Dose ◽

Oral Bioavailability ◽

Method Development ◽

Test Preparation ◽

Pharmacokinetic Parameters ◽

Pharmacokinetic Studies ◽

Particle Size Reduction ◽

Male Adult ◽

Minimum Effective Concentration ◽

Reference Preparation

Drugs having poor oral bioavailability, fail to reach the minimum effective concentration required to achieve pharmacological action. Improvement of the oral bioavailability of the drug is the most realistic approach, as it is the most preferred and convenient route of administration. Besides numerous techniques to improve oral bioavailability of the drugs, particle size reduction leads to increase in the effective surface area, resulting in enhancement of solubility and dissolution velocity of the drug. In the present study a sustained release tablet formulation containing 60mg micronized gliclazide was attempted to develop and a randomized, two period, two treatment crossover, single dose, pilot study of test preparation along with a marketed sample of Gliclazide 60mg was carried out on 6 healthy male, adult, human volunteers under fasting condition to establish the bioequivalence of the new formulation with a washout period of one week. The developed method was found to be simple, reproducible, sensitive, and specific for the determination of gliclazide from plasma and was also applied to study the pharmacokinetic parameters of gliclazide. The mean peak plasma levels of gliclazide with the reference preparation on the study day ranged between 2562.27–2823.61ng/mL, while the test preparation ranged between 3091.24–3467.66ng/mL. On the basis of comparison of the AUC0-t for gliclazide after single dose administration, the relative bioavailability of the test preparation was 109.96% of that of the reference preparation.

Download Full-text

Evaluation of Pharmacokinetic Parameters of Cibenzoline after Administration of a Single Oral Dose in Healthy Volunteers.

Iryo Yakugaku (Japanese Journal of Pharmaceutical Health Care and Sciences) ◽

10.5649/jjphcs.27.375 ◽

2001 ◽

Vol 27 (4) ◽

pp. 375-379

Author(s):

Masahiko Obayashi ◽

Yoshiaki Matsumoto ◽

Kayoko Hashimoto ◽

Takayoshi Kosugi ◽

Minoru Kurokawa ◽

...

Keyword(s):

Oral Dose ◽

Healthy Volunteers ◽

Single Oral Dose ◽

Pharmacokinetic Parameters

Download Full-text

Pharmacokinetics of diltiazem hydrochloride delay-onset sustained-release pellet capsules in healthy volunteers

Brazilian Journal of Pharmaceutical Sciences ◽

10.1590/s1984-82502013000100004 ◽

2013 ◽

Vol 49 (1) ◽

pp. 29-38 ◽

Cited By ~ 2

Author(s):

Xi-Qing Yan ◽

Zhi-Gang Chen ◽

Rong-Liang Wang ◽

Jun Yang ◽

Fang Ai ◽

...

Keyword(s):

Controlled Release ◽

Oral Dose ◽

Sustained Release ◽

Healthy Volunteers ◽

Single Oral Dose ◽

High Performance ◽

Reversed Phase ◽

Pharmacokinetic Parameters ◽

Diltiazem Hydrochloride ◽

New Formulation

The pharmacokinetics (PK) of ordinary tablets and sustained release capsules of diltiazem hydrochloride in human clinical trials had been studied. The PK of diltiazem hydrochloride delay-onset sustained-release pellet capsules, a new dosage form, has not been reported, although it is very important to clinical use. In this paper, we investigated the PK of diltiazem hydrochloride delay-onset sustained-release pellet capsules and the food influence in Chinese healthy volunteers. The PK parameters indicated that the diltiazem hydrochloride delay-onset sustained-release pellet capsules appeared marked characteristics of delayed and controlled release. An opened-label, randomized and parallel clinical trial was conducted in 36 Chinese healthy volunteers with single oral dose (90 mg, 180 mg or 270 mg) and a multiple oral dose (90 mg d-1×6 d) administration. The effect of food on the PK of one single oral dose (360 mg) was investigated in 24 healthy Chinese volunteers. Plasma diltiazem concentration was determined by reversed-phase high-performance liquid chromatography (RP-HPLC) and the main pharmacokinetic parameters were analyzed by PKSolver (Ver 2.0). All clinical studies were conducted in the Clinical Pharmacological Center (No. JDX1999064) of Xiangya Hospital Affiliated Central South University, China. The PK parameters suggested that the new formulation had marked characteristics of delayed and controlled release of diltiazem, and food intake did not alter significantly diltiazem pharmacokinetic parameters.

Download Full-text

A Multicenter Study of Recombinant Factor VIII (RecombinateTM) in Previously Treated Patients with Hemophilia A

Thrombosis and Haemostasis ◽

10.1055/s-0038-1656030 ◽

1997 ◽

Vol 77 (04) ◽

pp. 660-667 ◽

Cited By ~ 110

Author(s):

G C White ◽

S Courter ◽

G L Bray ◽

M Lee ◽

E D Gomperts ◽

...

Keyword(s):

Hemophilia A ◽

Recombinant Dna ◽

Home Treatment ◽

Pharmacokinetic Parameters ◽

Pharmacokinetic Studies ◽

Open Label ◽

Treat Ment ◽

Previously Treated Patients ◽

Bleeding Episodes

SummaryA prospective, open-label multicenter investigation has been conducted to compare pharmacokinetic parameters of recombinant DNA-derived FVIII (rFVIII) and plasma-derived FVIII concentrate (pdFVIII) and to assess safety and efficacy of long-term home-treat- ment with rFVIII for subjects with hemophilia A. Following comparative in vivo pharmacokinetic studies, 69 patients with severe (n = 67) or moderate (n = 2) hemophilia A commenced a program of home treatment using rFVIII exclusively for prophylaxis and treatment of all bleeding episodes for a period of 1.0 to 5.7 years (median 3.7 years). The mean in vivo half-lives of rFVIII and pdFVIII were both 14.7 h. In vivo incremental recoveries at baseline were 2.40%/IU/kg and 2.47%/IU/kg, respectively (p = 0.59). The response to home treatment with rFVIII was categorized as good or excellent in 3,195 (91.2%) of 3,481 evaluated bleeding episodes. Thirteen patients received rFVIII for prophylaxis for twenty-four surgical procedures. In all cases, hemostasis was excellent. Adverse reactions were observed in only 13 of 13,591 (0.096%) infusions of rFVIII; none was serious. No patient developed an inhibitor to r FVIII.

Download Full-text

Faculty Opinions recommendation of Decreased [18F]MPPF binding potential in the dorsal raphe nucleus after a single oral dose of fluoxetine: a positron-emission tomography study in healthy volunteers.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1115675.571742 ◽

2008 ◽

Author(s):

Ahmad Hariri ◽

Patrick Fisher

Keyword(s):

Positron Emission Tomography ◽

Oral Dose ◽

Healthy Volunteers ◽

Single Oral Dose ◽

Dorsal Raphe Nucleus ◽

Raphe Nucleus ◽

Emission Tomography ◽

Positron Emission Tomography Study ◽

Binding Potential ◽

Positron Emission

Download Full-text

Liquid Chromatography-Tandem Mass Spectrometry Method for Ticagrelor and its Active Metabolite Determination in Human Plasma: Application to a Pharmacokinetic Study

Current Analytical Chemistry ◽

10.2174/1573411015666190220144904 ◽

2020 ◽

Vol 16 (5) ◽

pp. 602-608

Author(s):

Niloufar Marsousi ◽

Serge Rudaz ◽

Jules A. Desmeules ◽

Youssef Daali

Keyword(s):

Clinical Trial ◽

Formic Acid ◽

Human Plasma ◽

Active Metabolite ◽

Pharmacokinetic Parameters ◽

Pharmacokinetic Studies ◽

Healthy Male ◽

Coronary Syndrome ◽

Healthy Male Volunteers ◽

Male Volunteers

Background: Ticagrelor is a highly recommended new antiplatelet agent for the treatment of patients with acute coronary syndrome at moderate or high ischemic risk. There is a real need for rapid and accurate analytical methods for ticagrelor determination in biological fluids for pharmacokinetic studies. In this study, a sensitive and specific LC-MS method was developed and validated for quantification of ticagrelor and its Active Metabolite (AM) in human plasma over expected clinical concentrations. Methods: Samples were handled by Liquid-Liquid Extraction (LLE). A linear gradient was applied with a mobile phase composed of formic acid 0.1% and acetonitrile with 0.1% of formic acid using a C18 reversed-phase column. MS spectra were obtained by electrospray ionization in negative mode and optimized at 521.4→360.9 m/z, 477.2→361.2 m/z and 528.1→367.9 m/z transitions for ticagrelor, AM and ticagrelor-d7, respectively. Results: This method allowed rapid elution, in less than 4 minutes, and quantification of concentrations as low as 2 ng/mL for ticagrelor and 1 ng/mL for AM using only 100 μL of human plasma. LLE using hexane/ethyl acetate (50/50) was an optimal compromise in terms of extraction recovery and endogenous compounds interference. Trueness values of 87.8% and 89.5% and precisions of 84.1% and 93.8% were obtained for ticagrelor and AM, respectively. Finally, the usefulness of the method was assessed in a clinical trial where a single 180 mg ticagrelor was orally administered to healthy male volunteers. Pharmacokinetic parameters of ticagrelor and its active metabolite were successfully determined. Conclusion: A sensitive and specific quantification LC-MS-MS method was developed and validated for ticagrelor and its active metabolite determination in human plasma. The method was successfully applied to a clinical trial where a single ticagrelor 180 mg dose was orally administered to healthy male volunteers. The described method allows quantification of concentrations as low as 2 ng/mL of ticagrelor and 1 ng/mL of the metabolite using only 100 μL of plasma.

Download Full-text

8806 Russian patients demonstrate T cell count as better marker of COVID-19 clinical course severity than SARS-CoV-2 viral load

Scientific Reports ◽

10.1038/s41598-021-88714-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Konstantin S. Sharov

Keyword(s):

Viral Load ◽

Comparative Analysis ◽

T Cell ◽

Cell Count ◽

T Lymphocyte ◽

Clinical Course ◽

Time Interval ◽

Early Prediction ◽

Disease Prognosis ◽

Respiratory Index

AbstractThe article presents a comparative analysis of SARS-CoV-2 viral load (VL), T lymphocyte count and respiratory index PaO2:FiO2 ratio as prospective markers of COVID-19 course severity and prognosis. 8806 patients and asymptomatic carriers were investigated in time interval 15 March–19 December 2020. T cell count demonstrated better applicability as a marker of aggravating COVID-19 clinical course and unfavourable disease prognosis than SARS-CoV-2 VL or PaO2:FiO2 ratio taken alone. Using T cell count in clinical practice may provide an opportunity of early prediction of deteriorating a patient’s state.

Download Full-text

Urinary Excretion and Bactericidal Activities of a Single Oral Dose of 400 Milligrams of Fleroxacin versus a Single Oral Dose of 800 Milligrams of Pefloxacin in Healthy Volunteers

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.42.7.1659 ◽

1998 ◽

Vol 42 (7) ◽

pp. 1659-1665 ◽

Cited By ~ 15

Author(s):

Kurt G. Naber ◽

Ursula Theuretzbacher ◽

Martina Kinzig ◽

Orlin Savov ◽

Fritz Sörgel

Keyword(s):

Oral Dose ◽

Healthy Volunteers ◽

Single Oral Dose ◽

E Coli ◽

Wide Range ◽

The Mean ◽

Bactericidal Activities ◽

Tract Infections ◽

Time Kill ◽

Randomized Crossover Study

ABSTRACT Twelve healthy volunteers participated in this randomized crossover study to compare the concentrations and recovery levels of fleroxacin and pefloxacin in urine and to assess their bactericidal activities against 12 strains of urinary pathogens with different susceptibilities over a wide range of MICs. The volunteers received a single oral dose of 400 mg of fleroxacin or 800 mg of pefloxacin. The mean cumulative renal excretion of unchanged fleroxacin,N-demethyl-fleroxacin, and N-oxide-fleroxacin accounted for 67, 7, and 6% of the total dose, respectively. The total urinary recovery of pefloxacin and the active metabolite norfloxacin was 34%. In the time-kill and the urinary bactericidal titer (UBT) studies, only the subjects’ urine not supplemented with broth was used. With most tested organisms and both quinolones it took more than 8 h to achieve a reduction in CFU of 99.9% (3 log units). Overall, there was a good correlation between UBTs and MICs for the strains. Against Escherichia coli ATCC 25922 the median UBTs were similar for both antibiotics and at least 1:8 for 96 h; against the E. coli strain for which the MIC was 0.5 μg/ml the UBT was at least 1:4 for 48 h. The UBTs of both drugs against Klebsiella pneumoniae were at least 1:16 for 72 h. The UBTs for Staphylococcus aureus (the MIC for which was 16 μg/ml) of both antibiotics were low, and in some of the samples, no bactericidal titers were observed. UBTs for Proteus mirabilis of pefloxacin are significantly higher than those of fleroxacin. For Pseudomonas aeruginosa the median UBTs were present for the 24-to-48-h interval. The same is true forEnterococcus faecalis. Against Staphylococcus saprophyticus, UBTs were present for at least 48 h with both quinolones. Overall, a single oral dose of 400 mg of fleroxacin exhibits UBTs comparable to those of 800 mg of pefloxacin. Therefore, it may be expected that half of the dose of fleroxacin gives comparable results in the treatment of urinary tract infections; this should be substantiated in comparative clinical trials.

Download Full-text