Effect of rifampicin pretreatment on the oral bioavailability of domperidone in healthy human volunteers

2015 ◽  
Vol 30 (4) ◽  
Author(s):  
Adukondalu Devandla ◽  
Shravan Kumar Yamsani ◽  
Madhusudan Rao Yamsani
Keyword(s):  
Compartmental Model ◽  
Pharmacokinetic Parameters ◽  
Serum Concentrations ◽  
Reverse Phase Hplc ◽  
Reverse Phase ◽  
Healthy Human ◽  
Once Daily ◽  
Treatment Conditions ◽  
Human Volunteers ◽  
Daily Dose

AbstractIncreased exsorption of domperidone was observed from different parts of the small intestine of the rat after pretreatment with rifampicin by the everted sac method. Based on theAfter an overnight fast, 20 mg domperidone was administered to the volunteers, either alone or after 6 days pretreatment with a once daily dose of 600 mg rifampicin. Serum concentrations of domperidone were estimated by reverse phase HPLC. Pharmacokinetic parameters were determined based on non-compartmental model analysis using the computer program kinetica.Rifampicin pretreatment decreased Cmax, AUCoThis interaction may have clinical significance when domperidone is co-administered with rifampicin in chronic treatment conditions, such as tuberculosis, leprosy and other infections of joints, bones, etc.

Nerve growth factor serum concentrations in healthy human volunteers: physiological variance and stability

2003 ◽  
Vol 344 (1) ◽  
pp. 13-16 ◽  
Author(s):  
Undine E. Lang ◽  
Jürgen Gallinat ◽  
Heidi Danker-Hopfe ◽  
Malek Bajbouj ◽  
Rainer Hellweg
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Serum Concentrations ◽  
Healthy Human ◽  
Nerve Growth ◽  
Human Volunteers

Once-Daily Dosing with Phenobarbital in Children with Seizure Disorders

PEDIATRICS ◽  
1981 ◽  
Vol 68 (6) ◽  
pp. 824-827
Author(s):  
Anne G. Davis ◽  
Kelly D. Mutchie ◽  
Joel A. Thompson ◽  
Garth G. Myers
Keyword(s):  
Adverse Reactions ◽  
Pediatric Patients ◽  
Seizure Activity ◽  
Single Daily Dose ◽  
Daily Regimen ◽  
Serum Concentrations ◽  
Once Daily ◽  
Seizure Disorders ◽  
Daily Dose

In nine pediatric patients with seizure disorders, aged 8 months to 16½ years, a single daily dose of phenobarbital was as effective in maintaining therapeutic serum concentrations as twice-daily dosing. There were no adverse reactions to the once-daily regimen, and no seizure activity occurred during the study as a result of the change in dosing pattern.

Molecular Characterization and Pharmacology of Epoetin Delta − The Only Erythropoietin Produced in a Human Cell Line.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1299-1299
Author(s):  
Raymond D. Pratt ◽  
J. Dowell ◽  
Z. Shahrokh ◽  
S. Flatman ◽  
M. Davies ◽  
...  
Keyword(s):  
Amino Acid ◽  
Adverse Events ◽  
Human Cell Line ◽  
Pharmacokinetic Parameters ◽  
Epoetin Alfa ◽  
Healthy Individuals ◽  
Reverse Phase Hplc ◽  
Reverse Phase ◽  
Dose Dependent ◽  
Serum Erythropoietin

Abstract Recombinant erythropoietins are used extensively in the management of anemia associated with chronic kidney disease (CKD). All the currently available erythropoietins are synthesized in Chinese hamster ovary (CHO) cell lines resulting in differences in glycosylation compared with human serum erythropoietin. We report the molecular characterization and pharmacokinetic properties of epoetin delta (Dynepo®, Shire plc), the only erythropoietin produced in a human cell line. A variety of techniques have been used to characterize epoetin delta, including amino acid sequencing, peptide mapping with reverse-phase HPLC/mass spectrometry, oligosaccharide profiling and MALDI-TOF of released glycans. Sialic acid and N-glycolylneuraminic acid (Neu5Gc) residues were quantified, following labeling of the released glycans, by reverse-phase HPLC analysis with fluorescence detection. Epoetin delta was produced as a highly pure and stable protein with the full human primary amino acid sequence. Neu5Gc residues were not detectable in epoetin delta within the validated limits of the assay but became readily detectable in CHO derived epoetins. Following characterization of the molecule early studies were done to determine the pharmacokinetic and pharmacodynamic properties of epoetin delta. Two studies investigated responses to epoetin delta in healthy individuals. The first study involved randomization of 21 men to either intravenous (i.v.) epoetin delta (15, 40 or 100 IU/kg) or placebo. The second was an open-label, crossover study, involving 32 volunteers randomized to receive single doses of epoetin delta 75 IU/kg given i.v. or subcutaneous (s.c.) by injection. Two further studies were carried out with CKD patients requiring hemodialysis who had previously received epoetin alfa. The first involved 40 patients randomized to epoetin delta or epoetin alfa (50 or 100 IU/kg), three-times per week for 4 weeks. The second was a single-dose study in 28 patients comparing epoetin delta 150 and 300 IU/kg given i.v. or s.c. Pharmacokinetic parameters were calculated from serum erythropoietin concentrations (determined by ELISA) by validated non-compartmental techniques using WinNonlin Professional v3.0A. Intravenous epoetin delta in healthy individuals displayed non-linear and dose-dependent pharmacokinetics, with a dose-dependent effect on serum hemoglobin. The bioavailability of s.c. epoetin delta is around 30%, and concentrations peak later and decline more slowly than with i.v. injection. In hemodialysis patients pharmacokinetic parameters were similar to those in healthy individuals, although AUC and half-life were increased. Compared with the 50 IU/kg dose, treatment with epoetin delta 100 IU/kg was associated with a trend to increased hemoglobin and hematocrit levels. Epoetin delta was well tolerated in all participants with the frequency of adverse events occurring in dialysis patients as expected for that population. Adverse events were similar with epoetin alfa and epoetin delta. No neutralizing anti-erythropoietin antibodies were detected in any patient. Epoetin delta was characterized at the molecular level and levels of Neu5Gc residues were undetectable within the validated limits of the assay. The pharmacokinetic profile of epoetin delta and effects on hemoglobin and hematocrit levels were suitable for the treatment of anemia in CKD patients by either s.c or i.v. administration.

Alternative Dosing Strategy for Aminoglycosides: Impact on Efficacy, Nephrotoxicity, and Ototoxicity

DICP ◽  
1989 ◽  
Vol 23 (10) ◽  
pp. 788-794 ◽  
Author(s):  
Gary L.C. Chan
Keyword(s):  
Renal Damage ◽  
Renal Cortex ◽  
Serum Concentrations ◽  
Postantibiotic Effect ◽  
Once Daily ◽  
Aminoglycoside Therapy ◽  
Daily Dose ◽  
Dosing Strategy ◽  
Tract Infections ◽  
Dosing Intervals

Accumulating evidence suggests that the therapeutic margin of aminoglycoside therapy may be improved by manipulation of dosing strategy. Recent understanding of concentration-dependent bactericidal activity and postantibiotic effect argues that the aminoglycosides may be administered in larger doses and at longer dosing intervals than currently recommended without compromising efficacy. Preliminary clinical experience suggests that once-daily regimens are as efficacious as conventional intermittent injections in the treatment of gram-negative infections including urinary tract infections, cystic fibrosis, and bacteremia in nonneutropenic patients. The transient, high peak serum concentrations achieved in once-daily dosing have not been associated with excessive nephrotoxicity or ototoxicity thus far. Decreased accumulation in renal cortex as a result of saturable renal uptake after the single daily dose may even reduce the incidence or severity of renal damage. Further studies on more patients are required to substantiate these preliminary findings.

scholarly journals A Liquid Chromatography-Tandem Mass Spectrometry Method for Evaluation of Two Brands of Enalapril 20 mg Tablets in Healthy Human Volunteers

2017 ◽  
Vol 2017 ◽  
pp. 1-8
Author(s):  
Wael Abu Dayyih ◽  
Mohammed Hamad ◽  
Ahmad Abu Awwad ◽  
Eyad Mallah ◽  
Zainab Zakarya ◽  
...  
Keyword(s):  
Enzyme Inhibitor ◽  
Internal Standard ◽  
Pharmacokinetic Parameters ◽  
Healthy Human ◽  
Chronic Heart Disease ◽  
Chromatography Tandem Mass Spectrometry ◽  
Human Volunteers ◽  
Treatment Of Hypertension ◽  
Liquid Chromatography Tandem Mass ◽  
Enalapril And Enalaprilat

Enalapril is an angiotensin-converting enzyme inhibitor used for treatment of hypertension and chronic heart disease. Enalaprilat is its active metabolite responsible for the activity. This study aimed to develop and validate a method for enalapril and enalaprilat analysis and to determine the bioequivalence of two tablet formulae of enalapril. LC-MS/MS bioanalytical method was developed and validated and then applied to evaluate the bioavailability of two enalapril formulae. Antihyperglycemic sitagliptin was used as internal standard (IS). The method was accurate for the within- and between-days analysis, and precise CV% was <5%, being linear over the calibration range 1.0–200.0 ng/ml. Stability was >85% and the LOD was 0.907 and 0.910 ng/ml for enalapril and enalaprilat, respectively, and LLOQ was 1 ng/ml. The pharmacokinetic parameters Cmax, tmax, AUC0–72, and AUC0–∞ values of enalapril and enalaprilat of the two formulae were calculated and nonsignificant differences were found. A linearity, specific, accurate, and precise method was developed and applied for the analysis of enalapril and enalaprilat in human plasma after oral administration of two formulae of enalapril 20 mg tablets in healthy volunteers. Depending on the statistical analysis it was concluded that the two enalapril formulae were bioequivalent.

Effect of silymarin pretreatment on the bioavailability of domperidone in healthy human volunteers

2014 ◽  
Vol 29 (4) ◽  
Author(s):  
Shravan Kumar Yamsani ◽  
Madhusudan Rao Yamsani
Keyword(s):  
Oral Bioavailability ◽  
Pharmacokinetic Parameters ◽  
Rat Intestine ◽  
Healthy Human ◽  
P Glycoprotein ◽  
Human Volunteers ◽  
Significant Difference

AbstractThe aim of this study was to investigate the effect of silymarin pretreatment on domperidone oral bioavailability in humans.The rats were pretreated with silymarin for 7 days. The transport of domperidone across the rat intestine (duodenum, jejunum, ileum, and colon) was studied by usingIn the everted sac and non-everted sac study with silymarin pretreatment, domperidone transport increased from the duodenum, jejunum, ileum, and colon. The silymarin pretreatment increased the bioavailability of domperidone. There was a statistically significant difference in the pharmacokinetic parameters CThe significant difference in absorption of domperidone on pretreatment with silymarin is due to the inhibition of P-glycoprotein and CYP3A. Silymarin, which inhibits CYP3A4, should be contraindicated for domperidone.

scholarly journals Vomiting is a Potential Adverse Drug Reaction for Levomilnacipran

2017 ◽  
Vol 9 (05) ◽  
Author(s):  
Atreyee Sarkar ◽  
Shivanand Dhanure
Keyword(s):  
Adverse Drug Reaction ◽  
Adverse Reaction ◽  
Extended Release ◽  
Pharmacokinetic Parameters ◽  
Regulatory Requirements ◽  
Healthy Human ◽  
Release Formulation ◽  
Extended Release Formulation ◽  
Human Volunteers ◽  
The Us

Levomilnacipran is a drug used to treat depression. Micro Labs is a generic drug company which had developed an extended release formulation of Levomilnacipran 120 mg capsule. Two studies were conducted to assess the safety, tolerability and bioequivalence of the extended release formulation of 120 mg Levomilnacipran capsules. A total of 42 subjects had been included for each of the fasting and fed studies. Out of them, 30 subjects completed the fasting study and 28 subjects completed the fed study. Pharmacokinetic parameters like Cmax, AUC0-t, AUC0-inf, Tmax, Kel, t1/2 and %AUCextra were calculated for Levomilnacipran in order to compare the bioavailability of the test and reference formulations. The studies were conducted in healthy human volunteers in both fasting and fed conditions as per the US regulatory requirements for conduct of bioequivalence studies. The formulations were found to be bioequivalent to each other. Vomiting was observed as a major adverse reaction.

scholarly journals Comparative Bioavailability of Four Marketed Sparfloxacin Formulations in Healthy Human Volunteers

2004 ◽  
Vol 1 (1) ◽  
pp. 43-50 ◽  
Author(s):  
K. Ravindra Rao ◽  
J. Vijaya Ratna ◽  
T. Manikya Rao
Keyword(s):  
Latin Square ◽  
Relative Bioavailability ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Data ◽  
Time Data ◽  
Time Intervals ◽  
Healthy Human ◽  
Human Volunteers ◽  
Comparative Bioavailability ◽  
Tablet Formulations

The objective of the study was to obtain the pharmacokinetic data of four marketed tablet formulations of sparfloxacin and compare the relative bioavailability of the formulations with standard formulation. A single dose 4×4 latin square design of the four marketed tablet formulations of sparfloxacin (200 mg) was carried out in four healthy male volunteers. Blood samples were collected at predetermined time intervals. The serum concentrations of the drug were determined by microbiological assay. The pharmacokinetic parameters were calculated from the plasma concentration of sparfloxacinversustime data. The AUC0-αof the sparfloxacin from products A, B, C and D was 23.33±3.90 μg h/mL, 19.72±2.47 μg h/mL, 18.76±5.19 μg h/mL and 18.27±2.84 μg h/mL respectively. The Cmaxand t1/2of the sparfloxacin was 0.98±0.07 μg/mL, 14.91±1.30 h, 0.80±0.06 μg/mL, 15.75±2.37 h, 0.78±0.11 μg/mL, 16.01±1.98 and 0.81±0.04 μg/mL, 13.91±3.59 h respectively for the products A, B, C and D. The serum concentration of the sparfloxacin and other pharmacokinetic parameters obtained were statistically analyzed. The results of three-way analysis of variance of serum drug levels and pharmacokinetic parameters showed that there was no significant variation between the products, subjects and treatments at all the points of time with regard to the AUC0-α,Cmaxand t1/2. The results of the study indicated that the products A, B, C and D are bioequivalent.

scholarly journals Plasma Analysis of Celiprolol by HPTLC: A Useful Technique for Pharmacokinetic Studies

2001 ◽  
Vol 84 (4) ◽  
pp. 1252-1257 ◽  
Author(s):  
Hema S Savale ◽  
Kalpesh K Pandya ◽  
Thakorbhai P Gandhi ◽  
Indravadan A Modi ◽  
Rajiv I Modi ◽  
...  
Keyword(s):  
High Performance ◽  
Extraction Procedure ◽  
Internal Standard ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Healthy Human ◽  
Direct Estimate ◽  
Plasma Analysis ◽  
Human Volunteers ◽  
Simple Extraction

Abstract A rapid and sensitive high performance, thin-layer chromatographic (HPTLC) method has been developed for the measurement of celiprolol in human plasma and its use in pharmacokinetic studies has been evaluated. Detection and quantitation were performed without using an internal standard. A simple extraction procedure was followed for extracting celiprolol from plasma and a known amount of the extract was spotted on precoated silica gel 60 F254 plates using a Camag Linomat IV autosampler. Celiprolol was quantitated using a Camag TLC Scanner 3. The average recovery of authentic analytes (20 to 200 ng/mL) added to plasma was 72.06 ± 2.8% and the lowest amount of celiprolol that could be detected was 10 ng/mL. The method provides a direct estimate of the amount of celiprolol present in plasma. Pharmacokinetic parameters of 2 marketed preparations have also been determined after oral administration to 12 healthy human volunteers.

Pharmacokinetic Evaluation of Two Brands of Linezolid Tablets in Healthy Human Volunteers

2010 ◽  
Vol 3 (2) ◽  
pp. 933-939
Author(s):  
Parameshwar P ◽  
Y N Rao ◽  
Shobha J C ◽  
Y N Reddy ◽  
V M Reddy
Keyword(s):  
Lower Limit ◽  
Bioequivalence Study ◽  
Hplc Method ◽  
Pharmacokinetic Parameters ◽  
Healthy Human ◽  
Blood Samples ◽  
Upper Limit ◽  
Human Volunteers ◽  
Significant Difference ◽  
Healthy Adult Male

The aim of a  randomized, balanced, two treatment, two-period, two-sequence, single-dose, crossover pilot bioavailability and bioequivalence study conducted in 12 healthy adult male volunteers under fasting conditions was to compare steady state pharmacokinetics of Linezolid 600mg tablets of Dr.Reddy’s Laboratories Ltd, and Zyvox ® (Linezolid) 600mg tablets of Pharmacia & Upjohn Company, USA. The subjects were dosed once during the study and the pre-dose blood samples were collected within 1 hr prior to dosing. The concentrations of Linezolid from the blood samples were quantified by validated HPLC method and pharmacokinetic parameters were computed. 90% Confidence intervals of reference Vs test for Cmax  lower limit 87.23 and upper limit 109.24, AUC0-t lower limit 86.20 and upper limit 109.17, AUCO-α lower limit 85.48 and upper limit 111.54. Analysis of variance (ANOVA) did not show significant difference to these parameters. Based on the results obtained, both the formulations have exhibited the same rate and extent of absorption, indicating switch ability in clinical practice.

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